Objective:To investigate the effects of Eriocitrin on the proliferation and migration of Lung adenocarcinoma(LUAD)cells A549 and H1299,and the mechanism of Epithelial-Mesenchymal Transition(EMT).Methods:The effects of...Objective:To investigate the effects of Eriocitrin on the proliferation and migration of Lung adenocarcinoma(LUAD)cells A549 and H1299,and the mechanism of Epithelial-Mesenchymal Transition(EMT).Methods:The effects of different Eriocitrin on the proliferation of LUAD cells A549 and H1299 were examined by CCK8 method.EMT-associated epithelial calmodulin(E-cadherin and N-cadherin),vimentin,ferroptosis-associated protein SLC7A11,GPX4,FTH were detected by Western Blot and expression of mRNA of EMT marker molecules E-cadherin,N-cadherin,Snail were detected by qRT-PCR.Effects of saccharomyces cerevisiae suberin on ferroptosis in LUAD cells as observed by lipid reactive oxygen species(ROS)assay.Results:Eriocitrin could significantly inhibit the proliferative behavior of LUAD cells A549 and H1299 and showed a certain dose-and time-dependence.Compared with the control group,different concentrations of Eriocitrin could significantly reduce the scratch healing rate after 24 and 48 h of action,and the difference was statistically significant(P<0.01).The expression of ROS is increased,EMT-related protein E-cadherin was increased in LUAD cells A549 and H1299 compared with the control group after the intervention with Eriocitrin.N-cadherin and Vimentin expression was decreased.E-cadherin mRNA expression was increased,and N-cadherin,Snail mRNA expression was decreased,expression of ferroptosis-associated protein SLC7A11,GPX4,FTH was decreased,the difference was statistically significant(P<0.05).Conclusion:Eriocitrin may inhibit the proliferation and migration of LUAD cells by regulating the EMT pathway and has potential application in LUAD prevention and adjuvant chemotherapy.展开更多
Objective: Radiotherapy has been widely used to treat lung cancer. However, non-small lung cancer cells are insensitive to radiation, diminishing their radiotherapy effects. Although the radiosensitivity of the non-sm...Objective: Radiotherapy has been widely used to treat lung cancer. However, non-small lung cancer cells are insensitive to radiation, diminishing their radiotherapy effects. Although the radiosensitivity of the non-small lung cancer cells was reported to be enhanced through regulating miR-34a, the regulation effects of miR-34a expression on radiosensitivity of lung adenocarcinoma cells through target genes CDK4, CDK6, CyclinD1, and Bcl-2/Bax have not been systematically investigated. Methods: In this study, we investigated the effect of miR-34a expression on the Bcl-2, CDK4, and CDK6 pathways in lung adenocarcinoma cells, to provide new insights into the sensitization treatment of lung cancer. We first studied the effect of miR-34a expression on H1299 and A549 cell activity. Then to investigate the mechanisms of radiosensitivity, we focused on apoptosis, cell cycle, and target genes. Results: We find that overexpression of miR-34a in lung adenocarcinoma cells inhibits cell activity, and improves radiosensitivity. Specifically, overexpression of miR-34a suppresses the expression of target genes CDK4, CDK6, CyclinD1, and Bcl-2/Bax, which leads to cell cycle arrest and promotes apoptosis of lung adenocarcinoma cells. Conclusions: Overall, our results demonstrate that the overexpression of miR-34a enhances the radiosensitivity of lung adenocarcinoma cells, indicating that miR-34a is a sensitizer for lung adenocarcinoma radiotherapy.展开更多
Objective: To test the coalescence effect of two chemotherapy drugs at low effective dose(cisplatin and taxotere) combined with pomegranate juice on A549 cancer cells. Methods: Infrared spectroscopy method is a qualit...Objective: To test the coalescence effect of two chemotherapy drugs at low effective dose(cisplatin and taxotere) combined with pomegranate juice on A549 cancer cells. Methods: Infrared spectroscopy method is a qualitative test that was performed to ensure the existence of the phytochemicals providing the antioxidant activity through the presence of the hydroxyl group(-OH). The viability of A549 cell line and normal MCs was tested using the neutral red uptake, Clonogenic survival, XTT and Cell migration assays. Results: Our results showed that this combination firstly led to a greater decrease in the viability of cells comparing to those treated with chemotherapy drugs alone, and secondly led to a significant reduction in cell migration. Conclusions: These data suggest a synergistic effect between the pomegranate and cisplatin which makes probably this combination a powerful option for treating lung adenocarcinoma and in parallel minimizing the systemic side effects.展开更多
Objective: Her-2/neu protein overexpression has been demonstrated in Non-small cell lung cancer, especially in lung adenocarcinoma. Its overexpression often indicates a poor prognosis. Therapeutic agents against her-2...Objective: Her-2/neu protein overexpression has been demonstrated in Non-small cell lung cancer, especially in lung adenocarcinoma. Its overexpression often indicates a poor prognosis. Therapeutic agents against her-2/neu have been intensively sought over the past decades. The objective of this paper is to investigate the effect of chemically synthesized siRNA targeting her-2/neu on her-2/neu dysregulated human lung adenocarcinoma cells. Methods: Calu-3 cells were transfected with siRNAs formulated LipofectAMINE 2000. The her-2/neu mRNA and protein levels were detected by RT-PCR and flow cytometry (FCM). The biological morphology and growth inhibition of calu-3 cells were observed with light microscopy and MTT assay, respectively. The cell cycle and apoptosis rate were analyzed by FCM. Results: siRNA targeting Her-2/neu down-regulated the transcription of her-2/neu oncogene and protein level. Slowed cell proliferation and cell cycle arrest at G0/1 stage could be also observed, accompanied with enhanced cell apoptosis. Conclusion: Specific siRNA targeting her-2/neu can effectively inhibit her-2/neu expression in her-2/neu overexpressing calu-3 cell lines. siRNA-mediated gene silencing may be a useful therapeutic strategy for cancer.展开更多
Using FX-4000 strain unit, the prolieration in human lung adenocarcinoma A549 cells that underwent mechanical strain of different waveform、frequency and duration were studied. Image analysis revealed that cellular pr...Using FX-4000 strain unit, the prolieration in human lung adenocarcinoma A549 cells that underwent mechanical strain of different waveform、frequency and duration were studied. Image analysis revealed that cellular proliferation rate(PR) reduced significantly after cells were subjected to square wave with 0～20% elongation at frequency 30,40,50 and 60 cycles/min for 2h. The PR had no distinct difference at heart wave , triangle wave and sine wave group compared with control. It is concluded that square wave and higher frequency play an important role in inhibiting A549 cells proliferation.展开更多
The use of anti-beta 1 integrin monoclonal antibody in lung cancer treatment has proven beneficial.Here,we developed a novel monoclonal antibody(mAb),called P5,by immunizing mice with human peripheral blood mononuclea...The use of anti-beta 1 integrin monoclonal antibody in lung cancer treatment has proven beneficial.Here,we developed a novel monoclonal antibody(mAb),called P5,by immunizing mice with human peripheral blood mononuclear cells(PBMC).Its anti-tumor effect is now being tested,in a clinical phase HI trial,in combinatorial treatments with various chemical drugs.To confirm that P5 indeed binds to beta 1 integrin,cell lysates were immunoprecipitated with commercial anti-beta 1 integrin mAb(TS2/16) and immunoblotted against P5 to reveal a140 kDa molecular weight band,as expected.Immunoprecipitation with P5 followed by LC/MS protein sequence analysis further verified P5 antigen to be beta 1 integrin.Cisplatin treatment upregulated cell surface expression of beta 1 integrin in A549 cells,while causing inhibition of cell growth.When cells were co-treated with different concentrations of P5 mAb,the cisplatin-mediated inhibitory effect was enhanced in a dose-dependent manner.Our findings show that a combinatorial treatment of P5 mAb and cisplatin in A549 cells resulted in a 30%increase in apoptosis,compared to baseline,and significantly more when compared to either the cisplatin or P5 alone group.The entire peptide sequences in CDR from variable region of Ig heavy and light chain gene for P5 mAb are also disclosed.Together,these results provide evidence of the beneficial effect of P5 mAb in combinatorial treatment of human lung adenocarcinoma.展开更多
