Background:Hepatocellular carcinoma(HCC)is the fourth leading cause of cancer-related deaths globally.Splicing factor proline and glutamine-rich(SFPQ)is a multifunctional protein that controls various biological funct...Background:Hepatocellular carcinoma(HCC)is the fourth leading cause of cancer-related deaths globally.Splicing factor proline and glutamine-rich(SFPQ)is a multifunctional protein that controls various biological functions.As a potential therapeutic target and a promising prognostic indicator,the potential effects and processes of SFPQ in HCC require further investigation.Methods:The RNA sequencing data were obtained from the Gene Expression Omnibus,International Cancer Genome Consortium,and The Cancer Genome Atlas databases to analyze SFPQ expression and differentially expressed genes(DEGs).We utilized the LinkedOmics database to identify co-expressed genes.A Venn diagram was constructed to determine the overlapping genes between the DEGs and the co-expressed genes.Functional enrichment analysis was performed on the overlapping genes and DEGs.Furthermore,our study involved functional enrichment analysis,a protein-protein interaction network analysis,and an analysis of immune cell infiltration.The cBioPortal and Tumor Immune Single-cell Hub were utilized to investigate the genetic alterations of SFPQ and the single-cell transcriptome visualization of the tumor microenvironment.A ceRNA network was established with the assistance of the ENCORI website.Finally,we elucidated the clinical significance of SFPQ in HCC by employing Kaplan-Meier survival analysis,univariate and multivariate Cox regression,and prognostic nomogram models.Results:The expression of SFPQ in HCC tissues was significantly elevated compared to normal tissues.GSEA results indicated that increased expression of SFPQ was associated with pathways related to HCC.The ceRNA network,including SFPQ,hsa-miR-101-3p,AC023043.4,AC124798.1,AC145207.5,and GSEC,was constructed with the assistance of ENCORI.High SFPQ expression was related to a poor prognosis in HCC and its subtypes.Univariate and multivariate Cox regression analysis showed that elevated SFPQ expression is an independent predictive factor.Conclusions:The overexpression of SFPQ may serve as a potential prognostic biomarker,indicating a poor prognosis in HCC.展开更多
Background: The protein encoded by ring finger protein 157 (RNF157) is known to function as an E3 ubiquitinligase. However, whether the level of RNF157 expression in breast cancer correlates with prognosis and immune ...Background: The protein encoded by ring finger protein 157 (RNF157) is known to function as an E3 ubiquitinligase. However, whether the level of RNF157 expression in breast cancer correlates with prognosis and immune cellinfiltration among breast cancer patients remains to be further explored. Methods: In this study, publicly availabledatasets were used for evaluating RNF157 expression in different tumors compared with normal samples. Severalindependent datasets were screened for investigating the relationship between RNF157 and breast cancer survival,different mutation profiles, and tumor immune cell infiltration. We conducted a pathway enrichment analysis toidentify signaling pathways associated with RNF157. Results: Analysis of public and online databases revealed thatRNF157 expression markedly decreased in breast cancer tissue samples compared to non-carcinoma counterparts.Consistently, immunohistochemistry assays also demonstrated this RNF157 down-regulation in breast cancer samples.RNF157 up-regulation could predict the improved survival of breast cancer cases. Further, different RNF157expression level groups exhibited different mutational profiles. Pathway enrichment profiling of RNF157-related genessuggested its possible involvement in regulating breast cancer via the mitogen-activated protein kinase (MAPK)pathway. RNA sequencing (RNA-seq) data and genomic enrichment analysis showed that RNF157 downregulatedseveral genes positively associated with the MAPK signaling pathway. We also explored RNF157 expression andimmune cell infiltration in breast cancer and found that RNF157 mRNA levels were negatively related to non-Timmune cell infiltration. Conclusion: According to our work, RNF157 may be a promising diagnostic biomarker andtherapeutic target for breast cancer.展开更多
Enhancer of zeste homolog 2(EZH2)is the catalytic subunit of polycomb repressive complex 2(PRC2).Dysregulation of EZH2 causes alteration of gene expression and functions,thereby promoting cancer development.Recent stu...Enhancer of zeste homolog 2(EZH2)is the catalytic subunit of polycomb repressive complex 2(PRC2).Dysregulation of EZH2 causes alteration of gene expression and functions,thereby promoting cancer development.Recent studies suggest that EZH2 has a potential prognostic role in patients with nonsmall cell lung cancer(NSCLC).However,the prognostic value of EZH2 expression levels in NSCLC is controversial.In this study,we evaluated the prognostic value in lung cancer(LC-LUAD/LUSC)based on data from The Cancer Genome Atlas(TCGA)database.Kruskal-Wallis test,Wilcoxon signed-rank test,and logistic regression were used to evaluate the relationship between EZH2 expression and clinicopathological features.Cox regression and the Kaplan-Meier method were adopted to evaluate prognosis-related factors.Gene set enrichment analysis(GSEA)was performed to identify the key pathways related to EZH2.The correlations between EZH2 and cancer immune infiltrates were investigated by single-sample Gene Set Enrichment Analysis(ssGSEA).EZH2 was found to be up regulated with amplification in tumor tissues in multiple LC cohorts.High EZH2 expression was associated with poorer overall survival(OS).GSEA suggested that EZH2 regulates innate immune system,ECM affiliated,matrisome,surfactant metabolism.Notably,ssGSEA indicated that EZH2 expression was positively correlated with infiltrating levels of Th2 cells and significantly negatively correlated with mast cell infiltration level.These results suggest that EZH2 is associated with LC immune infiltration and significantly over-expressed in lung cancer,and its diagnostic value is better than prognosis,which lays a foundation for further study of the immunomodulatory role of EZH2 in LC.展开更多
Background:Lung cancer,particularly lung adenocarcinoma(LUAD),is highly lethal.Understanding the critical interaction between epithelial-mesenchymal transition(EMT)and the immune status of patients is imperative for c...Background:Lung cancer,particularly lung adenocarcinoma(LUAD),is highly lethal.Understanding the critical interaction between epithelial-mesenchymal transition(EMT)and the immune status of patients is imperative for clinical assessment.Methods:We conducted bioinformatics analysis to identify potential immune-related EMT(iEMT)prognostic genes and explored the immune status in LUAD.Using data from The CancerGenome Atlas andGSE68465,differentially expressed genes,were identified,and a risk modelwas constructed.Cluster analysis was conducted using the Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathways.Results:Our findings revealed 69 differentially expressed iEMT genes,with risk values demonstrating independent prognostic significance for both The Cancer Genome Atlas and GSE68465 samples.The risk value was positively correlated with tumor stage.Immune cell infiltration analysis showed a significant decrease in resting dendritic cells and an increase in CD4 memory T cells in high-risk groups with poor survival prognoses.The immunotherapy analysis revealed weak immunotherapeutic effects in the high-risk group.Conclusions:This study provides insights into potential aberrant differential iEMT genes and risk models and explores immune landscapes that inform personalized immunotherapy in patients with LUAD.展开更多
Background:Owing to the occurrence of primary or secondary tolerance,the efficacy of immunotherapy for hepatocellular carcinoma(HCC)patients is limited.Therefore,the mechanism underlying this tolerance needs to be fur...Background:Owing to the occurrence of primary or secondary tolerance,the efficacy of immunotherapy for hepatocellular carcinoma(HCC)patients is limited.Therefore,the mechanism underlying this tolerance needs to be further investigated.B cell–specific Moloney murine leukemia virus integration site 1(BMI1)is associated with cancer stem cell tumorigenesis,progression,and the maintenance of the self-renewal.However,the effect of BMI1 expression on immune infiltration and prognosis in HCC is still unclear.Methods:To assess the relationship between BMI1 expression and HCC prognosis and immune infiltration,the GEPIA database,TIMER database,and K-M plotter were used.TIMER database was used to determine the levels ofBMI1 in various tumor tissues and corresponding normal tissues,and examine the association between BMI1 expression and tumor-infiltrating immune cells.GEPIA database was applied to determine BMI1 expression in various tumor tissues and corresponding normal tissues.K-M Plotter was used to study the relationships among BMI1 expression,clinicopathological features,and survival rates.Results:BMI1 expression was markedly higher in various solid tumors compared with that in the respective normal tissues,including HCC,and high expression led to poor relapse-free survival and overall survival in HCC patients.BMI1 overexpression was also correlated with the infiltration of immune cells(eg,B cells,CD8+T cells,CD4+T cells,dendritic cells,neutrophils,and macrophages)and positively associated with different subsets of T cells,monocytes,and M1 macrophages,among others.Conclusions:This study demonstrates that high BMI1 expression is strongly correlated with immune infiltration and poor prognosis in HCC.Increased expression of BMI1 might thus be a potential mechanism of immune tolerance in this disease.展开更多
BACKGROUND Metadherin(MTDH)is a key oncogene in most cancer types,including hepato-cellular carcinoma(HCC).Notably,MTDH does not affect the stemness pheno-type or immune infiltration of HCC.AIM To explore the role of ...BACKGROUND Metadherin(MTDH)is a key oncogene in most cancer types,including hepato-cellular carcinoma(HCC).Notably,MTDH does not affect the stemness pheno-type or immune infiltration of HCC.AIM To explore the role of MTDH on stemness and immune infiltration in HCC.METHODS MTDH expression in HCC tissues was detected using TCGA and GEO databases.Immunohistochemistry was used to analyze the tissue samples.MTDH was stably knocked down or overexpressed by lentiviral transfection in the two HCC cell lines.The invasion and migration abilities of HCC cells were evaluated using Matrigel invasion and wound healing assays.Next,we obtained liver cancer stem cells from the spheroids by culturing them in a serum-free medium.Gene expression was determined by western blotting and quantitative reverse transcri-ption PCR.Flow cytometry,immunofluorescence,and tumor sphere formation assays were used to characterize stem-like cells.The effects of MTDH inhibition on tumor growth were evaluated in vivo.The correlation of MTDH with immune cells,immunomodulators,and chemokines was analyzed using ssGSEA and TISIDB databases.RESULTS HCC tissues expressed higher levels of MTDH than normal liver tissues.High MTDH expression was associated with a poor prognosis.HCC cells overex-pressing MTDH exhibited stronger invasion and migration abilities,exhibited a stem cell-like phenotype,and formed spheres;however,MTDH inhibition attenuated these effects.MTDH inhibition suppressed HCC progression and CD133 expression in vivo.MTDH was positively correlated with immature dendritic,T helper 2 cells,central memory CD8^(+)T,memory B,activated dendritic,natural killer(NK)T,NK,activated CD4^(+)T,and central memory CD4^(+)T cells.MTDH was negatively correlated with activated CD8^(+)T cells,eosinophils,activated B cells,monocytes,macrophages,and mast cells.A positive correlation was observed between the MTDH level and CXCL2 expression,whereas a negative correlation was observed between the MTDH level and CX3CL1 and CXCL12 expression.CONCLUSION High levels of MTDH expression in patients with HCC are associated with poor prognosis,promoting tumor stemness,immune infiltration,and HCC progression.展开更多
