BACKGROUND Treatment options for patients with gastric cancer(GC)continue to improve,but the overall prognosis is poor.The use of PD-1 inhibitors has also brought benefits to patients with advanced GC and has graduall...BACKGROUND Treatment options for patients with gastric cancer(GC)continue to improve,but the overall prognosis is poor.The use of PD-1 inhibitors has also brought benefits to patients with advanced GC and has gradually become the new standard treatment option at present,and there is an urgent need to identify valuable biomarkers to classify patients with different characteristics into subgroups.AIM To determined the effects of differentially expressed immune-related genes(DEIRGs)on the development,prognosis,tumor microenvironment(TME),and treatment response among GC patients with the expectation of providing new biomarkers for personalized treatment of GC populations.METHODS Gene expression data and clinical pathologic information were downloaded from The Cancer Genome Atlas(TCGA),and immune-related genes(IRGs)were searched from ImmPort.DEIRGs were extracted from the intersection of the differentially-expressed genes(DEGs)and IRGs lists.The enrichment pathways of key genes were obtained by analyzing the Kyoto Encyclopedia of Genes and Genomes(KEGGs)and Gene Ontology(GO)databases.To identify genes associated with prognosis,a tumor risk score model based on DEIRGs was constructed using Least Absolute Shrinkage and Selection Operator and multivariate Cox regression.The tumor risk score was divided into high-and lowrisk groups.The entire cohort was randomly divided into a 2:1 training cohort and a test cohort for internal validation to assess the feasibility of the risk model.The infiltration of immune cells was obtained using‘CIBERSORT,’and the infiltration of immune subgroups in high-and low-risk groups was analyzed.The GC immune score data were obtained and the difference in immune scores between the two groups was analyzed.RESULTS We collected 412 GC and 36 adjacent tissue samples,and identified 3627 DEGs and 1311 IRGs.A total of 482 DEIRGs were obtained.GO analysis showed that DEIRGs were mainly distributed in immunoglobulin complexes,receptor ligand activity,and signaling receptor activators.KEGG pathway analysis showed that the top three DEIRGs enrichment types were cytokine-cytokine receptors,neuroactive ligand receptor interactions,and viral protein interactions.We ultimately obtained an immune-related signature based on 10 genes,including 9 risk genes(LCN1,LEAP2,TMSB15A mRNA,DEFB126,PI15,IGHD3-16,IGLV3-22,CGB5,and GLP2R)and 1 protective gene(LGR6).Kaplan-Meier survival analysis,receiver operating characteristic curve analysis,and risk curves confirmed that the risk model had good predictive ability.Multivariate COX analysis showed that age,stage,and risk score were independent prognostic factors for patients with GC.Meanwhile,patients in the low-risk group had higher tumor mutation burden and immunophenotype,which can be used to predict the immune checkpoint inhibitor response.Both cytotoxic T lymphocyte antigen4+and programmed death 1+patients with lower risk scores were more sensitive to immunotherapy.CONCLUSION In this study a new prognostic model consisting of 10 DEIRGs was constructed based on the TME.By providing risk factor analysis and prognostic information,our risk model can provide new directions for immunotherapy in GC patients.展开更多
Pseudomyxoma peritonei(PMP) is an indolent malignant syndrome. The standard treatment for PMP is cytoreductive surgery combined with intraperitoneal hyperthermic chemotherapy(CRS + HIPEC). However, the high recurrence...Pseudomyxoma peritonei(PMP) is an indolent malignant syndrome. The standard treatment for PMP is cytoreductive surgery combined with intraperitoneal hyperthermic chemotherapy(CRS + HIPEC). However, the high recurrence rate and latent clinical symptoms and signs are major obstacles to further improving clinical outcomes. Moreover, patients in advanced stages receive little benefit from CRS + HIPEC due to widespread intraperitoneal metastases. Another challenge in PMP treatment involves the progressive sclerosis of PMP cell-secreted mucus, which is often increased due to activating mutations in the gene coding for guanine nucleotide-binding protein alpha subunit(GNAS). Consequently, the development of other PMP therapies is urgently needed. Several immune-related therapies have shown promise, including the use of bacterium-derived non-specific immunogenic agents, radioimmunotherapeutic agents, and tumor cell-derived neoantigens, but a well-recognized immunotherapy has not been established. In this review the roles of GNAS mutations in the promotion of mucin secretion and disease development are discussed. In addition, the immunologic features of the PMP microenvironment and immune-associated treatments are discussed to summarize the current understanding of key features of the disease and to facilitate the development of immunotherapies.展开更多