Background:Cytotoxic T lymphocytes(CD8+T)cells function critically in mediating anti-tumor immune response in cancer patients.Characterizing the specific functions of CD8+T cells in lung adenocarcinoma(LUAD)could help ...Background:Cytotoxic T lymphocytes(CD8+T)cells function critically in mediating anti-tumor immune response in cancer patients.Characterizing the specific functions of CD8+T cells in lung adenocarcinoma(LUAD)could help better understand local anti-tumor immune responses and estimate the effect of immunotherapy.Methods:Gens related to CD8+T cells were identified by cluster analysis based on the single-cell sequencing data of three LUAD tissues and their paired normal tissues.Weighted gene co-expression network analysis(WGCNA),consensus clustering,differential expression analysis,least absolute shrinkage and selection operator(LASSO)and Cox regression analysis were conducted to classify molecular subtypes for LUAD and to develop a risk model using prognostic genes related to CD8+T cells.Expression of the genes in the prognostic model,their effects on tumor cell invasion,and interactions with CD8+T cells were verified by cell experiments.Results:This study defined two LUAD clusters(CD8+0 and CD8+1)based on CD8+T cells,with cluster CD8+0 being significantly associated with the prognosis of LUAD.Three heterogeneous subtypes(clusters 1,2,and 3)differing in prognosis,genome mutation events,and immune status were categorized using 42 prognostic genes.A prognostic model created based on 11 significant genes(including CD200R1,CLEC17A,ZC3H12D,GNG7,SNX30,CDCP1,NEIL3,IGF2BP1,RHOV,ABCC2,and KRT81)was able to independently estimate the death risk for patients in different LUAD cohorts.Moreover,the model also showed general applicability in external validation cohorts.Low-risk patients could benefit more from taking immunotherapy and were significantly related to the resistance to anticancer drugs.The results from cell experiments demonstrated that the expression of CD200R1,CLEC17A,ZC3H12D,GNG7,and SNX30 was significantly downregulated,while that of CDCP1,NEIL3,IGF2BP1,RHOV,ABCC2 and KRT81 was upregulated in LUAD cells.Inhibition of CD200R1 greatly increased the invasiveness of the LUAD cells,but inhibiting CDCP1 expression weakened the invasion ability of LUAD cells.Conclusion:This study defined two prognostic CD8+T cell clusters and classified three heterogeneous molecular subtypes for LUAD.A prognostic model predictive of the potential effects of immunotherapy on LUAD patients was developed.展开更多
Lung cancer is the leading cause of cancer-related deaths globally.In recent years,with the widespread use of genetic testing,epidermal growth factor receptor–tyrosine kinase inhibitor(EGFR-TKI)–targeted drugs have ...Lung cancer is the leading cause of cancer-related deaths globally.In recent years,with the widespread use of genetic testing,epidermal growth factor receptor–tyrosine kinase inhibitor(EGFR-TKI)–targeted drugs have been efficacious to patients with lung adenocarcinoma exhibiting EGFR mutations.However,resistance to treatment is inevitable and eventually leads to tumor progression,recurrence,and reduction in the overall treatment efficacy.Lung cancer stem cells play a crucial role in the development of resistance toward EGFR-TKI–targeted therapy for lung adenocarcinoma.Lung cancer stem cells possess self-renewal,multilineage differentiation,and unlimited proliferation capabilities,which efficiently contribute to tumor formation and ultimately lead to tumor recurrence andmetastasis.In this study,we evaluated the origin,markers,stemness index,relevant classic studies,resistance mechanisms,related signaling pathways,and strategies for reversing lung cancer stem cell resistance to EGFR-TKIs to provide new insights on delaying or reducing resistance and to improve the treatment efficacy of patients with EGFR-mutated lung adenocarcinoma in the future.展开更多
Advanced LUAD shows limited response to treatment including immune therapy.With the development of sequencing omics,it is urgent to combine high-throughput multi-omics data to identify new immune checkpoint therapeuti...Advanced LUAD shows limited response to treatment including immune therapy.With the development of sequencing omics,it is urgent to combine high-throughput multi-omics data to identify new immune checkpoint therapeutic response markers.Using GSE72094(n=386)and GSE31210(n=226)gene expression profile data in the GEO database,we identified genes associated with lung adenocarcinoma(LUAD)death using tools such as“edgeR”and“maftools”and visualized the characteristics of these genes using the“circlize”R package.We constructed a prognostic model based on death-related genes and optimized the model using LASSO-Cox regression methods.By calculating the cell death index(CDI)of each individual,we divided LUAD patients into high and low CDI groups and examined the relationship between CDI and overall survival time by principal component analysis(PCA)and Kaplan-Meier analysis.We also used the“ConsensusClusterPlus”tool for unsupervised clustering of LUAD subtypes based on model genes.In addition,we collected data on the expression of immunomodulatory genes and model genes for each cohort and performed tumor microenvironment analyses.We also used the TIDE algorithm to predict immunotherapy responses in the CDI cohort.Finally,we studied the effect of PRKCD on the proliferation and migration of LUAD cells through cell culture experiments.The study utilized the TCGA-LUAD cohort(n=493)and identified 2,901 genes that are differentially expressed in patients with LUAD.Through KEGG and GO enrichment analysis,these genes were found to be involved in a wide range of biological pathways.The study also used univariate Cox regression models and LASSO regression analyses to identify 17 candidate genes that were best associated with mortality prognostic risk scores.By comparing the overall survival(OS)outcomes of patients with different CDI values,it was found that increased CDI levels were significantly associated with lower OS rates.In addition,the study used unsupervised cluster analysis to divide 115 LUAD patients into two distinct clusters with significant differences in OS timing.Finally,a prognostic indicator called CDI was established and its feasibility as an independent prognostic indicator was evaluated by Cox proportional risk regression analysis.The immunotherapy efficacy was more sensitive in the group with high expression of programmed cell death models.Relationship between programmed cell death(PCD)signature models and drug reactivity.After evaluating the median inhibitory concentration(IC50)of various drugs in LUAD samples,statistically significant differences in IC50 values were found in cohorts with high and low CDI status.Specifically,Gefitinib and Lapatinib had higher IC50 values in the high-CDI cohort,while Olaparib,Oxaliplatin,SB216763,and Axitinib had lower values.These results suggest that individuals with high CDI levels are sensitive to tyrosine kinase inhibitors and may be resistant to conventional chemotherapy.Therefore,this study constructed a gene model that can evaluate patient immunotherapy by using programmed cell death-related genes based on muti-omics.The CDI index composed of these programmed cell death-related genes reveals the heterogeneity of lung adenocarcinoma tumors and serves as a prognostic indicator for patients.展开更多