Hepatocellular carcinoma(HCC)is a malignancy known for its unfavorable prognosis.The dysregulation of the tumor microenvironment(TME)can affect the sensitivity to immunotherapy or chemotherapy,leading to treatment fai...Hepatocellular carcinoma(HCC)is a malignancy known for its unfavorable prognosis.The dysregulation of the tumor microenvironment(TME)can affect the sensitivity to immunotherapy or chemotherapy,leading to treatment failure.The elucidation of PHLDA2’s involvement in HCC is imperative,and the clinical value of PHLDA2 is also underestimated.Here,bioinformatics analysis was performed in multiple cohorts to explore the phenotype and mechanism through which PHLDA2 may affect the progression of HCC.Then,the expression and function of PHLDA2 were examined via the qRT-PCR,Western Blot,and MTT assays.Our findings indicate a substantial upregulation of PHLDA2 in HCC,correlated with a poorer prognosis.The methylation levels of PHLDA2 were found to be lower in HCC tissues compared to normal liver tissues.Besides,noteworthy associations were observed between PHLDA2 expression and immune infiltration in HCC.In addition,PHLDA2 upregulation is closely associated with stemness features and immunotherapy or chemotherapy resistance in HCC.In vitro experiments showed that sorafenib or cisplatin significantly up-regulated PHLDA2 mRNA levels,and PHLDA2 knockdown markedly decreased the sensitivity of HCC cells to chemotherapy drugs.Meanwhile,we found that TGF-βinduced the expression of PHLDA2 in vitro.The GSEA and in vitro experiment indicated that PHLDA2 may promote the HCC progression via activating the AKT signaling pathway.Our study revealed the novel role of PHLDA2 as an independent prognostic factor,which plays an essential role in TME remodeling and treatment resistance in HCC.展开更多
Background:IQGAP3 plays a crucial role in regulating cell proliferation,division,and cytoskeletal organization.Abnormal expression of IQGAP3 has been linked to various tumors,but its function in glioma is not well und...Background:IQGAP3 plays a crucial role in regulating cell proliferation,division,and cytoskeletal organization.Abnormal expression of IQGAP3 has been linked to various tumors,but its function in glioma is not well understood.Methods:Various methods,including genetic differential analysis,single-cell analysis,ROC curve analysis,Cox regression,Kaplan-Meier analysis,and enrichment analysis,were employed to analyze the expression patterns,diagnostic potential,prognostic implications,and biological processes involving IQGAP3 in normal and tumor tissues.The impact of IQGAP3 on immune infiltration and the immune microenvironment in gliomas was evaluated using immunofluorescence.Additionally,the cBioPortal database was used to analyze copy number variations and mutation sites of IQGAP3.Experimental validation was also performed to assess the effects of IQGAP3 on glioma cells and explore underlying mechanisms.Results:High IQGAP3 expression in gliomas is associated with an unfavorable prognosis,particularly in wild-type IDH and 1p/19q non-codeleted gliomas.Enrichment analysis revealed that IQGAP3 is involved in regulating the cell cycle,PI3K/AKT signaling,p53 signaling,and PLK1-related pathways.Furthermore,IQGAP3 expression may be closely related to the immunosuppressive microenvironment of glioblastoma.BRD-K88742110 and LY-303511 are potential drugs for targeting IQGAP3 in anti-glioma therapy.In vitro experiments showed that downregulation of IQGAP3 inhibits the proliferation and migration of glioma cells,with the PLK1/PI3K/AKT pathway potentially playing a crucial role in IQGAP3-mediated glioma progression.Conclusion:IQGAP3 shows promise as a valuable biomarker for diagnosis,prognosis,and immunotherapeutic strategies in gliomas.展开更多
Finding biomarkers for immunotherapy is an urgent issue in cancer treatment.Cellular retinoic acid-binding protein 2(CRABP2)is a controversial factor in the occurrence and development of human tumors.However,there is ...Finding biomarkers for immunotherapy is an urgent issue in cancer treatment.Cellular retinoic acid-binding protein 2(CRABP2)is a controversial factor in the occurrence and development of human tumors.However,there is limited research on the relationship between CRABP2 and immunotherapy response.This study found that negative correlations of CRABP2 and immune checkpoint markers(PD-1,PD-L1,and CTLA-4)were observed in breast invasive carcinoma(BRCA),skin cutaneous melanoma(SKCM),stomach adenocarcinoma(STAD)and testicular germ cell tumors(TGCT).In particular,in SKCM patients who were treated with PD-1 inhibitors,high levels of CRABP2 predicted poor prognosis.Additionally,CRABP2 expression was elevated in cancer-associated fibroblasts(CAFs)at the single-cell level.The expression of CRABP2 was positively correlated with markers of CAFs,such as MFAP5,PDPN,ITGA11,PDGFRα/βand THY1 in SKCM.To validate the tumor-promoting effect of CRABP2 in vivo,SKCM xenograft mice models with CRABP2 overexpression have been constructed.These models showed an increase in tumor weight and volume.Enrichment analysis indicated that CRABP2 may be involved in immunerelated pathways of SKCM,such as extracellular matrix(ECM)receptor interaction and epithelial-mesenchymal transition(EMT).The study suggests that CRABP2 may regulate immunotherapy in SKCM patients by influencing infiltration of CAFs.In conclusion,this study provides new insights into the role of CRABP2 in immunotherapy response.The findings suggest that CRABP2 may be a promising biomarker for PD-1 inhibitors in SKCM patients.Further research is needed to confirm these findings and to explore the clinical implications of CRABP2 in immunotherapy.展开更多
This research aims to identify the key fatty acid beta-oxidation(FAO)genes that are altered in kidney renal clear cell carcinoma(KIRC)and to analyze the role of these genes in KIRC The Gene Expression Omnibus(GEO)and ...This research aims to identify the key fatty acid beta-oxidation(FAO)genes that are altered in kidney renal clear cell carcinoma(KIRC)and to analyze the role of these genes in KIRC The Gene Expression Omnibus(GEO)and FAO datasets were used to identify these key genes.Wilcoxon rank sum test was used to assess the levels of acyl-CoA dehydrogenase medium chain(ACADM)between KIRC and non cancer samples.The logistic regression and Wilcoxon rank sum test were used to explore the association between ACADM and clinical features.The diagnostic performance of ACADM for KIRC was asessed using a diagnostic receiver operating ch aracteristic(ROC)curve.The co-expressed genes of ACADM were identifed in LinkedOmics database,and their function and pathway enrichment were analyzed.The correlation between ACADM expression level and immune infitration was analyzed by Gene Set Variation Analysis(GSVA)method Additionally,the proliferation,migration,and invasion abilities of KIRC cells were assessed after overexpressing ACADM.Following differential analysis and intersection,we identifed six hub genes,induding ACADM.We found that the expression level of ACADM was decreased in KIRC tissues and had a better diagnostic efect(AUC=0.916).Survival analysis suggested that patients with decreased ACADM expression had a worse prognosis.According to correlation analysis,a variety of dinical features were associated with the expression level of ACADML By analyzing the infiltration level of immune cells,we found that ACADM may be related to the enrichment of immune cells.Finally,ACADM overexpression inhibited proliferation,migration,and invasion of KIRC cells.In conclusion,our findings suggest that reduced ACADM expression in KIRC patients is indicative of poor prognosis.These results imply that ACADM may be a diagnostic and prognostic marker for individuals with KIRC,offering a reference for dinicians in diagnosis and treatment.展开更多
BACKGROUND Esophageal squamous cell carcinoma(ESCC)is one of the most common malignancies worldwide,and its development comprises a multistep process from intraepithelial neoplasia(IN)to carcinoma(CA).However,the crit...BACKGROUND Esophageal squamous cell carcinoma(ESCC)is one of the most common malignancies worldwide,and its development comprises a multistep process from intraepithelial neoplasia(IN)to carcinoma(CA).However,the critical regulators and underlying molecular mechanisms remain largely unknown.AIM To explore the genes and infiltrating immune cells in the microenvironment that are associated with the multistage progression of ESCC to facilitate diagnosis and early intervention.METHODS A mouse model mimicking the multistage development of ESCC was established by providing warter containing 4-nitroquinoline 1-oxide(4NQO)to C57BL/6 mice.Moreover,we established a control group without 4NQO treatment of mice.Then,transcriptome sequencing was performed for esophageal tissues from patients with different pathological statuses,including low-grade IN(LGIN),high-grade IN(HGIN),and CA,and controlled normal tissue(NOR)samples.Differentially expressed genes(DEGs)were identified in the LGIN,HGIN,and CA groups,and the biological functions of the DEGs were analyzed via Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses.The CIBERSORT algorithm was used to detect the pattern of immune cell infilt-ration.Immunohistochemistry(IHC)was also conducted to validate our results.Finally,the Luminex multiplex cytokine analysis was utilized to measure the serum cytokine levels in the mice.RESULTS Compared with those in the NOR group,a total of 681541,and 840 DEGs were obtained in the LGIN,HGIN,and CA groups,respectively.Using the intersection of the three sets of DEGs,we identified 86 genes as key genes involved in the development of ESCC.Enrichment analysis revealed that these genes were enriched mainly in the keratinization,epidermal cell differentiation,and interleukin(IL)-17 signaling pathways.CIBERSORT analysis revealed that,compared with those in the NOR group,M0 and M1 macrophages in the 4NQO group showed stronger infiltration,which was validated by IHC.Serum cytokine analysis revealed that,compared with those in the NOR group,IL-1βand IL-6 were upregulated,while IL-10 was downregulated in the LGIN,HGIN,and CA groups.Moreover,the expression of the representative key genes,such as S100a8 and Krt6b,was verified in external human samples,and the results of immunohistochemical staining were consistent with the findings in mice.CONCLUSION We identified a set of key genes represented by S100a8 and Krt6b and investigated their potential biological functions.In addition,we found that macrophage infiltration and abnormal alterations in the levels of inflam-mation-associated cytokines,such as IL-1β,IL-6,and IL-10,in the peripheral blood may be closely associated with the development of ESCC.展开更多