Gastric cancer ranks as the sixth most prevalent cancer worldwide.In recent research within the realm of gastric cancer treatment,the identification and application of immune-related genetic features have emerged as g...Gastric cancer ranks as the sixth most prevalent cancer worldwide.In recent research within the realm of gastric cancer treatment,the identification and application of immune-related genetic features have emerged as groundbreaking advancements.The study by Ma et al,which developed a prognostic model based on 10 genes,categorizes patients into high and low-risk groups to predict their responsiveness to immune checkpoint inhibitor therapy.This research underscores the potential of immune-related genes as biomarkers for personalized treatment,offering insights into tumor mutation burden and immune phenotype scores.We advocate for further validation,understanding of biological mechanisms,and integration of diverse datasets to enhance the model's predictive accuracy and clinical application,marking a significant step towards personalized and precise treatment for gastric cancer.展开更多
We conducted a comprehensive review of existing prediction models pertaining to the efficacy of immune-checkpoint inhibitor(ICI)and the occurrence of immune-related adverse events(irAEs).The predictive potential of ne...We conducted a comprehensive review of existing prediction models pertaining to the efficacy of immune-checkpoint inhibitor(ICI)and the occurrence of immune-related adverse events(irAEs).The predictive potential of neutrophil-to-lymphocyte ratio(NLR)and platelet-to-lymphocyte ratio(PLR)in determining ICI effectiveness has been extensively investigated,while limited research has been conducted on predicting irAEs.Furthermore,the combined model incor-porating NLR and PLR,either with each other or in conjunction with additional markers such as carcinoembryonic antigen,exhibits superior predictive capabilities compared to individual markers alone.NLR and PLR are promising markers for clinical applications.Forthcoming models ought to incorporate established efficacious models and newly identified ones,thereby constituting a multifactor composite model.Furthermore,efforts should be made to explore effective clinical application approaches that enhance the predictive accuracy and efficiency.展开更多
Immune checkpoint inhibitors(ICIs)constitute a pivotal class of immunotherapeutic drugs in cancer treatment.However,their widespread clinical application has led to a notable surge in immune-related adverse events(irA...Immune checkpoint inhibitors(ICIs)constitute a pivotal class of immunotherapeutic drugs in cancer treatment.However,their widespread clinical application has led to a notable surge in immune-related adverse events(irAEs),significantly affecting the efficacy and survival rates of patients undergoing ICI therapy.While conventional hematological and imaging tests are adept at detecting organ-specific toxicities,distinguishing adverse reactions from those induced by viruses,bacteria,or immune diseases remains a formidable challenge.Consequently,there exists an urgent imperative for reliable biomarkers capable of accurately predicting or diagnosing irAEs.Thus,a thorough review of existing studies on irAEs biomarkers is indispensable.Our review commences by providing a succinct over-view of major irAEs,followed by a comprehensive summary of irAEs biomarkers across various dimensions.Furthermore,we delve into innovative methodologies such as machine learning,single-cell RNA sequencing,multiomics analysis,and gut microbiota profiling to identify novel,robust biomarkers that can facilitate precise irAEs diagnosis or prediction.Lastly,this review furnishes a concise exposition of irAEs mechanisms to augment understanding of irAEs prediction,diagnosis,and treatment strategies.展开更多
Purpose research on nursing sensitive indicators in tumor Patients application effect in immune-related skin toxicity management. Method select our hospital April to June, 202360 cases patients with immune therapy set...Purpose research on nursing sensitive indicators in tumor Patients application effect in immune-related skin toxicity management. Method select our hospital April to June, 202360 cases patients with immune therapy settings as the control group. August-October, 2023 60 cases the patients treated with immune therapy were the experimental group. The control group adopted regular nursing methods, while the experimental group sensitive Indicators, evidence-based give preventive care. The social situation, psychological state, physical function, quality of life score, incidence of skin toxicity caused by immune checkpoint inhibitors, moderate and above of the two groups of patients were compared. Incidence of skin toxicity. Result: experience group SAS score, SDS score higher than the control group, the difference was statistically significant (P < 0.05);The incidence of skin toxic reactions caused by immune checkpoint inhibitors and the incidence of moderate and above skin toxic reactions in the experimental group are lower than those in the control group, and the difference is statistically significant (P < 0.05). Conclusion: sensitive indicator guidance evidence-based preventive care can reduce the degree of immune-related skin toxicity, improve the psychological state and quality of life of tumor patients treated with immune therapy and reduce the incidence of adverse reactions, improve nursing quality and patient satisfaction.展开更多