The platinum-based chemotherapy is one of the most frequently used treatment protocols for lung adenocarcinoma(LUAD),and chemoresistance,however,usually results in treatment failure and limits its application in the c...The platinum-based chemotherapy is one of the most frequently used treatment protocols for lung adenocarcinoma(LUAD),and chemoresistance,however,usually results in treatment failure and limits its application in the clinic.It has been shown that microRNAs(miRNAs)play a significant role in tumor chemoresistance.In this study,miR-125b was identified as a specific cisplatin(DDP)-resistant gene in LUAD,as indicated by the bioinformatics analysis and the real-time quantitative PCR assay.The decreased serum level of miR-125b in LUAD patients was correlated with the poor treatment response rate and short survival time.MiR-125b decreased the A549/DDP proliferation,and the multiple drug resistance-and autophagy-related protein expression levels,which were all reversed by the inhibition of miR-125b.In addition,xenografts of human tumors in nude mice were suppressed by miR-125b,demonstrating that through autophagy regulation,miR-125b could reverse the DDP resistance in LUAD cells,both in vitro and in vivo.Further mechanistic studies indicated that miR-125b directly repressed the expression levels of RORA and its downstream BNIP3L,which in turn inhibited autophagy and reversed chemoresistance.Based on these findings,miR-125b in combination with DDP might be an effective treatment option to overcome DDP resistance in LUAD.展开更多
Dear Editor,Lung adenocarcinoma with choroidal metastasis is a common form of cancer,with breast cancer accounting for 40%-53%and lung cancer accounting for 20%-29%of primary cases with choroidal metastases[1].This ty...Dear Editor,Lung adenocarcinoma with choroidal metastasis is a common form of cancer,with breast cancer accounting for 40%-53%and lung cancer accounting for 20%-29%of primary cases with choroidal metastases[1].This type of metastatic cancer typically affects people aged 40-70y,and is more prevalent in women than men[1].Ocular symptoms,including vision loss,can be an early indication of the disease,as many tumors are asymptomatic in their early stages.Studies have shown that 40.3%of cases involve the macular region,which explains why ocular symptoms are often the first manifestation of the disease[2].When choroidal metastasis is suspected in patients without a history of cancer,a combination of diagnostic tools should be used to identify the primary source of the tumor.Choroidal tumors can serve as an indication of future lung cancer diagnosis in some patients with lung cancer[1].In this report,we present a case of bilateral lung adenocarcinoma where ocular symptoms were the first indication of the disease.展开更多
Background:The aberrant intraellular expression of a mitochondrial aspartyl tRNA synthetase 2(DARS2)has been reported in human cancers.Nevertheless its critical role and detailed mechanism in lung adenocarcinoma(LUAD)...Background:The aberrant intraellular expression of a mitochondrial aspartyl tRNA synthetase 2(DARS2)has been reported in human cancers.Nevertheless its critical role and detailed mechanism in lung adenocarcinoma(LUAD)remain unexplored.Methods:Initially,The Cancer Genome Atlas(TCGA)based Gene Expression Profiling Interactive Analysis(GEPIA)database (http:/gepia.cancer-pku.cn/)was used to analyze the prognostic relevance of DARS2 expression in LUAD.Further,cell counting kit(CCK)8,immunostaining,and transwell invasion assays in LUAD cell lines in vitro,as well as DARS2 silence on LUAD by tumorigenicity experiments in wivo in nude mice,were performed.Besides,we analyzed the expression levels of p-PI3K(phosphorylated Phosphotylinosital3 kinase),PI3K,AKT(Protein Kinase B),p-AKT(phosphorylated Protein Kinase B),PCNA(proliferating cell nudear antigen),cleaved-caspase 3,E cadherin,and N-cadherin proteins using the Westem blot analysis.Results:LUAD tissues showed higher DARS2 expression compared to normal tissues.Upregulation of DARS2 could be related to Tumor-Node-Metastasis(TNM)stage,high lymph node metastasis,and inferior prognosis.DARS2 silence decreased the proliferation,migration,and invasion abilities of LUAD cells.In addition,the DARS2 downregulation decreased the PCNA and N-cadherin expression and increased cleaved:caspase 3 and E cadherin expressions in LUAD cells,coupled with the inactivation of the PI3K/AKT signaling pathway.Moreover,DARS2 silence impaired the tumonigenicity of LUAD in vivo.Interestingly,let:7b-5p could recognize DARS2 through a complementary sequence.Mechanistically,the increased let 7b 5p expression attenuated the promo oncogenic action of DARS2 during LUAD progression,which were inversely correlated to each other in the LUAD tssues Conclusion:In summary,let 7b-5p,downregulated DARS2 expression,regulating the progression of LUAD cells by the PI3K/AKT signaling pathway.展开更多
BACKGROUND Heat shock protein A4(HSPA4)belongs to molecular chaperone protein family which plays important roles within variable cellular activities,including cancer initiation and progression.However,the prognostic a...BACKGROUND Heat shock protein A4(HSPA4)belongs to molecular chaperone protein family which plays important roles within variable cellular activities,including cancer initiation and progression.However,the prognostic and immunological significance of HSPA4 in lung adenocarcinoma(LUAD)has not been revealed yet.AIM To explore the prognostic and immunological roles of HSPA4 to identify a novel prognostic biomarker and therapeutic target for LUAD.METHODS We assessed the prognostic and immunological significance of HSPA4 in LUAD using data from The Cancer Genome Atlas database.The association between HSPA4 expression and clinical-pathological features was assessed through Kruskal-Wallis and Wilcoxon signed-rank test.Univariate/multivariate Cox regression analyses and Kaplan-Meier curves were employed to evaluate prognostic factors,including HSPA4,in LUAD.Gene set enrichment analysis(GSEA)was conducted to identify the key signaling pathways associated with HSPA4.The correlation between HSPA4 expression and cancer immune infiltration was evaluated using single-sample gene set enrichment analysis(ssGSEA).RESULTS Overexpressing HSPA4 was significantly related to advanced pathologic TNM stage,advanced pathologic stage,progression disease status of primary therapy outcome and female subgroups with LUAD.In addition,increased HSPA4 expression was found to be related to worse disease-specific survival and overall survival.GSEA analysis indicated a significant correlation between HSPA4 and cell cycle regulation and immune response,particularly through diminishing the function of cytotoxicity cells and CD8 T cells.The ssGSEA algorithm showed a positive correlation between HSPA4 expression and infiltrating levels of Th2 cells,while a negative correlation was observed with cytotoxic cell infiltration levels.CONCLUSION Our findings indicate HSPA4 is related to prognosis and immune cell infiltrates and may act as a novel prognostic biomarker and therapeutic target for LUAD.展开更多
Interferon-gamma(IFN-γ)plays a dual role in cancer;it is both a pro-and an antitumorigenic cytokine,depending on the type of cancer.The deregulation of the IFN-γcanonic pathway is associated with several disorders,i...Interferon-gamma(IFN-γ)plays a dual role in cancer;it is both a pro-and an antitumorigenic cytokine,depending on the type of cancer.The deregulation of the IFN-γcanonic pathway is associated with several disorders,including vulner-ability to viral infections,inflammation,and cancer progression.In particular,the interplay between lung adenocarcinoma(LUAD)and viral infections appears to exist in association with the deregulation of IFN-γsignaling.In this mini-review,we investigated the status of the IFN-γsignaling pathway and the expression level of its components in LUAD.Interestingly,a reduction in IFNGR1 expression seems to be associated with LUAD progression,affecting defenses against viruses such as severe acute respiratory syndrome coronavirus 2.In addition,alterations in the expression of IFNGR1 may inhibit the antiproliferative action of IFN-γsignaling in LUAD.展开更多