BACKGROUND Diabetic cardiomyopathy(DCM)is a multifaceted cardiovascular disorder in which immune dysregulation plays a pivotal role.The immunological molecular mechanisms underlying DCM are poorly understood.AIM To ex...BACKGROUND Diabetic cardiomyopathy(DCM)is a multifaceted cardiovascular disorder in which immune dysregulation plays a pivotal role.The immunological molecular mechanisms underlying DCM are poorly understood.AIM To examine the immunological molecular mechanisms of DCM and construct diagnostic and prognostic models of DCM based on immune feature genes(IFGs).METHODS Weighted gene co-expression network analysis along with machine learning methods were employed to pinpoint IFGs within bulk RNA sequencing(RNA-seq)datasets.Single-sample gene set enrichment analysis(ssGSEA)facilitated the analysis of immune cell infiltration.Diagnostic and prognostic models for these IFGs were developed and assessed in a validation cohort.Gene expression in the DCM cell model was confirmed through real time-quantitative polymerase chain reaction and western blotting techniques.Additionally,single-cell RNA-seq data provided deeper insights into cellular profiles and interactions.RESULTS The overlap between 69 differentially expressed genes in the DCM-associated module and 2483 immune genes yielded 7 differentially expressed immune-related genes.Four IFGs showed good diagnostic and prognostic values in the validation cohort:Proenkephalin(Penk)and retinol binding protein 7(Rbp7),which were highly expressed,and glucagon receptor and inhibin subunit alpha,which were expressed at low levels in DCM patients(all area under the curves>0.9).SsGSEA revealed that IFG-related immune cell infiltration primarily involved type 2 T helper cells.High expression of Penk(P<0.0001)and Rbp7(P=0.001)was detected in cardiomyocytes and interstitial cells and further confirmed in a DCM cell model in vitro.Intercellular events and communication analysis revealed abnormal cellular phenotype transformation and signaling communication in DCM,especially between mesenchymal cells and macrophages.CONCLUSION The present study identified Penk and Rbp7 as potential DCM biomarkers,and aberrant mesenchymal-immune cell phenotype communication may be an important aspect of DCM pathogenesis.展开更多
Background:This study aims to explore the involvement of ferroptosis-related genes and pathogenesis in pancreatic cancer and predict potential therapeutic interventions using Traditional Chinese Medicine(TCM).Methods:...Background:This study aims to explore the involvement of ferroptosis-related genes and pathogenesis in pancreatic cancer and predict potential therapeutic interventions using Traditional Chinese Medicine(TCM).Methods:We utilized gene expression datasets,ferroptosis upregulated genes and applied machine learning algorithms,including LASSO and SVM-RFE,to identify key ferroptosis-related genes in pancreatic cancer.Perform Gene Ontology,Kyoto Encyclopedia of Genes and Genomes,and Disease Ontology enrichment analysis,immune infiltration analysis and correlation analysis between immune infiltrating cells and characteristic genes on differentially expressed genes using the R software package.Retrieve potential traditional Chinese medicine for targeted ferroptosis gene therapy for pancreatic cancer through Coremine and Herb databases.Results:Seventeen feature genes were identified,with significant implications for immune cell infiltration in pancreatic cancer.The results of immune cell infiltration analysis showed that B cells naive,B cells memory,T cells regulatory,and M0 macrophages were significantly upregulated in pancreatic cancer patients;Mast cells resting were significantly downregulated.Chinese herbal medicines such as ginkgo,turmeric,ginseng,Codonopsis pilosula,Zedoary turmeric,deer tendons,senna leaves,Guanmu Tong,Huangqi,and Banzhilian are potential drugs for targeted ferroptosis gene therapy for pancreatic cancer.Conclusion:TIMP1 emerged as a key gene,with several TCM herbs predicted to modulate its expression,offering new avenues for treatment.展开更多
Background: A major cause of cancer death worldwide is bladder cancer, which is the most common malignant tumor of the urinary tract. PAEP is a member of the kernel lipocalin superfamily whose members share relatively...Background: A major cause of cancer death worldwide is bladder cancer, which is the most common malignant tumor of the urinary tract. PAEP is a member of the kernel lipocalin superfamily whose members share relatively low sequence similarity but have highly conserved exon/intron structure and three-dimensional protein folding. Most lipocalins are clustered on the long arm of chromosome 9. The purpose of this study was to clarify the correlation between PAEP expression level and bladder cancer. Methods: In the TCGA database, we obtained clinical and RNA sequencing data of 431 BLCA patients, including 412 BLCA tissues and 19 normal bladder tissues in the study. Analyses of bioinformatics were conducted in this study to determine the role of PAEP in bladder cancer. A quantitative real-time PCR method was used to quantitate the gene expression profile. Additionally, the effect of PAEP on tumor immune infiltration and prognosis was analyzed. Results: PAEP was a poor prognostic biomarker of bladder cancer because it was significantly upregulated. bladder cancer patients with higher PAEP expression had poor outcomes. An AUC of 0.780 was calculated from the area under the ROC curve. PAEP was associated with T stage, pathologic stage, Histologic grade and Subtype of bladder cancer patients, and served as an independent predictor of overall survival in bladder cancer patients. Functional enrichment analysis revealed PAEP was obviously enriched in pathways connected with carcinogenesis and immunosuppression. The expression of PAEP was significantly associated with tumor immune cells and immune checkpoints according to ssGSEA and Spearman correlation analysis. Conclusions: In this study, we screened and detected a mRNA, PAEP is a prognostic and immune-related biomarker in BLCA, which may contribute to the early diagnosis and treatment of BLCA.展开更多
Background:The molecular mechanism underlying the involvement of the Transferrin receptor(TFRC)in cervical cancer remains poorly understood.This study aims to elucidate the role of TFRC in cervical cancer by analyzing...Background:The molecular mechanism underlying the involvement of the Transferrin receptor(TFRC)in cervical cancer remains poorly understood.This study aims to elucidate the role of TFRC in cervical cancer by analyzing data from The Cancer Genome Atlas(TCGA)and Genotype-Tissue Expression(GTEx)databases.Methods:TFRC protein expression was obtained from Human Protein Altas(HPA).All datas were collected from TCGA and GTEx.In this study,we analyzed the expression of TFRC in cervical cancer and its clinical significance.Through Kyoto Encyclopedia of Genes and Genomes(KEGG)and Gene set enrichment analyses(GSEA),investigated the related molecular pathways of TFRC.The relationship between TFRC and immune infiltration was then examined.The prognosis of different immune cell subsets was then analyzed after dividing cervical cancer patients into high and low expression of TFRC groups.Results:TFRC is highly expressed in various tumor tissues compared to control normal tissues,including cervical cancer.An increased expression of TFRC was associated with higher Tumor(T)and Node(N)stage,as well as a higher clinical stage.Kaplan–Meier(KM)survival analysis investigated that higher TFRC expression patients have a poor overall survival(OS),disease specific survival(DSS)and progress free interval(PFI).Both KEGG and GSEA enriched signaling pathway by high TFRC and low TFRC groups.There was a significant negative linear correlation between TFRC expression and immune infiltration.TFRC affects the prognosis of cervical cancer patients through immune pathway.Conclusions:Cervical cancer patients with TFRC expression may have a worse prognosis.展开更多
Background:Hepatocellular carcinoma(HCC)is a leading cause of cancer-related death worldwide.The development of biomarkers for early detection and monitoring of HCC has not shown significant prog-ress.Meanwhile,the se...Background:Hepatocellular carcinoma(HCC)is a leading cause of cancer-related death worldwide.The development of biomarkers for early detection and monitoring of HCC has not shown significant prog-ress.Meanwhile,the second adenomatous polyposis-related gene,MUTYH,which encodes a DNA gly-cosylase,has been observed in its contribution to oxidative DNA damage repair.Abnormal expression of MUTYH can reduce cell survival rate.Therefore,this study investigated the usefulness of MUTYH in diagnosing and prognosis HCC.Materials and methods:Using The Cancer Genome Atlas(TCGA)data,we analyzed the prognostic value of MUTYH in HCC.We used logistic regression,Wilcoxon signed-rank test,and KruskaleWallis test to examine MUTYH expression concerning clinical-pathologic characteristics.Univariate and multivariate Cox regression methods and Kaplan-Meier analysis were applied to determine the related prognostic factors of HCC.The enrichment analysis(GSEA)was used to determine the critical pathways associated with MUTYH.The single-sample gene set enrichment analysis(ssGSEA)was conducted to examine the correlation between MUTYH expression and cancer immune infiltration.Results:The higher expression of MUTYH in HCC patients was associated with a poorer overall survival rate and a shorter disease-specific survival rate.The Kyoto Encyclopedia of Genes and Genomes(KEGG)analysis showed that all differentially expressed genes(DEGs)between the high and low expression levels of MUTYH significantly enriched in the trace ligand-receptor interaction,cell cycle,oocyte meiosis,gap junction,and DNA replication.Group analysis revealed the signals of their open access.The neuron system,M phase,DNA repair,Rho GTPase effector,and cell cycle checkpoints were significantly enriched.ssGSEA showed a positive correlation between MUTYH expression and the infiltration levels of Th2 cells,NK cells,and T helper cells.Moreover,a negative correlation was found between MUTYH expression and the infiltration levels of dendritic cells(DCs)and cytotoxic cells.Conclusions:MUTYH expression levels were positively correlated with immune checkpoint gene expression levels in HCC tissues.The expression level of MUTYH was related to the prognosis of HCC and the immune infiltration of HCC.展开更多