Background:Lung Adenocarcinoma(LUAD)is the leading cause of death from lung cancer.Cuproptosis is the latest discovered way of programmed cell death,and Cuproptosis-Related Gene(CRG)is associated with the risk of LUAD...Background:Lung Adenocarcinoma(LUAD)is the leading cause of death from lung cancer.Cuproptosis is the latest discovered way of programmed cell death,and Cuproptosis-Related Gene(CRG)is associated with the risk of LUAD.At present,there are few research of LUAD and Cuproptosis focuses on Long non-coding RNA(LncRNA).As genomics advances,LncRNA emerges as a potential target for understanding tumor progression and prognosis,offering prospects for biological targeted therapy.Therefore,this study provides new biomarkers and therapeutic targets for LUAD from the perspective of LncRNA.Methods:Gene expression,clinical outcome and gene mutation data of LUAD patients were downloaded from TCGA database.Spearman correlation was used to analyze the correlation between LncRNA and CRG.Univariate Cox,multivariate Cox and LASSO Cox regression analysis were used to construct a prognostic model of Cuproptosis-LncRNAs.GO and KEGG enrichment and immune function analysis were performed on differentially expressed genes between different risk groups.Then,immune escape analysis was performed on LUAD patients with different TIDE score.Finally,drug sensitivity analysis was performed on these differentially expressed genes.Results:A total of 2244 Cuproptosis-LncRNAs were found.Through the application of univariate Cox regression analysis,multivariate Cox regression analysis,and LASSO Cox regression analysis,a prognostic model was developed,integrating 15 Cuproptosis-LncRNAs to assess the risk of mortality.Following that,the model underwent assessment through risk score analysis,Kaplan-Meier survival analysis,risk distribution,and evaluation of survival outcomes.The results revealed an AUC value of 0.755 for the model,surpassing the AUC of other clinical pathological features.The results of KEGG analysis showed that the differentially expressed genes in different model groups were mainly involved in Amoebiasis,Fat digestion and absorption,and other signaling pathways.The results of TMB showed that the prognostic model of TMB combined with risk score could well evaluate the prognosis of patients.The TIDE scores did not exhibit a notable distinction between the two risk models.Analysis of drug sensitivity revealed that individuals in the low-risk category demonstrated greater responsiveness to 5-Fluorouracil,Axitinib,Bexarotene,and other drugs compared to those in the high-risk group.Conclusion:Our research offers a valuable reference for predicting the prognosis of LUAD,contributing to a better understanding of the future elucidation of the process and mechanism of Cuproptosis-LncRNAs in LUAD.展开更多
Objective:Lung adenocarcinoma exhibits diverse genetic and morphological backgrounds,in addition to considerable differences in clinical pathology and molecular biological characteristics.Among these,the phenomenon of...Objective:Lung adenocarcinoma exhibits diverse genetic and morphological backgrounds,in addition to considerable differences in clinical pathology and molecular biological characteristics.Among these,the phenomenon of spread through air space(STAS),a distinct mode of lung cancer infiltration,has rarely been reported.Therefore,this study aimed to explore the relationship between STAS tumor cells and the clinical and molecular characteristics of patients with lung adenocarcinoma,as well as their impact on prognosis.Methods:This study included 147 patients who were diagnosed with lung adenocarcinoma at the Inner Mongolia Autonomous Region Cancer Institute between January 2014 and December 2017.Surgical resection specimens were retrospectively analyzed.Using univariate and multivariate Cox analyses,we assessed the association between STAS and the clinicopathological features and molecular characteristics of patients with lung adenocarcinoma.Furthermore,we investigated the effects on patient prognosis.In addition,we developed a column–line plot prediction model and performed internal validation.Results:Patients with positive STAS had a significantly higher proportion of tumors with a diameter≥2 cm,with infiltration around the pleura,blood vessels,and nerves,and a pathological stage>IIB than in STAS-negative patients(P<0.05).Cox multivariate survival analysis revealed that clinical stage,STAS status,tumor size,and visceral pleural invasion were independent prognostic factors influencing the 5-year progression-free survival in patients with lung adenocarcinoma.The predictive values and P values from the Hosmer-Lemeshow test were 0.8 and 0.2,respectively,indicating no statistical difference.Receiver operating characteristic curve analysis demonstrated areas under the curve of 0.884 and 0.872 for the training and validation groups,respectively.The nomogram model exhibited the best fit with a value of 192.09.Conclusions:Clinical stage,pleural invasion,vascular invasion,peripheral nerve invasion,tumor size,and necrosis are independent prognostic factors for patients with STAS-positive lung adenocarcinoma.The nomogrambased on the clinical stage,pleural invasion,vascular invasion,peripheral nerve invasion,tumor size,and necrosis showed good accuracy,differentiation,and clinical practicality.展开更多
Objective:To investigate the genetic correlations between epithelial growth factor receptor(EGFR)mutation and FHIT methylation in patients diagnosed with lung adenocarcinoma(AC)and pulmonary tuberculosis(TB).Methods:T...Objective:To investigate the genetic correlations between epithelial growth factor receptor(EGFR)mutation and FHIT methylation in patients diagnosed with lung adenocarcinoma(AC)and pulmonary tuberculosis(TB).Methods:The presence of EGFR mutations and the methylation status of the FHIT gene in patients presenting with AC and TB were analyzed.The correlation between TB status and the observed genetic and epigenetic variations was also examined.Results:Among the 90 patients included in the study,38 exhibited EGFR mutations(14 among those with TB and 24 among those without TB),while 29 exhibited FHIT myelination(19 among those with TB and 10 among those without TB).Furthermore,the protein expression levels of EGFR and FHIT were significantly higher in patients diagnosed solely with AC compared to those presenting with both AC and TB.A robust inverse correlation was identified between TB status and the frequency of EGFR mutation(P<0.001).Moreover,significant associations were observed between TB status and FHIT methylation(P<0.01).Conclusion:The findings suggest a correlation between TB and the prevalence of EGFR mutation and FHIT methylation in the pathogenesis of AC.展开更多
Lung adenocarcinoma (LUAD) is the most common and deadliest subtype of lung cancer. To select moretargeted and effective treatments for individuals, further advances in classifying LUAD are urgently needed. Thenumber,...Lung adenocarcinoma (LUAD) is the most common and deadliest subtype of lung cancer. To select moretargeted and effective treatments for individuals, further advances in classifying LUAD are urgently needed. Thenumber, type, and function of T cells in the tumor microenvironment (TME) determine the progression andtreatment response of LUAD. Long noncoding RNAs (lncRNAs), may regulate T cell differentiation, development,and activation. Thus, our aim was to identify T cell-related lncRNAs (T cell-Lncs) in LUAD and to investigatewhether T cell-Lncs could serve as potential stratifiers and therapeutic targets. Seven T cell-Lncs were identified tofurther establish the T cell-related lncRNA risk score (TRS) in LUAD. Low TRS individuals were characterized byrobust immune status, fewer genomic alterations, and remarkably longer survival than high TRS individuals. Theexcellent accuracy of TRS in predicting overall survival (OS) was validated in the TCGA-LUAD training cohort andthe GEO-LUAD validation cohort. Our data demonstrated the favorable predictive power of the TRS-basednomogram, which had important clinical significance in estimating the survival probability for individuals. Inaddition, individuals with low TRS could respond better to chemotherapy and immunotherapy than those with highTRS. LINC00525 was identified as a valuable study target, and the ability of LUAD to proliferate or invade wassignificantly attenuated by downregulation of LINC00525. In conclusion, the TRS established by T cell-Lncs couldunambiguously classify LUAD patients, predict their prognosis and guide their management. Moreover, our identifiedT cell-Lncs could provide potential therapeutic targets for LUAD.展开更多
The PRR11 gene(Proline Rich 11)has been implicated in lung cancer;however,relationship between PRR11 and immune infiltration is not clearly understood.In this study,we used The Cancer Genome Atlas(TCGA)data to analyze...The PRR11 gene(Proline Rich 11)has been implicated in lung cancer;however,relationship between PRR11 and immune infiltration is not clearly understood.In this study,we used The Cancer Genome Atlas(TCGA)data to analyze the lung adenocarcinoma patients;PRR11 gene expression,clinicopathological findings,enrichment,and immune infiltration were also studied.PRR11immune response expression assays in lung adenocarcinoma(LUAD)were performed using TIMER,and statistical analysis and visualization were conducted using R software.All data were verified using Gene Expression Profiling Interactive Analysis(GEPIA),and the Human Protein Atlas(HPA).We found that PRR11 was an important prognostic factor in patients with LUAD.PRR11 expression was correlated with tumor stage and progression.Gene Set Enrichment Analysis(GSEA)showed that PRR11was enriched in the cell cycle regulatory pathways.Immune infiltration analysis revealed that the number of T helper 2(Th2)cells increased when PRR11 was overexpressed.These results confirm the role of PRR11 as a prognostic marker of lung adenocarcinoma by controlling the cell cycle and influencing the immune system to facilitate lung cancer progression.展开更多
基金Basic Research Foundation for Universities of the CPC Central Committee(No.2042021KF0081)Innovation Group of Natural Science Foundation of Hubei Province(2020CFA027)。
文摘Objective:To investigate the effects of Eriocitrin on the proliferation and migration of Lung adenocarcinoma(LUAD)cells A549 and H1299,and the mechanism of Epithelial-Mesenchymal Transition(EMT).Methods:The effects of different Eriocitrin on the proliferation of LUAD cells A549 and H1299 were examined by CCK8 method.EMT-associated epithelial calmodulin(E-cadherin and N-cadherin),vimentin,ferroptosis-associated protein SLC7A11,GPX4,FTH were detected by Western Blot and expression of mRNA of EMT marker molecules E-cadherin,N-cadherin,Snail were detected by qRT-PCR.Effects of saccharomyces cerevisiae suberin on ferroptosis in LUAD cells as observed by lipid reactive oxygen species(ROS)assay.Results:Eriocitrin could significantly inhibit the proliferative behavior of LUAD cells A549 and H1299 and showed a certain dose-and time-dependence.Compared with the control group,different concentrations of Eriocitrin could significantly reduce the scratch healing rate after 24 and 48 h of action,and the difference was statistically significant(P<0.01).The expression of ROS is increased,EMT-related protein E-cadherin was increased in LUAD cells A549 and H1299 compared with the control group after the intervention with Eriocitrin.N-cadherin and Vimentin expression was decreased.E-cadherin mRNA expression was increased,and N-cadherin,Snail mRNA expression was decreased,expression of ferroptosis-associated protein SLC7A11,GPX4,FTH was decreased,the difference was statistically significant(P<0.05).Conclusion:Eriocitrin may inhibit the proliferation and migration of LUAD cells by regulating the EMT pathway and has potential application in LUAD prevention and adjuvant chemotherapy.
文摘Objective: Radiotherapy has been widely used to treat lung cancer. However, non-small lung cancer cells are insensitive to radiation, diminishing their radiotherapy effects. Although the radiosensitivity of the non-small lung cancer cells was reported to be enhanced through regulating miR-34a, the regulation effects of miR-34a expression on radiosensitivity of lung adenocarcinoma cells through target genes CDK4, CDK6, CyclinD1, and Bcl-2/Bax have not been systematically investigated. Methods: In this study, we investigated the effect of miR-34a expression on the Bcl-2, CDK4, and CDK6 pathways in lung adenocarcinoma cells, to provide new insights into the sensitization treatment of lung cancer. We first studied the effect of miR-34a expression on H1299 and A549 cell activity. Then to investigate the mechanisms of radiosensitivity, we focused on apoptosis, cell cycle, and target genes. Results: We find that overexpression of miR-34a in lung adenocarcinoma cells inhibits cell activity, and improves radiosensitivity. Specifically, overexpression of miR-34a suppresses the expression of target genes CDK4, CDK6, CyclinD1, and Bcl-2/Bax, which leads to cell cycle arrest and promotes apoptosis of lung adenocarcinoma cells. Conclusions: Overall, our results demonstrate that the overexpression of miR-34a enhances the radiosensitivity of lung adenocarcinoma cells, indicating that miR-34a is a sensitizer for lung adenocarcinoma radiotherapy.
基金supported by Lebanese University for the financial support of this work(Project M.Nasser UL2017)
文摘Objective: To test the coalescence effect of two chemotherapy drugs at low effective dose(cisplatin and taxotere) combined with pomegranate juice on A549 cancer cells. Methods: Infrared spectroscopy method is a qualitative test that was performed to ensure the existence of the phytochemicals providing the antioxidant activity through the presence of the hydroxyl group(-OH). The viability of A549 cell line and normal MCs was tested using the neutral red uptake, Clonogenic survival, XTT and Cell migration assays. Results: Our results showed that this combination firstly led to a greater decrease in the viability of cells comparing to those treated with chemotherapy drugs alone, and secondly led to a significant reduction in cell migration. Conclusions: These data suggest a synergistic effect between the pomegranate and cisplatin which makes probably this combination a powerful option for treating lung adenocarcinoma and in parallel minimizing the systemic side effects.
基金This work was supported by the NationalNatural Science Foundation of China (No.30371624).
文摘Objective: Her-2/neu protein overexpression has been demonstrated in Non-small cell lung cancer, especially in lung adenocarcinoma. Its overexpression often indicates a poor prognosis. Therapeutic agents against her-2/neu have been intensively sought over the past decades. The objective of this paper is to investigate the effect of chemically synthesized siRNA targeting her-2/neu on her-2/neu dysregulated human lung adenocarcinoma cells. Methods: Calu-3 cells were transfected with siRNAs formulated LipofectAMINE 2000. The her-2/neu mRNA and protein levels were detected by RT-PCR and flow cytometry (FCM). The biological morphology and growth inhibition of calu-3 cells were observed with light microscopy and MTT assay, respectively. The cell cycle and apoptosis rate were analyzed by FCM. Results: siRNA targeting Her-2/neu down-regulated the transcription of her-2/neu oncogene and protein level. Slowed cell proliferation and cell cycle arrest at G0/1 stage could be also observed, accompanied with enhanced cell apoptosis. Conclusion: Specific siRNA targeting her-2/neu can effectively inhibit her-2/neu expression in her-2/neu overexpressing calu-3 cell lines. siRNA-mediated gene silencing may be a useful therapeutic strategy for cancer.
文摘Using FX-4000 strain unit, the prolieration in human lung adenocarcinoma A549 cells that underwent mechanical strain of different waveform、frequency and duration were studied. Image analysis revealed that cellular proliferation rate(PR) reduced significantly after cells were subjected to square wave with 0～20% elongation at frequency 30,40,50 and 60 cycles/min for 2h. The PR had no distinct difference at heart wave , triangle wave and sine wave group compared with control. It is concluded that square wave and higher frequency play an important role in inhibiting A549 cells proliferation.