Objective:Most patients with advanced lung cancer have a poor prognosis.Recent studies have identified TRIM59 as a novel molecule that serves as a prognostic factor for the progression of non-small cell lung cancer.In...Objective:Most patients with advanced lung cancer have a poor prognosis.Recent studies have identified TRIM59 as a novel molecule that serves as a prognostic factor for the progression of non-small cell lung cancer.In the present study,we investigated the role of TRIM59 in predicting the prognosis of lung adenocarcinoma(LUAD)as well as the correlation between TRIM59 expression and immune infiltrates.Methods:We analyzed TRIM59 expression in normal and tumor tissues based on RNA-sequencing datasets from The Cancer Genome Atlas and Genotype-Tissue Expression databases.Forty-seven cases of LUAD tissues and their matching adjacent tissues were collected,and TRIM59 expression in tissue samples was demonstrated by immunohistochemistry.All tissue specimens were obtained under the approval of the Medical Ethics Committee of the Second Affiliated Hospital of Zhejiang University School of Medicine(approval No.IR2019001101;approved on April 3,2019).The immune cell scores were calculated using the CIBERSORT database.The Tumor Immune Estimation Resource database was used to analyze the correlation between TRIM59 and immune cell activities.Results:TRIM59 was up-regulated in most cancer types.High TRIM59 expression predicted a worse prognosis in patients with LUAD(overall survival,P=0.00096;disease-specific survival,P=0.00056;disease-free interval,P=0.0009;progression-free interval,P=0.0012).Moreover,TRIM59 was highly expressed in patients with LUAD who had a poorer prognosis.TRIM59 also showed a significant correlation with the ESTIMATE score(P=0.04)and stromal score(P=0.005)in patients with LUAD.Notably,a significant correlation between TRIM59 and the tumor mutation burden was found in LUAD but in no other cancer types(P<0.001).Further investigation showed that TRIM59 had a significant correlation with gene markers on neutrophils and dendritic cells.Conclusion:TRIM59 is a potential prognosticator in LUAD and may be correlated with immune cell identification,immune cell infiltration,and immunotherapy checkpoints in LUAD.展开更多
Background:Cytochrome b561(CYB561)plays a critical role in neuroendocrine function,cardiovascular regulation,and tumor growth;however,the prognostic value of CYB561 in patients with breast cancer and the relationship ...Background:Cytochrome b561(CYB561)plays a critical role in neuroendocrine function,cardiovascular regulation,and tumor growth;however,the prognostic value of CYB561 in patients with breast cancer and the relationship between CYB561 expression and immune infiltration in breast cancer remain unclear.Methods:The mRNA expression and clinical data of patients with breast cancer were obtained from The Cancer Genome Atlas database.Functional enrichment analysis was used to explore underlying biological functions associated with CYB561.The methylation status of CYB561 was analyzed using the MethSurv database.The enrichment score of immune cell infiltration for CYB561 in breast cancer was calculated using single-sample gene set enrichment analysis.The prognostic value of CYB561 was evaluated using Kaplan-Meier method and Cox regression analysis.Based on the results of the multivariate Cox analysis,a nomogram was constructed to predict the effect of CYB561 expression on overall survival(OS).Results:The results showed that CYB561 was highly expressed in breast cancer tissues.Hypomethylation of CYB561 is associated with an unfavorable prognosis.In multivariate Cox regression analysis,CYB561 was an independent prognostic factor for OS.Functional enrichment analysis indicated that estrogen signaling pathway,inflammatory response,KRAS signaling pathway,epithelial-mesenchymal transition,leukocyte migration,and regulation of lymphocyte activation were strongly enriched in the low CYB561 expression group.Additionally,CYB561 expression was negatively correlated with immune infiltration of B cells,plasmacytoid dendritic cells,dendritic cells,and neutrophils.Conclusion:CYB561 may serve as a potential biomarker for breast cancer diagnosis and prognosis.展开更多
BACKGROUND Immune cells play an important role in regulating the behavior of tumor cells.According to emerging evidence,six-transmembrane epithelial antigen of the prostate 4(STEAP4)performs a crucial part in tumor mi...BACKGROUND Immune cells play an important role in regulating the behavior of tumor cells.According to emerging evidence,six-transmembrane epithelial antigen of the prostate 4(STEAP4)performs a crucial part in tumor microenvironmental immune response and tumorigenesis,and serves as the potential target for cellular and antibody immunotherapy.However,the immunotherapeutic role of STEAP4 in gastric cancer(GC)remains unclear.AIM To investigate the expression of STEAP4 in GC and its relationship with immune infiltrating cells,and explore the potential value of STEAP4 as an immune prognostic indicator in GC.METHODS The expression level of STEAP4 was characterized by immunohistochemistry in tumors and adjacent non-cancerous samples in 96 GC patients.Tumor Immune Estimation Resource was used to study the correlation between STEAP4 and tumor immune infiltration level and immune infiltration gene signature.R package was used to analyze the relationship between STEAP4 expression and immune and stromal scores in GC(GSE62254)by the ESTIMATE algorithm,and Kaplan-Meier Plotter and Gene Expression Profiling Interactive Analysis were applied to analyze the effect of STEAP4 on clinical prognosis.RESULTS Immunohistochemistry analysis showed that STEAP4 expression was higher in GC tissues than in adjacent tissues,and STEAP4 expression was positively correlated with the clinical stage of GC.In GC,the expression of STEAP4 was positively correlated with the infiltration levels of B cells,CD4+T cells,macrophages,neutrophils,and dendritic cells.The expression level of STEAP4 was strongly correlated with most of the immune markers.In addition,STEAP4 expression was inversely correlated with tumor purity,but correlated with stromal score(r=0.43,P<0.001),immune score(r=0.29,P<0.001)and estimate score(r=0.39,P<0.001).Moreover,stromal,immune,and estimate scores were higher in the STEAP4 high expression group,whereas tumor purity was higher in the STEAP4 Low expression group.The relationship between STEAP4 expression and prognosis of patients with GC was further investigated,and the results showed that high STEAP4 expression was associated with poor overall survival and disease-free survival.In addition,Kaplan-Meier Plotter showed that high expression of STEAP4 was significantly correlated with poor survival of patients with GC.CONCLUSION The current findings suggest an oncogenic role for STEAP4 in GC,with significantly high levels being associated with poor prognosis.Investigation of the GC tumor microenvironment suggests the potential function of STEAP4 is connected with the infiltration of diverse immune cells,which may contribute to the regulation of the tumor microenvironment.In conclusion,STEAP4 may serve as a potential therapeutic target for GC to improve the immune infiltration,as well as serve as a prognostic biomarker for judging the prognosis and immune infiltration status of GC.展开更多
BACKGROUND Intrahepatic cholangiocarcinoma(ICC)is a malignant tumor of the hepatobiliary system with concealed onset,strong invasiveness and poor prognosis.AIM To explore the disease characteristic genes that may be h...BACKGROUND Intrahepatic cholangiocarcinoma(ICC)is a malignant tumor of the hepatobiliary system with concealed onset,strong invasiveness and poor prognosis.AIM To explore the disease characteristic genes that may be helpful in the diagnosis of ICC and affect immune cell infiltration.METHODS We downloaded two ICC-related human gene expression profiles from GEO database as the training group(GSE26566 and GSE32958 datasets)for difference analysis,and performed enrichment analysis on differential genes.The least absolute shrinkage and selection operator(LASSO),support vector machinerecursive feature elimination(SVM-RFE)and random forest(RF),three machine learning algorithms,were used to screen the characteristic genes.Double verification was carried out on GSE107943 and The Cancer Genome Atlas,two verification groups.Receiver operating characteristic curve and area under the curve(AUC)were used to evaluate the diagnostic efficacy of genes for ICC.CIBERSORT and ssGSEA algorithms were used to evaluate the effect of characteristic genes on immune infiltration pattern.Human Protein Atlas(HPA)was used to analyze the protein expression level of the target gene.RESULTS A total of 1091 differential genes were obtained in the training group.Enrichment analysis showed that the above genes were mainly enriched in small molecular catabolism,complement and coagulation cascade,bile secretion and other functions and pathways.Twentyfive characteristic genes were screened by LASSO regression,19 by SVM-RFE algorithm,and 30 by RF algorithm.Three algorithms were used in combination to determine the characteristic gene of ICC:MMP14.The verification group confirmed that the genes had a high diagnostic accuracy(AUC values of the training group and the verification group were 0.960,0.999,and 0.977,respectively).Comprehensive analysis of immune infiltration showed that MMP14 could affect the infiltration of monocytes,activated memory CD4 T cells,resting memory CD4 T cells,and other immune cells,and was closely related to the expression of CD200,cytotoxic T-lymphocyteassociated antigen 4,CD14,CD44,and other immune checkpoints.The results of immunohistochemistry in HPA database showed was indeed overexpressed in ICC.CONCLUSION MMP14 can be used as a disease characteristic gene of ICC,and may regulate the distribution of immune-infiltrating cells in the ICC tumor microenvironment,which provides a new method for the determination of ICC diagnostic markers and screening of therapeutic targets.展开更多
文摘Background:Hepatocellular carcinoma(HCC)is the fourth leading cause of cancer-related deaths globally.Splicing factor proline and glutamine-rich(SFPQ)is a multifunctional protein that controls various biological functions.As a potential therapeutic target and a promising prognostic indicator,the potential effects and processes of SFPQ in HCC require further investigation.Methods:The RNA sequencing data were obtained from the Gene Expression Omnibus,International Cancer Genome Consortium,and The Cancer Genome Atlas databases to analyze SFPQ expression and differentially expressed genes(DEGs).We utilized the LinkedOmics database to identify co-expressed genes.A Venn diagram was constructed to determine the overlapping genes between the DEGs and the co-expressed genes.Functional enrichment analysis was performed on the overlapping genes and DEGs.Furthermore,our study involved functional enrichment analysis,a protein-protein interaction network analysis,and an analysis of immune cell infiltration.The cBioPortal and Tumor Immune Single-cell Hub were utilized to investigate the genetic alterations of SFPQ and the single-cell transcriptome visualization of the tumor microenvironment.A ceRNA network was established with the assistance of the ENCORI website.Finally,we elucidated the clinical significance of SFPQ in HCC by employing Kaplan-Meier survival analysis,univariate and multivariate Cox regression,and prognostic nomogram models.Results:The expression of SFPQ in HCC tissues was significantly elevated compared to normal tissues.GSEA results indicated that increased expression of SFPQ was associated with pathways related to HCC.The ceRNA network,including SFPQ,hsa-miR-101-3p,AC023043.4,AC124798.1,AC145207.5,and GSEC,was constructed with the assistance of ENCORI.High SFPQ expression was related to a poor prognosis in HCC and its subtypes.Univariate and multivariate Cox regression analysis showed that elevated SFPQ expression is an independent predictive factor.Conclusions:The overexpression of SFPQ may serve as a potential prognostic biomarker,indicating a poor prognosis in HCC.