基金supported in 2015 by a research grant from Chungbuk National University
文摘The use of anti-beta 1 integrin monoclonal antibody in lung cancer treatment has proven beneficial.Here,we developed a novel monoclonal antibody(mAb),called P5,by immunizing mice with human peripheral blood mononuclear cells(PBMC).Its anti-tumor effect is now being tested,in a clinical phase HI trial,in combinatorial treatments with various chemical drugs.To confirm that P5 indeed binds to beta 1 integrin,cell lysates were immunoprecipitated with commercial anti-beta 1 integrin mAb(TS2/16) and immunoblotted against P5 to reveal a140 kDa molecular weight band,as expected.Immunoprecipitation with P5 followed by LC/MS protein sequence analysis further verified P5 antigen to be beta 1 integrin.Cisplatin treatment upregulated cell surface expression of beta 1 integrin in A549 cells,while causing inhibition of cell growth.When cells were co-treated with different concentrations of P5 mAb,the cisplatin-mediated inhibitory effect was enhanced in a dose-dependent manner.Our findings show that a combinatorial treatment of P5 mAb and cisplatin in A549 cells resulted in a 30%increase in apoptosis,compared to baseline,and significantly more when compared to either the cisplatin or P5 alone group.The entire peptide sequences in CDR from variable region of Ig heavy and light chain gene for P5 mAb are also disclosed.Together,these results provide evidence of the beneficial effect of P5 mAb in combinatorial treatment of human lung adenocarcinoma.
文摘Background:Cytotoxic T lymphocytes(CD8+T)cells function critically in mediating anti-tumor immune response in cancer patients.Characterizing the specific functions of CD8+T cells in lung adenocarcinoma(LUAD)could help better understand local anti-tumor immune responses and estimate the effect of immunotherapy.Methods:Gens related to CD8+T cells were identified by cluster analysis based on the single-cell sequencing data of three LUAD tissues and their paired normal tissues.Weighted gene co-expression network analysis(WGCNA),consensus clustering,differential expression analysis,least absolute shrinkage and selection operator(LASSO)and Cox regression analysis were conducted to classify molecular subtypes for LUAD and to develop a risk model using prognostic genes related to CD8+T cells.Expression of the genes in the prognostic model,their effects on tumor cell invasion,and interactions with CD8+T cells were verified by cell experiments.Results:This study defined two LUAD clusters(CD8+0 and CD8+1)based on CD8+T cells,with cluster CD8+0 being significantly associated with the prognosis of LUAD.Three heterogeneous subtypes(clusters 1,2,and 3)differing in prognosis,genome mutation events,and immune status were categorized using 42 prognostic genes.A prognostic model created based on 11 significant genes(including CD200R1,CLEC17A,ZC3H12D,GNG7,SNX30,CDCP1,NEIL3,IGF2BP1,RHOV,ABCC2,and KRT81)was able to independently estimate the death risk for patients in different LUAD cohorts.Moreover,the model also showed general applicability in external validation cohorts.Low-risk patients could benefit more from taking immunotherapy and were significantly related to the resistance to anticancer drugs.The results from cell experiments demonstrated that the expression of CD200R1,CLEC17A,ZC3H12D,GNG7,and SNX30 was significantly downregulated,while that of CDCP1,NEIL3,IGF2BP1,RHOV,ABCC2 and KRT81 was upregulated in LUAD cells.Inhibition of CD200R1 greatly increased the invasiveness of the LUAD cells,but inhibiting CDCP1 expression weakened the invasion ability of LUAD cells.Conclusion:This study defined two prognostic CD8+T cell clusters and classified three heterogeneous molecular subtypes for LUAD.A prognostic model predictive of the potential effects of immunotherapy on LUAD patients was developed.
基金supported by the Natural Science Foundation of Hubei Province(no.2021CFB372 to Hua Xiong).
文摘Lung cancer is the leading cause of cancer-related deaths globally.In recent years,with the widespread use of genetic testing,epidermal growth factor receptor–tyrosine kinase inhibitor(EGFR-TKI)–targeted drugs have been efficacious to patients with lung adenocarcinoma exhibiting EGFR mutations.However,resistance to treatment is inevitable and eventually leads to tumor progression,recurrence,and reduction in the overall treatment efficacy.Lung cancer stem cells play a crucial role in the development of resistance toward EGFR-TKI–targeted therapy for lung adenocarcinoma.Lung cancer stem cells possess self-renewal,multilineage differentiation,and unlimited proliferation capabilities,which efficiently contribute to tumor formation and ultimately lead to tumor recurrence andmetastasis.In this study,we evaluated the origin,markers,stemness index,relevant classic studies,resistance mechanisms,related signaling pathways,and strategies for reversing lung cancer stem cell resistance to EGFR-TKIs to provide new insights on delaying or reducing resistance and to improve the treatment efficacy of patients with EGFR-mutated lung adenocarcinoma in the future.
基金National Natural Science Foundation of China(Grant No.81273297)Shenyang Science and Technology Plan.Public Health R&D Special Project(21-173-9-67).
文摘Advanced LUAD shows limited response to treatment including immune therapy.With the development of sequencing omics,it is urgent to combine high-throughput multi-omics data to identify new immune checkpoint therapeutic response markers.Using GSE72094(n=386)and GSE31210(n=226)gene expression profile data in the GEO database,we identified genes associated with lung adenocarcinoma(LUAD)death using tools such as“edgeR”and“maftools”and visualized the characteristics of these genes using the“circlize”R package.We constructed a prognostic model based on death-related genes and optimized the model using LASSO-Cox regression methods.By calculating the cell death index(CDI)of each individual,we divided LUAD patients into high and low CDI groups and examined the relationship between CDI and overall survival time by principal component analysis(PCA)and Kaplan-Meier analysis.We also used the“ConsensusClusterPlus”tool for unsupervised clustering of LUAD subtypes based on model genes.In addition,we collected data on the expression of immunomodulatory genes and model genes for each cohort and performed tumor microenvironment analyses.We also used the TIDE algorithm to predict immunotherapy responses in the CDI cohort.Finally,we studied the effect of PRKCD on the proliferation and migration of LUAD cells through cell culture experiments.The study utilized the TCGA-LUAD cohort(n=493)and identified 2,901 genes that are differentially expressed in patients with LUAD.Through KEGG and GO enrichment analysis,these genes were found to be involved in a wide range of biological pathways.The study also used univariate Cox regression models and LASSO regression analyses to identify 17 candidate genes that were best associated with mortality prognostic risk scores.By comparing the overall survival(OS)outcomes of patients with different CDI values,it was found that increased CDI levels were significantly associated with lower OS rates.In addition,the study used unsupervised cluster analysis to divide 115 LUAD patients into two distinct clusters with significant differences in OS timing.Finally,a prognostic indicator called CDI was established and its feasibility as an independent prognostic indicator was evaluated by Cox proportional risk regression analysis.The immunotherapy efficacy was more sensitive in the group with high expression of programmed cell death models.Relationship between programmed cell death(PCD)signature models and drug reactivity.After evaluating the median inhibitory concentration(IC50)of various drugs in LUAD samples,statistically significant differences in IC50 values were found in cohorts with high and low CDI status.Specifically,Gefitinib and Lapatinib had higher IC50 values in the high-CDI cohort,while Olaparib,Oxaliplatin,SB216763,and Axitinib had lower values.These results suggest that individuals with high CDI levels are sensitive to tyrosine kinase inhibitors and may be resistant to conventional chemotherapy.Therefore,this study constructed a gene model that can evaluate patient immunotherapy by using programmed cell death-related genes based on muti-omics.The CDI index composed of these programmed cell death-related genes reveals the heterogeneity of lung adenocarcinoma tumors and serves as a prognostic indicator for patients.
基金supported by the National Natural Science Foundation of China(No.81703001)the Natural Science Foundation of Hebei Province(No.H2021406021),Hebei Province Medical Science Research Project(Nos.20210247,20221335)Hebei Province Government-Funded Clinical Medical Outstanding Talents Project,Chengde Medical University Scientific Research Major Projects(No.KY2020005).