基金funded by the Innovation Team Project of Hainan Natural Science Foundation(820CXTD446)the Technology Program of Qingyuan(No.2022KJJH027 to Linhai Li).
文摘Background: The protein encoded by ring finger protein 157 (RNF157) is known to function as an E3 ubiquitinligase. However, whether the level of RNF157 expression in breast cancer correlates with prognosis and immune cellinfiltration among breast cancer patients remains to be further explored. Methods: In this study, publicly availabledatasets were used for evaluating RNF157 expression in different tumors compared with normal samples. Severalindependent datasets were screened for investigating the relationship between RNF157 and breast cancer survival,different mutation profiles, and tumor immune cell infiltration. We conducted a pathway enrichment analysis toidentify signaling pathways associated with RNF157. Results: Analysis of public and online databases revealed thatRNF157 expression markedly decreased in breast cancer tissue samples compared to non-carcinoma counterparts.Consistently, immunohistochemistry assays also demonstrated this RNF157 down-regulation in breast cancer samples.RNF157 up-regulation could predict the improved survival of breast cancer cases. Further, different RNF157expression level groups exhibited different mutational profiles. Pathway enrichment profiling of RNF157-related genessuggested its possible involvement in regulating breast cancer via the mitogen-activated protein kinase (MAPK)pathway. RNA sequencing (RNA-seq) data and genomic enrichment analysis showed that RNF157 downregulatedseveral genes positively associated with the MAPK signaling pathway. We also explored RNF157 expression andimmune cell infiltration in breast cancer and found that RNF157 mRNA levels were negatively related to non-Timmune cell infiltration. Conclusion: According to our work, RNF157 may be a promising diagnostic biomarker andtherapeutic target for breast cancer.
基金Supported by a grant from the Qingdao 2020 Medical Scientific Research Guidance Plan(No.2020-WJZD036).
文摘Enhancer of zeste homolog 2(EZH2)is the catalytic subunit of polycomb repressive complex 2(PRC2).Dysregulation of EZH2 causes alteration of gene expression and functions,thereby promoting cancer development.Recent studies suggest that EZH2 has a potential prognostic role in patients with nonsmall cell lung cancer(NSCLC).However,the prognostic value of EZH2 expression levels in NSCLC is controversial.In this study,we evaluated the prognostic value in lung cancer(LC-LUAD/LUSC)based on data from The Cancer Genome Atlas(TCGA)database.Kruskal-Wallis test,Wilcoxon signed-rank test,and logistic regression were used to evaluate the relationship between EZH2 expression and clinicopathological features.Cox regression and the Kaplan-Meier method were adopted to evaluate prognosis-related factors.Gene set enrichment analysis(GSEA)was performed to identify the key pathways related to EZH2.The correlations between EZH2 and cancer immune infiltrates were investigated by single-sample Gene Set Enrichment Analysis(ssGSEA).EZH2 was found to be up regulated with amplification in tumor tissues in multiple LC cohorts.High EZH2 expression was associated with poorer overall survival(OS).GSEA suggested that EZH2 regulates innate immune system,ECM affiliated,matrisome,surfactant metabolism.Notably,ssGSEA indicated that EZH2 expression was positively correlated with infiltrating levels of Th2 cells and significantly negatively correlated with mast cell infiltration level.These results suggest that EZH2 is associated with LC immune infiltration and significantly over-expressed in lung cancer,and its diagnostic value is better than prognosis,which lays a foundation for further study of the immunomodulatory role of EZH2 in LC.
基金Supported by grants from the National Natural Science Foundation of China(no.82001785)Chinese Society of Clinical Oncology(CSCO)-HengruiOncology Research Fund(No.Y-HR2020QN-0946).
文摘Background:Lung cancer,particularly lung adenocarcinoma(LUAD),is highly lethal.Understanding the critical interaction between epithelial-mesenchymal transition(EMT)and the immune status of patients is imperative for clinical assessment.Methods:We conducted bioinformatics analysis to identify potential immune-related EMT(iEMT)prognostic genes and explored the immune status in LUAD.Using data from The CancerGenome Atlas andGSE68465,differentially expressed genes,were identified,and a risk modelwas constructed.Cluster analysis was conducted using the Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathways.Results:Our findings revealed 69 differentially expressed iEMT genes,with risk values demonstrating independent prognostic significance for both The Cancer Genome Atlas and GSE68465 samples.The risk value was positively correlated with tumor stage.Immune cell infiltration analysis showed a significant decrease in resting dendritic cells and an increase in CD4 memory T cells in high-risk groups with poor survival prognoses.The immunotherapy analysis revealed weak immunotherapeutic effects in the high-risk group.Conclusions:This study provides insights into potential aberrant differential iEMT genes and risk models and explores immune landscapes that inform personalized immunotherapy in patients with LUAD.
基金the Natural Science Foundation of Shaanxi Province(Youth Projectno.2021JQ-423)the foundation of the Second Affiliated Hospital of Xi'an Jiaotong University(no.RC(XM)201706)。
文摘Background:Owing to the occurrence of primary or secondary tolerance,the efficacy of immunotherapy for hepatocellular carcinoma(HCC)patients is limited.Therefore,the mechanism underlying this tolerance needs to be further investigated.B cell–specific Moloney murine leukemia virus integration site 1(BMI1)is associated with cancer stem cell tumorigenesis,progression,and the maintenance of the self-renewal.However,the effect of BMI1 expression on immune infiltration and prognosis in HCC is still unclear.Methods:To assess the relationship between BMI1 expression and HCC prognosis and immune infiltration,the GEPIA database,TIMER database,and K-M plotter were used.TIMER database was used to determine the levels ofBMI1 in various tumor tissues and corresponding normal tissues,and examine the association between BMI1 expression and tumor-infiltrating immune cells.GEPIA database was applied to determine BMI1 expression in various tumor tissues and corresponding normal tissues.K-M Plotter was used to study the relationships among BMI1 expression,clinicopathological features,and survival rates.Results:BMI1 expression was markedly higher in various solid tumors compared with that in the respective normal tissues,including HCC,and high expression led to poor relapse-free survival and overall survival in HCC patients.BMI1 overexpression was also correlated with the infiltration of immune cells(eg,B cells,CD8+T cells,CD4+T cells,dendritic cells,neutrophils,and macrophages)and positively associated with different subsets of T cells,monocytes,and M1 macrophages,among others.Conclusions:This study demonstrates that high BMI1 expression is strongly correlated with immune infiltration and poor prognosis in HCC.Increased expression of BMI1 might thus be a potential mechanism of immune tolerance in this disease.
基金National Natural Science Foundation of China,No.82173359Basic Research and Frontier Exploration Project of Chongqing and Technology Commission,No.cstc2018jcyjAX0181Kuanren Talents Program of The Second Affiliated Hospital of Chongqing Medical University.
文摘BACKGROUND Metadherin(MTDH)is a key oncogene in most cancer types,including hepato-cellular carcinoma(HCC).Notably,MTDH does not affect the stemness pheno-type or immune infiltration of HCC.AIM To explore the role of MTDH on stemness and immune infiltration in HCC.METHODS MTDH expression in HCC tissues was detected using TCGA and GEO databases.Immunohistochemistry was used to analyze the tissue samples.MTDH was stably knocked down or overexpressed by lentiviral transfection in the two HCC cell lines.The invasion and migration abilities of HCC cells were evaluated using Matrigel invasion and wound healing assays.Next,we obtained liver cancer stem cells from the spheroids by culturing them in a serum-free medium.Gene expression was determined by western blotting and quantitative reverse transcri-ption PCR.Flow cytometry,immunofluorescence,and tumor sphere formation assays were used to characterize stem-like cells.The effects of MTDH inhibition on tumor growth were evaluated in vivo.The correlation of MTDH with immune cells,immunomodulators,and chemokines was analyzed using ssGSEA and TISIDB databases.RESULTS HCC tissues expressed higher levels of MTDH than normal liver tissues.High MTDH expression was associated with a poor prognosis.HCC cells overex-pressing MTDH exhibited stronger invasion and migration abilities,exhibited a stem cell-like phenotype,and formed spheres;however,MTDH inhibition attenuated these effects.MTDH inhibition suppressed HCC progression and CD133 expression in vivo.MTDH was positively correlated with immature dendritic,T helper 2 cells,central memory CD8^(+)T,memory B,activated dendritic,natural killer(NK)T,NK,activated CD4^(+)T,and central memory CD4^(+)T cells.MTDH was negatively correlated with activated CD8^(+)T cells,eosinophils,activated B cells,monocytes,macrophages,and mast cells.A positive correlation was observed between the MTDH level and CXCL2 expression,whereas a negative correlation was observed between the MTDH level and CX3CL1 and CXCL12 expression.CONCLUSION High levels of MTDH expression in patients with HCC are associated with poor prognosis,promoting tumor stemness,immune infiltration,and HCC progression.
基金supported by the National Natural Science Foundation of China(Nos.81872255,62141109)the Leading-Edge Technology Programme of Jiangsu Natural Science Foundation:BK20212021.
文摘Hepatocellular carcinoma(HCC)is a malignancy known for its unfavorable prognosis.The dysregulation of the tumor microenvironment(TME)can affect the sensitivity to immunotherapy or chemotherapy,leading to treatment failure.The elucidation of PHLDA2’s involvement in HCC is imperative,and the clinical value of PHLDA2 is also underestimated.Here,bioinformatics analysis was performed in multiple cohorts to explore the phenotype and mechanism through which PHLDA2 may affect the progression of HCC.Then,the expression and function of PHLDA2 were examined via the qRT-PCR,Western Blot,and MTT assays.Our findings indicate a substantial upregulation of PHLDA2 in HCC,correlated with a poorer prognosis.The methylation levels of PHLDA2 were found to be lower in HCC tissues compared to normal liver tissues.Besides,noteworthy associations were observed between PHLDA2 expression and immune infiltration in HCC.In addition,PHLDA2 upregulation is closely associated with stemness features and immunotherapy or chemotherapy resistance in HCC.In vitro experiments showed that sorafenib or cisplatin significantly up-regulated PHLDA2 mRNA levels,and PHLDA2 knockdown markedly decreased the sensitivity of HCC cells to chemotherapy drugs.Meanwhile,we found that TGF-βinduced the expression of PHLDA2 in vitro.The GSEA and in vitro experiment indicated that PHLDA2 may promote the HCC progression via activating the AKT signaling pathway.Our study revealed the novel role of PHLDA2 as an independent prognostic factor,which plays an essential role in TME remodeling and treatment resistance in HCC.
基金supported by the Doctoral Foundation of HuBei University of Science and Technology(Grant Numbers BK202007 and BK202028 to L.W.and Z.Z.)Special Research Fund Project of School of Stomatology and Optometry,Xianning Medical College,Hubei University of Science and Technology(Grant Number 2020XZ37 to L.W.)+3 种基金Hubei Provincial Department of Education“Hundred Schools and Hundred Counties”(Grant Number BXLBX0806 to Z.Z.)the Foundation of Hubei University of Science and Technology“Double Hundred Project”(Grant Number 2022HKSB01 to Z.Z.)the Foundation of Innovation Team of Hubei University of Science and Technology(Grant Number 2023T13 to S.Y.)Natural Science Foundation of Hubei Province(Grant Number 2023AFB1027 to Z.Z.).
文摘Background:IQGAP3 plays a crucial role in regulating cell proliferation,division,and cytoskeletal organization.Abnormal expression of IQGAP3 has been linked to various tumors,but its function in glioma is not well understood.Methods:Various methods,including genetic differential analysis,single-cell analysis,ROC curve analysis,Cox regression,Kaplan-Meier analysis,and enrichment analysis,were employed to analyze the expression patterns,diagnostic potential,prognostic implications,and biological processes involving IQGAP3 in normal and tumor tissues.The impact of IQGAP3 on immune infiltration and the immune microenvironment in gliomas was evaluated using immunofluorescence.Additionally,the cBioPortal database was used to analyze copy number variations and mutation sites of IQGAP3.Experimental validation was also performed to assess the effects of IQGAP3 on glioma cells and explore underlying mechanisms.Results:High IQGAP3 expression in gliomas is associated with an unfavorable prognosis,particularly in wild-type IDH and 1p/19q non-codeleted gliomas.Enrichment analysis revealed that IQGAP3 is involved in regulating the cell cycle,PI3K/AKT signaling,p53 signaling,and PLK1-related pathways.Furthermore,IQGAP3 expression may be closely related to the immunosuppressive microenvironment of glioblastoma.BRD-K88742110 and LY-303511 are potential drugs for targeting IQGAP3 in anti-glioma therapy.In vitro experiments showed that downregulation of IQGAP3 inhibits the proliferation and migration of glioma cells,with the PLK1/PI3K/AKT pathway potentially playing a crucial role in IQGAP3-mediated glioma progression.Conclusion:IQGAP3 shows promise as a valuable biomarker for diagnosis,prognosis,and immunotherapeutic strategies in gliomas.
基金supported by grants from the Natural Science Foundation of Hunan Province(2022JJ80044)the Youth Science Foundation of Xiangya Hospital(2019Q13).
文摘Finding biomarkers for immunotherapy is an urgent issue in cancer treatment.Cellular retinoic acid-binding protein 2(CRABP2)is a controversial factor in the occurrence and development of human tumors.However,there is limited research on the relationship between CRABP2 and immunotherapy response.This study found that negative correlations of CRABP2 and immune checkpoint markers(PD-1,PD-L1,and CTLA-4)were observed in breast invasive carcinoma(BRCA),skin cutaneous melanoma(SKCM),stomach adenocarcinoma(STAD)and testicular germ cell tumors(TGCT).In particular,in SKCM patients who were treated with PD-1 inhibitors,high levels of CRABP2 predicted poor prognosis.Additionally,CRABP2 expression was elevated in cancer-associated fibroblasts(CAFs)at the single-cell level.The expression of CRABP2 was positively correlated with markers of CAFs,such as MFAP5,PDPN,ITGA11,PDGFRα/βand THY1 in SKCM.To validate the tumor-promoting effect of CRABP2 in vivo,SKCM xenograft mice models with CRABP2 overexpression have been constructed.These models showed an increase in tumor weight and volume.Enrichment analysis indicated that CRABP2 may be involved in immunerelated pathways of SKCM,such as extracellular matrix(ECM)receptor interaction and epithelial-mesenchymal transition(EMT).The study suggests that CRABP2 may regulate immunotherapy in SKCM patients by influencing infiltration of CAFs.In conclusion,this study provides new insights into the role of CRABP2 in immunotherapy response.The findings suggest that CRABP2 may be a promising biomarker for PD-1 inhibitors in SKCM patients.Further research is needed to confirm these findings and to explore the clinical implications of CRABP2 in immunotherapy.
基金the National Natural Science Foundation of China(Grant Nos.82072816 and 81672553)the Natural Science Foundation of Shandong Province(Grant No.ZR2021LZY003).
文摘This research aims to identify the key fatty acid beta-oxidation(FAO)genes that are altered in kidney renal clear cell carcinoma(KIRC)and to analyze the role of these genes in KIRC The Gene Expression Omnibus(GEO)and FAO datasets were used to identify these key genes.Wilcoxon rank sum test was used to assess the levels of acyl-CoA dehydrogenase medium chain(ACADM)between KIRC and non cancer samples.The logistic regression and Wilcoxon rank sum test were used to explore the association between ACADM and clinical features.The diagnostic performance of ACADM for KIRC was asessed using a diagnostic receiver operating ch aracteristic(ROC)curve.The co-expressed genes of ACADM were identifed in LinkedOmics database,and their function and pathway enrichment were analyzed.The correlation between ACADM expression level and immune infitration was analyzed by Gene Set Variation Analysis(GSVA)method Additionally,the proliferation,migration,and invasion abilities of KIRC cells were assessed after overexpressing ACADM.Following differential analysis and intersection,we identifed six hub genes,induding ACADM.We found that the expression level of ACADM was decreased in KIRC tissues and had a better diagnostic efect(AUC=0.916).Survival analysis suggested that patients with decreased ACADM expression had a worse prognosis.According to correlation analysis,a variety of dinical features were associated with the expression level of ACADML By analyzing the infiltration level of immune cells,we found that ACADM may be related to the enrichment of immune cells.Finally,ACADM overexpression inhibited proliferation,migration,and invasion of KIRC cells.In conclusion,our findings suggest that reduced ACADM expression in KIRC patients is indicative of poor prognosis.These results imply that ACADM may be a diagnostic and prognostic marker for individuals with KIRC,offering a reference for dinicians in diagnosis and treatment.