文摘The platinum-based chemotherapy is one of the most frequently used treatment protocols for lung adenocarcinoma(LUAD),and chemoresistance,however,usually results in treatment failure and limits its application in the clinic.It has been shown that microRNAs(miRNAs)play a significant role in tumor chemoresistance.In this study,miR-125b was identified as a specific cisplatin(DDP)-resistant gene in LUAD,as indicated by the bioinformatics analysis and the real-time quantitative PCR assay.The decreased serum level of miR-125b in LUAD patients was correlated with the poor treatment response rate and short survival time.MiR-125b decreased the A549/DDP proliferation,and the multiple drug resistance-and autophagy-related protein expression levels,which were all reversed by the inhibition of miR-125b.In addition,xenografts of human tumors in nude mice were suppressed by miR-125b,demonstrating that through autophagy regulation,miR-125b could reverse the DDP resistance in LUAD cells,both in vitro and in vivo.Further mechanistic studies indicated that miR-125b directly repressed the expression levels of RORA and its downstream BNIP3L,which in turn inhibited autophagy and reversed chemoresistance.Based on these findings,miR-125b in combination with DDP might be an effective treatment option to overcome DDP resistance in LUAD.
文摘Dear Editor,Lung adenocarcinoma with choroidal metastasis is a common form of cancer,with breast cancer accounting for 40%-53%and lung cancer accounting for 20%-29%of primary cases with choroidal metastases[1].This type of metastatic cancer typically affects people aged 40-70y,and is more prevalent in women than men[1].Ocular symptoms,including vision loss,can be an early indication of the disease,as many tumors are asymptomatic in their early stages.Studies have shown that 40.3%of cases involve the macular region,which explains why ocular symptoms are often the first manifestation of the disease[2].When choroidal metastasis is suspected in patients without a history of cancer,a combination of diagnostic tools should be used to identify the primary source of the tumor.Choroidal tumors can serve as an indication of future lung cancer diagnosis in some patients with lung cancer[1].In this report,we present a case of bilateral lung adenocarcinoma where ocular symptoms were the first indication of the disease.
文摘Background:The aberrant intraellular expression of a mitochondrial aspartyl tRNA synthetase 2(DARS2)has been reported in human cancers.Nevertheless its critical role and detailed mechanism in lung adenocarcinoma(LUAD)remain unexplored.Methods:Initially,The Cancer Genome Atlas(TCGA)based Gene Expression Profiling Interactive Analysis(GEPIA)database (http:/gepia.cancer-pku.cn/)was used to analyze the prognostic relevance of DARS2 expression in LUAD.Further,cell counting kit(CCK)8,immunostaining,and transwell invasion assays in LUAD cell lines in vitro,as well as DARS2 silence on LUAD by tumorigenicity experiments in wivo in nude mice,were performed.Besides,we analyzed the expression levels of p-PI3K(phosphorylated Phosphotylinosital3 kinase),PI3K,AKT(Protein Kinase B),p-AKT(phosphorylated Protein Kinase B),PCNA(proliferating cell nudear antigen),cleaved-caspase 3,E cadherin,and N-cadherin proteins using the Westem blot analysis.Results:LUAD tissues showed higher DARS2 expression compared to normal tissues.Upregulation of DARS2 could be related to Tumor-Node-Metastasis(TNM)stage,high lymph node metastasis,and inferior prognosis.DARS2 silence decreased the proliferation,migration,and invasion abilities of LUAD cells.In addition,the DARS2 downregulation decreased the PCNA and N-cadherin expression and increased cleaved:caspase 3 and E cadherin expressions in LUAD cells,coupled with the inactivation of the PI3K/AKT signaling pathway.Moreover,DARS2 silence impaired the tumonigenicity of LUAD in vivo.Interestingly,let:7b-5p could recognize DARS2 through a complementary sequence.Mechanistically,the increased let 7b 5p expression attenuated the promo oncogenic action of DARS2 during LUAD progression,which were inversely correlated to each other in the LUAD tssues Conclusion:In summary,let 7b-5p,downregulated DARS2 expression,regulating the progression of LUAD cells by the PI3K/AKT signaling pathway.
文摘BACKGROUND Heat shock protein A4(HSPA4)belongs to molecular chaperone protein family which plays important roles within variable cellular activities,including cancer initiation and progression.However,the prognostic and immunological significance of HSPA4 in lung adenocarcinoma(LUAD)has not been revealed yet.AIM To explore the prognostic and immunological roles of HSPA4 to identify a novel prognostic biomarker and therapeutic target for LUAD.METHODS We assessed the prognostic and immunological significance of HSPA4 in LUAD using data from The Cancer Genome Atlas database.The association between HSPA4 expression and clinical-pathological features was assessed through Kruskal-Wallis and Wilcoxon signed-rank test.Univariate/multivariate Cox regression analyses and Kaplan-Meier curves were employed to evaluate prognostic factors,including HSPA4,in LUAD.Gene set enrichment analysis(GSEA)was conducted to identify the key signaling pathways associated with HSPA4.The correlation between HSPA4 expression and cancer immune infiltration was evaluated using single-sample gene set enrichment analysis(ssGSEA).RESULTS Overexpressing HSPA4 was significantly related to advanced pathologic TNM stage,advanced pathologic stage,progression disease status of primary therapy outcome and female subgroups with LUAD.In addition,increased HSPA4 expression was found to be related to worse disease-specific survival and overall survival.GSEA analysis indicated a significant correlation between HSPA4 and cell cycle regulation and immune response,particularly through diminishing the function of cytotoxicity cells and CD8 T cells.The ssGSEA algorithm showed a positive correlation between HSPA4 expression and infiltrating levels of Th2 cells,while a negative correlation was observed with cytotoxic cell infiltration levels.CONCLUSION Our findings indicate HSPA4 is related to prognosis and immune cell infiltrates and may act as a novel prognostic biomarker and therapeutic target for LUAD.
文摘Interferon-gamma(IFN-γ)plays a dual role in cancer;it is both a pro-and an antitumorigenic cytokine,depending on the type of cancer.The deregulation of the IFN-γcanonic pathway is associated with several disorders,including vulner-ability to viral infections,inflammation,and cancer progression.In particular,the interplay between lung adenocarcinoma(LUAD)and viral infections appears to exist in association with the deregulation of IFN-γsignaling.In this mini-review,we investigated the status of the IFN-γsignaling pathway and the expression level of its components in LUAD.Interestingly,a reduction in IFNGR1 expression seems to be associated with LUAD progression,affecting defenses against viruses such as severe acute respiratory syndrome coronavirus 2.In addition,alterations in the expression of IFNGR1 may inhibit the antiproliferative action of IFN-γsignaling in LUAD.