基金Supported by National Natural Foundation of China,No.821742232019 Chinese and Western Medicine Clinical Collaborative Capacity Building Project for Major Difficult Diseases,No.2019-ZX-005。
文摘BACKGROUND Esophageal squamous cell carcinoma(ESCC)is one of the most common malignancies worldwide,and its development comprises a multistep process from intraepithelial neoplasia(IN)to carcinoma(CA).However,the critical regulators and underlying molecular mechanisms remain largely unknown.AIM To explore the genes and infiltrating immune cells in the microenvironment that are associated with the multistage progression of ESCC to facilitate diagnosis and early intervention.METHODS A mouse model mimicking the multistage development of ESCC was established by providing warter containing 4-nitroquinoline 1-oxide(4NQO)to C57BL/6 mice.Moreover,we established a control group without 4NQO treatment of mice.Then,transcriptome sequencing was performed for esophageal tissues from patients with different pathological statuses,including low-grade IN(LGIN),high-grade IN(HGIN),and CA,and controlled normal tissue(NOR)samples.Differentially expressed genes(DEGs)were identified in the LGIN,HGIN,and CA groups,and the biological functions of the DEGs were analyzed via Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses.The CIBERSORT algorithm was used to detect the pattern of immune cell infilt-ration.Immunohistochemistry(IHC)was also conducted to validate our results.Finally,the Luminex multiplex cytokine analysis was utilized to measure the serum cytokine levels in the mice.RESULTS Compared with those in the NOR group,a total of 681541,and 840 DEGs were obtained in the LGIN,HGIN,and CA groups,respectively.Using the intersection of the three sets of DEGs,we identified 86 genes as key genes involved in the development of ESCC.Enrichment analysis revealed that these genes were enriched mainly in the keratinization,epidermal cell differentiation,and interleukin(IL)-17 signaling pathways.CIBERSORT analysis revealed that,compared with those in the NOR group,M0 and M1 macrophages in the 4NQO group showed stronger infiltration,which was validated by IHC.Serum cytokine analysis revealed that,compared with those in the NOR group,IL-1βand IL-6 were upregulated,while IL-10 was downregulated in the LGIN,HGIN,and CA groups.Moreover,the expression of the representative key genes,such as S100a8 and Krt6b,was verified in external human samples,and the results of immunohistochemical staining were consistent with the findings in mice.CONCLUSION We identified a set of key genes represented by S100a8 and Krt6b and investigated their potential biological functions.In addition,we found that macrophage infiltration and abnormal alterations in the levels of inflam-mation-associated cytokines,such as IL-1β,IL-6,and IL-10,in the peripheral blood may be closely associated with the development of ESCC.
基金Supported by National Natural Science Foundation of China,No.82300347Natural Science Foundation of Ningbo,No.2021J296Science Foundation of Lihuili Hospital,No.2022ZD004.
文摘BACKGROUND Diabetic cardiomyopathy(DCM)is a multifaceted cardiovascular disorder in which immune dysregulation plays a pivotal role.The immunological molecular mechanisms underlying DCM are poorly understood.AIM To examine the immunological molecular mechanisms of DCM and construct diagnostic and prognostic models of DCM based on immune feature genes(IFGs).METHODS Weighted gene co-expression network analysis along with machine learning methods were employed to pinpoint IFGs within bulk RNA sequencing(RNA-seq)datasets.Single-sample gene set enrichment analysis(ssGSEA)facilitated the analysis of immune cell infiltration.Diagnostic and prognostic models for these IFGs were developed and assessed in a validation cohort.Gene expression in the DCM cell model was confirmed through real time-quantitative polymerase chain reaction and western blotting techniques.Additionally,single-cell RNA-seq data provided deeper insights into cellular profiles and interactions.RESULTS The overlap between 69 differentially expressed genes in the DCM-associated module and 2483 immune genes yielded 7 differentially expressed immune-related genes.Four IFGs showed good diagnostic and prognostic values in the validation cohort:Proenkephalin(Penk)and retinol binding protein 7(Rbp7),which were highly expressed,and glucagon receptor and inhibin subunit alpha,which were expressed at low levels in DCM patients(all area under the curves>0.9).SsGSEA revealed that IFG-related immune cell infiltration primarily involved type 2 T helper cells.High expression of Penk(P<0.0001)and Rbp7(P=0.001)was detected in cardiomyocytes and interstitial cells and further confirmed in a DCM cell model in vitro.Intercellular events and communication analysis revealed abnormal cellular phenotype transformation and signaling communication in DCM,especially between mesenchymal cells and macrophages.CONCLUSION The present study identified Penk and Rbp7 as potential DCM biomarkers,and aberrant mesenchymal-immune cell phenotype communication may be an important aspect of DCM pathogenesis.
基金supported by the Modern Traditional Chinese Medicine Haihe Laboratory science and technology project(22HHZYSS00005)and the National Administration of Traditional Chinese Medicine Young Qihuang Scholar Project.
文摘Background:This study aims to explore the involvement of ferroptosis-related genes and pathogenesis in pancreatic cancer and predict potential therapeutic interventions using Traditional Chinese Medicine(TCM).Methods:We utilized gene expression datasets,ferroptosis upregulated genes and applied machine learning algorithms,including LASSO and SVM-RFE,to identify key ferroptosis-related genes in pancreatic cancer.Perform Gene Ontology,Kyoto Encyclopedia of Genes and Genomes,and Disease Ontology enrichment analysis,immune infiltration analysis and correlation analysis between immune infiltrating cells and characteristic genes on differentially expressed genes using the R software package.Retrieve potential traditional Chinese medicine for targeted ferroptosis gene therapy for pancreatic cancer through Coremine and Herb databases.Results:Seventeen feature genes were identified,with significant implications for immune cell infiltration in pancreatic cancer.The results of immune cell infiltration analysis showed that B cells naive,B cells memory,T cells regulatory,and M0 macrophages were significantly upregulated in pancreatic cancer patients;Mast cells resting were significantly downregulated.Chinese herbal medicines such as ginkgo,turmeric,ginseng,Codonopsis pilosula,Zedoary turmeric,deer tendons,senna leaves,Guanmu Tong,Huangqi,and Banzhilian are potential drugs for targeted ferroptosis gene therapy for pancreatic cancer.Conclusion:TIMP1 emerged as a key gene,with several TCM herbs predicted to modulate its expression,offering new avenues for treatment.
文摘Background: A major cause of cancer death worldwide is bladder cancer, which is the most common malignant tumor of the urinary tract. PAEP is a member of the kernel lipocalin superfamily whose members share relatively low sequence similarity but have highly conserved exon/intron structure and three-dimensional protein folding. Most lipocalins are clustered on the long arm of chromosome 9. The purpose of this study was to clarify the correlation between PAEP expression level and bladder cancer. Methods: In the TCGA database, we obtained clinical and RNA sequencing data of 431 BLCA patients, including 412 BLCA tissues and 19 normal bladder tissues in the study. Analyses of bioinformatics were conducted in this study to determine the role of PAEP in bladder cancer. A quantitative real-time PCR method was used to quantitate the gene expression profile. Additionally, the effect of PAEP on tumor immune infiltration and prognosis was analyzed. Results: PAEP was a poor prognostic biomarker of bladder cancer because it was significantly upregulated. bladder cancer patients with higher PAEP expression had poor outcomes. An AUC of 0.780 was calculated from the area under the ROC curve. PAEP was associated with T stage, pathologic stage, Histologic grade and Subtype of bladder cancer patients, and served as an independent predictor of overall survival in bladder cancer patients. Functional enrichment analysis revealed PAEP was obviously enriched in pathways connected with carcinogenesis and immunosuppression. The expression of PAEP was significantly associated with tumor immune cells and immune checkpoints according to ssGSEA and Spearman correlation analysis. Conclusions: In this study, we screened and detected a mRNA, PAEP is a prognostic and immune-related biomarker in BLCA, which may contribute to the early diagnosis and treatment of BLCA.
基金supported by the National Natural Science Foundation of China[No.81602020]the Tianjin Medical University Cancer Institute&Hospital Research Project[No.1805].
文摘Background:The molecular mechanism underlying the involvement of the Transferrin receptor(TFRC)in cervical cancer remains poorly understood.This study aims to elucidate the role of TFRC in cervical cancer by analyzing data from The Cancer Genome Atlas(TCGA)and Genotype-Tissue Expression(GTEx)databases.Methods:TFRC protein expression was obtained from Human Protein Altas(HPA).All datas were collected from TCGA and GTEx.In this study,we analyzed the expression of TFRC in cervical cancer and its clinical significance.Through Kyoto Encyclopedia of Genes and Genomes(KEGG)and Gene set enrichment analyses(GSEA),investigated the related molecular pathways of TFRC.The relationship between TFRC and immune infiltration was then examined.The prognosis of different immune cell subsets was then analyzed after dividing cervical cancer patients into high and low expression of TFRC groups.Results:TFRC is highly expressed in various tumor tissues compared to control normal tissues,including cervical cancer.An increased expression of TFRC was associated with higher Tumor(T)and Node(N)stage,as well as a higher clinical stage.Kaplan–Meier(KM)survival analysis investigated that higher TFRC expression patients have a poor overall survival(OS),disease specific survival(DSS)and progress free interval(PFI).Both KEGG and GSEA enriched signaling pathway by high TFRC and low TFRC groups.There was a significant negative linear correlation between TFRC expression and immune infiltration.TFRC affects the prognosis of cervical cancer patients through immune pathway.Conclusions:Cervical cancer patients with TFRC expression may have a worse prognosis.
基金This work was supported by a project funded by the National Natural Science Foundation of China (82260110,81870449,82170674,51933011)China Postdoctoral Science Foundation (2019M653904XB)Natural Science Foundation of Xinjiang Uyghur Autonomous Region (2020D01C006).
文摘Background:Hepatocellular carcinoma(HCC)is a leading cause of cancer-related death worldwide.The development of biomarkers for early detection and monitoring of HCC has not shown significant prog-ress.Meanwhile,the second adenomatous polyposis-related gene,MUTYH,which encodes a DNA gly-cosylase,has been observed in its contribution to oxidative DNA damage repair.Abnormal expression of MUTYH can reduce cell survival rate.Therefore,this study investigated the usefulness of MUTYH in diagnosing and prognosis HCC.Materials and methods:Using The Cancer Genome Atlas(TCGA)data,we analyzed the prognostic value of MUTYH in HCC.We used logistic regression,Wilcoxon signed-rank test,and KruskaleWallis test to examine MUTYH expression concerning clinical-pathologic characteristics.Univariate and multivariate Cox regression methods and Kaplan-Meier analysis were applied to determine the related prognostic factors of HCC.The enrichment analysis(GSEA)was used to determine the critical pathways associated with MUTYH.The single-sample gene set enrichment analysis(ssGSEA)was conducted to examine the correlation between MUTYH expression and cancer immune infiltration.Results:The higher expression of MUTYH in HCC patients was associated with a poorer overall survival rate and a shorter disease-specific survival rate.The Kyoto Encyclopedia of Genes and Genomes(KEGG)analysis showed that all differentially expressed genes(DEGs)between the high and low expression levels of MUTYH significantly enriched in the trace ligand-receptor interaction,cell cycle,oocyte meiosis,gap junction,and DNA replication.Group analysis revealed the signals of their open access.The neuron system,M phase,DNA repair,Rho GTPase effector,and cell cycle checkpoints were significantly enriched.ssGSEA showed a positive correlation between MUTYH expression and the infiltration levels of Th2 cells,NK cells,and T helper cells.Moreover,a negative correlation was found between MUTYH expression and the infiltration levels of dendritic cells(DCs)and cytotoxic cells.Conclusions:MUTYH expression levels were positively correlated with immune checkpoint gene expression levels in HCC tissues.The expression level of MUTYH was related to the prognosis of HCC and the immune infiltration of HCC.
基金This work is supported by the National Natural Science Foundation of China(No.81703072)The Natural Science Foundation of Zhejiang Province(No.LQ21H160027)。
文摘Objective:Most patients with advanced lung cancer have a poor prognosis.Recent studies have identified TRIM59 as a novel molecule that serves as a prognostic factor for the progression of non-small cell lung cancer.In the present study,we investigated the role of TRIM59 in predicting the prognosis of lung adenocarcinoma(LUAD)as well as the correlation between TRIM59 expression and immune infiltrates.Methods:We analyzed TRIM59 expression in normal and tumor tissues based on RNA-sequencing datasets from The Cancer Genome Atlas and Genotype-Tissue Expression databases.Forty-seven cases of LUAD tissues and their matching adjacent tissues were collected,and TRIM59 expression in tissue samples was demonstrated by immunohistochemistry.All tissue specimens were obtained under the approval of the Medical Ethics Committee of the Second Affiliated Hospital of Zhejiang University School of Medicine(approval No.IR2019001101;approved on April 3,2019).The immune cell scores were calculated using the CIBERSORT database.The Tumor Immune Estimation Resource database was used to analyze the correlation between TRIM59 and immune cell activities.Results:TRIM59 was up-regulated in most cancer types.High TRIM59 expression predicted a worse prognosis in patients with LUAD(overall survival,P=0.00096;disease-specific survival,P=0.00056;disease-free interval,P=0.0009;progression-free interval,P=0.0012).Moreover,TRIM59 was highly expressed in patients with LUAD who had a poorer prognosis.TRIM59 also showed a significant correlation with the ESTIMATE score(P=0.04)and stromal score(P=0.005)in patients with LUAD.Notably,a significant correlation between TRIM59 and the tumor mutation burden was found in LUAD but in no other cancer types(P<0.001).Further investigation showed that TRIM59 had a significant correlation with gene markers on neutrophils and dendritic cells.Conclusion:TRIM59 is a potential prognosticator in LUAD and may be correlated with immune cell identification,immune cell infiltration,and immunotherapy checkpoints in LUAD.
基金supported by grants from the National Natural Science Foundation of China(Grant No.82060483)Guangxi Research Foundation for Science&Technology Base and Talent Special(Grant No.AD19110079)Natural Science Foundation of Guangxi Province(Grant No.2020GXNSFBA238002).
文摘Background:Cytochrome b561(CYB561)plays a critical role in neuroendocrine function,cardiovascular regulation,and tumor growth;however,the prognostic value of CYB561 in patients with breast cancer and the relationship between CYB561 expression and immune infiltration in breast cancer remain unclear.Methods:The mRNA expression and clinical data of patients with breast cancer were obtained from The Cancer Genome Atlas database.Functional enrichment analysis was used to explore underlying biological functions associated with CYB561.The methylation status of CYB561 was analyzed using the MethSurv database.The enrichment score of immune cell infiltration for CYB561 in breast cancer was calculated using single-sample gene set enrichment analysis.The prognostic value of CYB561 was evaluated using Kaplan-Meier method and Cox regression analysis.Based on the results of the multivariate Cox analysis,a nomogram was constructed to predict the effect of CYB561 expression on overall survival(OS).Results:The results showed that CYB561 was highly expressed in breast cancer tissues.Hypomethylation of CYB561 is associated with an unfavorable prognosis.In multivariate Cox regression analysis,CYB561 was an independent prognostic factor for OS.Functional enrichment analysis indicated that estrogen signaling pathway,inflammatory response,KRAS signaling pathway,epithelial-mesenchymal transition,leukocyte migration,and regulation of lymphocyte activation were strongly enriched in the low CYB561 expression group.Additionally,CYB561 expression was negatively correlated with immune infiltration of B cells,plasmacytoid dendritic cells,dendritic cells,and neutrophils.Conclusion:CYB561 may serve as a potential biomarker for breast cancer diagnosis and prognosis.
基金the National Natural Science Foundation of China,No.82273457 and No.81501539Guangdong Basic and Applied Basic Research Foundation,No.2023A1515012762 and No.2021A1515012180+1 种基金Special Grant for Key Area Programs of Guangdong Department of Education,No.2021ZDZX2040Science and Technology Special Project of Guangdong Province,No.210715216902829.
文摘BACKGROUND Immune cells play an important role in regulating the behavior of tumor cells.According to emerging evidence,six-transmembrane epithelial antigen of the prostate 4(STEAP4)performs a crucial part in tumor microenvironmental immune response and tumorigenesis,and serves as the potential target for cellular and antibody immunotherapy.However,the immunotherapeutic role of STEAP4 in gastric cancer(GC)remains unclear.AIM To investigate the expression of STEAP4 in GC and its relationship with immune infiltrating cells,and explore the potential value of STEAP4 as an immune prognostic indicator in GC.METHODS The expression level of STEAP4 was characterized by immunohistochemistry in tumors and adjacent non-cancerous samples in 96 GC patients.Tumor Immune Estimation Resource was used to study the correlation between STEAP4 and tumor immune infiltration level and immune infiltration gene signature.R package was used to analyze the relationship between STEAP4 expression and immune and stromal scores in GC(GSE62254)by the ESTIMATE algorithm,and Kaplan-Meier Plotter and Gene Expression Profiling Interactive Analysis were applied to analyze the effect of STEAP4 on clinical prognosis.RESULTS Immunohistochemistry analysis showed that STEAP4 expression was higher in GC tissues than in adjacent tissues,and STEAP4 expression was positively correlated with the clinical stage of GC.In GC,the expression of STEAP4 was positively correlated with the infiltration levels of B cells,CD4+T cells,macrophages,neutrophils,and dendritic cells.The expression level of STEAP4 was strongly correlated with most of the immune markers.In addition,STEAP4 expression was inversely correlated with tumor purity,but correlated with stromal score(r=0.43,P<0.001),immune score(r=0.29,P<0.001)and estimate score(r=0.39,P<0.001).Moreover,stromal,immune,and estimate scores were higher in the STEAP4 high expression group,whereas tumor purity was higher in the STEAP4 Low expression group.The relationship between STEAP4 expression and prognosis of patients with GC was further investigated,and the results showed that high STEAP4 expression was associated with poor overall survival and disease-free survival.In addition,Kaplan-Meier Plotter showed that high expression of STEAP4 was significantly correlated with poor survival of patients with GC.CONCLUSION The current findings suggest an oncogenic role for STEAP4 in GC,with significantly high levels being associated with poor prognosis.Investigation of the GC tumor microenvironment suggests the potential function of STEAP4 is connected with the infiltration of diverse immune cells,which may contribute to the regulation of the tumor microenvironment.In conclusion,STEAP4 may serve as a potential therapeutic target for GC to improve the immune infiltration,as well as serve as a prognostic biomarker for judging the prognosis and immune infiltration status of GC.
文摘BACKGROUND Intrahepatic cholangiocarcinoma(ICC)is a malignant tumor of the hepatobiliary system with concealed onset,strong invasiveness and poor prognosis.AIM To explore the disease characteristic genes that may be helpful in the diagnosis of ICC and affect immune cell infiltration.METHODS We downloaded two ICC-related human gene expression profiles from GEO database as the training group(GSE26566 and GSE32958 datasets)for difference analysis,and performed enrichment analysis on differential genes.The least absolute shrinkage and selection operator(LASSO),support vector machinerecursive feature elimination(SVM-RFE)and random forest(RF),three machine learning algorithms,were used to screen the characteristic genes.Double verification was carried out on GSE107943 and The Cancer Genome Atlas,two verification groups.Receiver operating characteristic curve and area under the curve(AUC)were used to evaluate the diagnostic efficacy of genes for ICC.CIBERSORT and ssGSEA algorithms were used to evaluate the effect of characteristic genes on immune infiltration pattern.Human Protein Atlas(HPA)was used to analyze the protein expression level of the target gene.RESULTS A total of 1091 differential genes were obtained in the training group.Enrichment analysis showed that the above genes were mainly enriched in small molecular catabolism,complement and coagulation cascade,bile secretion and other functions and pathways.Twentyfive characteristic genes were screened by LASSO regression,19 by SVM-RFE algorithm,and 30 by RF algorithm.Three algorithms were used in combination to determine the characteristic gene of ICC:MMP14.The verification group confirmed that the genes had a high diagnostic accuracy(AUC values of the training group and the verification group were 0.960,0.999,and 0.977,respectively).Comprehensive analysis of immune infiltration showed that MMP14 could affect the infiltration of monocytes,activated memory CD4 T cells,resting memory CD4 T cells,and other immune cells,and was closely related to the expression of CD200,cytotoxic T-lymphocyteassociated antigen 4,CD14,CD44,and other immune checkpoints.The results of immunohistochemistry in HPA database showed was indeed overexpressed in ICC.CONCLUSION MMP14 can be used as a disease characteristic gene of ICC,and may regulate the distribution of immune-infiltrating cells in the ICC tumor microenvironment,which provides a new method for the determination of ICC diagnostic markers and screening of therapeutic targets.