文摘Background:Lung Adenocarcinoma(LUAD)is the leading cause of death from lung cancer.Cuproptosis is the latest discovered way of programmed cell death,and Cuproptosis-Related Gene(CRG)is associated with the risk of LUAD.At present,there are few research of LUAD and Cuproptosis focuses on Long non-coding RNA(LncRNA).As genomics advances,LncRNA emerges as a potential target for understanding tumor progression and prognosis,offering prospects for biological targeted therapy.Therefore,this study provides new biomarkers and therapeutic targets for LUAD from the perspective of LncRNA.Methods:Gene expression,clinical outcome and gene mutation data of LUAD patients were downloaded from TCGA database.Spearman correlation was used to analyze the correlation between LncRNA and CRG.Univariate Cox,multivariate Cox and LASSO Cox regression analysis were used to construct a prognostic model of Cuproptosis-LncRNAs.GO and KEGG enrichment and immune function analysis were performed on differentially expressed genes between different risk groups.Then,immune escape analysis was performed on LUAD patients with different TIDE score.Finally,drug sensitivity analysis was performed on these differentially expressed genes.Results:A total of 2244 Cuproptosis-LncRNAs were found.Through the application of univariate Cox regression analysis,multivariate Cox regression analysis,and LASSO Cox regression analysis,a prognostic model was developed,integrating 15 Cuproptosis-LncRNAs to assess the risk of mortality.Following that,the model underwent assessment through risk score analysis,Kaplan-Meier survival analysis,risk distribution,and evaluation of survival outcomes.The results revealed an AUC value of 0.755 for the model,surpassing the AUC of other clinical pathological features.The results of KEGG analysis showed that the differentially expressed genes in different model groups were mainly involved in Amoebiasis,Fat digestion and absorption,and other signaling pathways.The results of TMB showed that the prognostic model of TMB combined with risk score could well evaluate the prognosis of patients.The TIDE scores did not exhibit a notable distinction between the two risk models.Analysis of drug sensitivity revealed that individuals in the low-risk category demonstrated greater responsiveness to 5-Fluorouracil,Axitinib,Bexarotene,and other drugs compared to those in the high-risk group.Conclusion:Our research offers a valuable reference for predicting the prognosis of LUAD,contributing to a better understanding of the future elucidation of the process and mechanism of Cuproptosis-LncRNAs in LUAD.
基金Funded by the Health Science and Technology Program of Inner Mongolia Autonomous Region(no.202201061)Supported by the Joint Project of theMillion Science and Technology Initiatives of Inner Mongolia Medical University(no.YKD2020KJBW(LH)057).
文摘Objective:Lung adenocarcinoma exhibits diverse genetic and morphological backgrounds,in addition to considerable differences in clinical pathology and molecular biological characteristics.Among these,the phenomenon of spread through air space(STAS),a distinct mode of lung cancer infiltration,has rarely been reported.Therefore,this study aimed to explore the relationship between STAS tumor cells and the clinical and molecular characteristics of patients with lung adenocarcinoma,as well as their impact on prognosis.Methods:This study included 147 patients who were diagnosed with lung adenocarcinoma at the Inner Mongolia Autonomous Region Cancer Institute between January 2014 and December 2017.Surgical resection specimens were retrospectively analyzed.Using univariate and multivariate Cox analyses,we assessed the association between STAS and the clinicopathological features and molecular characteristics of patients with lung adenocarcinoma.Furthermore,we investigated the effects on patient prognosis.In addition,we developed a column–line plot prediction model and performed internal validation.Results:Patients with positive STAS had a significantly higher proportion of tumors with a diameter≥2 cm,with infiltration around the pleura,blood vessels,and nerves,and a pathological stage>IIB than in STAS-negative patients(P<0.05).Cox multivariate survival analysis revealed that clinical stage,STAS status,tumor size,and visceral pleural invasion were independent prognostic factors influencing the 5-year progression-free survival in patients with lung adenocarcinoma.The predictive values and P values from the Hosmer-Lemeshow test were 0.8 and 0.2,respectively,indicating no statistical difference.Receiver operating characteristic curve analysis demonstrated areas under the curve of 0.884 and 0.872 for the training and validation groups,respectively.The nomogram model exhibited the best fit with a value of 192.09.Conclusions:Clinical stage,pleural invasion,vascular invasion,peripheral nerve invasion,tumor size,and necrosis are independent prognostic factors for patients with STAS-positive lung adenocarcinoma.The nomogrambased on the clinical stage,pleural invasion,vascular invasion,peripheral nerve invasion,tumor size,and necrosis showed good accuracy,differentiation,and clinical practicality.
文摘Objective:To investigate the genetic correlations between epithelial growth factor receptor(EGFR)mutation and FHIT methylation in patients diagnosed with lung adenocarcinoma(AC)and pulmonary tuberculosis(TB).Methods:The presence of EGFR mutations and the methylation status of the FHIT gene in patients presenting with AC and TB were analyzed.The correlation between TB status and the observed genetic and epigenetic variations was also examined.Results:Among the 90 patients included in the study,38 exhibited EGFR mutations(14 among those with TB and 24 among those without TB),while 29 exhibited FHIT myelination(19 among those with TB and 10 among those without TB).Furthermore,the protein expression levels of EGFR and FHIT were significantly higher in patients diagnosed solely with AC compared to those presenting with both AC and TB.A robust inverse correlation was identified between TB status and the frequency of EGFR mutation(P<0.001).Moreover,significant associations were observed between TB status and FHIT methylation(P<0.01).Conclusion:The findings suggest a correlation between TB and the prevalence of EGFR mutation and FHIT methylation in the pathogenesis of AC.
基金supported by the following funds:the Key Research and Development Project of the Science and Technology Department of Sichuan Province(Grant Nos.2021YFS0202 and 2021YFS0229)the Natural Science Foundation of Sichuan Province(Grant No.2022NSFSC1326)+1 种基金Postdoctoral Research Fund of West China Hospital(Grant Nos.2019HXBH056 and 2020HXBH066)China Postdoctoral Science Foundation(Grant No.2022T150454).
文摘Lung adenocarcinoma (LUAD) is the most common and deadliest subtype of lung cancer. To select moretargeted and effective treatments for individuals, further advances in classifying LUAD are urgently needed. Thenumber, type, and function of T cells in the tumor microenvironment (TME) determine the progression andtreatment response of LUAD. Long noncoding RNAs (lncRNAs), may regulate T cell differentiation, development,and activation. Thus, our aim was to identify T cell-related lncRNAs (T cell-Lncs) in LUAD and to investigatewhether T cell-Lncs could serve as potential stratifiers and therapeutic targets. Seven T cell-Lncs were identified tofurther establish the T cell-related lncRNA risk score (TRS) in LUAD. Low TRS individuals were characterized byrobust immune status, fewer genomic alterations, and remarkably longer survival than high TRS individuals. Theexcellent accuracy of TRS in predicting overall survival (OS) was validated in the TCGA-LUAD training cohort andthe GEO-LUAD validation cohort. Our data demonstrated the favorable predictive power of the TRS-basednomogram, which had important clinical significance in estimating the survival probability for individuals. Inaddition, individuals with low TRS could respond better to chemotherapy and immunotherapy than those with highTRS. LINC00525 was identified as a valuable study target, and the ability of LUAD to proliferate or invade wassignificantly attenuated by downregulation of LINC00525. In conclusion, the TRS established by T cell-Lncs couldunambiguously classify LUAD patients, predict their prognosis and guide their management. Moreover, our identifiedT cell-Lncs could provide potential therapeutic targets for LUAD.
基金supported by the Traditional Chinese Medicine Science and Technology Project of Shandong Province [grant number 2020Q139]。
文摘The PRR11 gene(Proline Rich 11)has been implicated in lung cancer;however,relationship between PRR11 and immune infiltration is not clearly understood.In this study,we used The Cancer Genome Atlas(TCGA)data to analyze the lung adenocarcinoma patients;PRR11 gene expression,clinicopathological findings,enrichment,and immune infiltration were also studied.PRR11immune response expression assays in lung adenocarcinoma(LUAD)were performed using TIMER,and statistical analysis and visualization were conducted using R software.All data were verified using Gene Expression Profiling Interactive Analysis(GEPIA),and the Human Protein Atlas(HPA).We found that PRR11 was an important prognostic factor in patients with LUAD.PRR11 expression was correlated with tumor stage and progression.Gene Set Enrichment Analysis(GSEA)showed that PRR11was enriched in the cell cycle regulatory pathways.Immune infiltration analysis revealed that the number of T helper 2(Th2)cells increased when PRR11 was overexpressed.These results confirm the role of PRR11 as a prognostic marker of lung adenocarcinoma by controlling the cell cycle and influencing the immune system to facilitate lung cancer progression.