Background:Hepatocellular carcinoma(HCC)appears to be strongly associated with immune-related genes.However,immune-related genes are not well understood as a prognostic marker in HCC caused by the hepatitis B virus(HB...Background:Hepatocellular carcinoma(HCC)appears to be strongly associated with immune-related genes.However,immune-related genes are not well understood as a prognostic marker in HCC caused by the hepatitis B virus(HBV).The purpose of this study was to investigate the prognostic significance of immune-related genes in HBV-infected HCC.Methods:Gene expression data from 114 HBV-infected HCC and 50 normal tissues were integrated into The Cancer Genome Atlas.Differentially expressed immune-associated genes were analyzed to identify immune-associated differential genes associated with overall survival.Least Absolute Shrinkage and Selection Operator and multivariate Cox regressions were used to constructing immunoprognostic models.An independent prognostic factor analysis using multiple Cox regressions was also performed for HBV-infected HCCs.Immunocorrelation analysis markers and immune cell infiltration were also investigated.Results:We found 113 differentially expressed immune-associated genes.Immune-related differential genes were significantly correlated with the overall survival of HCC patients.We constructed an immune-based prognostic model using multivariate Cox regression analysis including seven immune-related genes.According to further analysis,immune-related prognostic factors may serve as independent prognostic indicators in the clinical setting.There is also evidence that the 7-gene prognostic model reflects the tumor immune microenvironment as a result of the risk score model and immune cell infiltration.Conclusions:As a result of our study,we screened immune-related genes for prognosis in HBV-infected HCC and developed a novel immune-based prognostic model.The research not only provides new prognostic biomarkers but also offers insight into the tumor immune microenvironment and lays the theoretical groundwork for immunotherapy.展开更多
BACKGROUND Although immune checkpoint inhibitor(ICI)therapy has improved the prognosis of unresectable hepatocellular carcinoma(HCC),it has also resulted in unique immune-related adverse events(irAEs).The relationship...BACKGROUND Although immune checkpoint inhibitor(ICI)therapy has improved the prognosis of unresectable hepatocellular carcinoma(HCC),it has also resulted in unique immune-related adverse events(irAEs).The relationship between irAE and treatment outcomes in ICI-treated unresectable HCC patients remains unknown.AIM To elucidate the correlation between immune-related toxic effects and prognosis in patients with unresectable HCC treated with pembrolizumab.METHODS From March 2019 to February 2021,a total of 190 unresectable HCC(Barcelona Clinic Liver Cancer C)patients receiving pembrolizumab treatment were retrospectively reviewed.Overall survival(OS)was the primary endpoint,while objective response rate(ORR),disease control rate(DCR),and time to progression(TTP)were secondary evaluation indexes.We assessed demographics,irAEs,and outcomes by retrospective review.RESULTS One hundred and forty-three males and 47 females were included in the study.The ORR and DCR were 12.1%(23/190)and 52.1%(99/190),respectively.The median OS was 376 d[95%confidence interval(CI):340-411 d]and the median TTP was 98 d(95%CI:75-124 d).The overall incidence of treatment-related adverse events was 72.6%(138/190)and 10.0%of them were severe irAEs(grade≥3).Child-Pugh B class,portal vein tumor thrombus,extrahepatic metastasis,and hypothyroidism were the independent risk factors for survival.Patients with hypothyroidism showed a longer OS[517 d(95%CI:423-562)vs 431 d(95%CI:412-485),P=0.011]and TTP[125 d(95%CI:89-154)vs 87 d(95%CI:61-98),P=0.004]than those without irAEs.CONCLUSION Pembrolizumab-treated patients with unresectable HCC who experienced hypothyroidism have promising ORR and durable response.Hypothyroidism,an irAE,may be used as a clinical evaluation parameter of response to ICIs in unresectable HCC.展开更多
Lymphoma,which is highly malignant,stems from lymph nodes and lymphoid tissue.Lymphoma cells express programmed death-ligand 1/2(PD-L1/PD-L2),which binds with programmed cell death 1 protein(PD-1)to establish inhibito...Lymphoma,which is highly malignant,stems from lymph nodes and lymphoid tissue.Lymphoma cells express programmed death-ligand 1/2(PD-L1/PD-L2),which binds with programmed cell death 1 protein(PD-1)to establish inhibitory signaling that impedes the normal function of T cells and allows tumor cells to escape immune system surveillance.Recently,immune checkpoint inhibitor immunotherapies such as PD-1 inhibitors(nivolumab and pembrolizumab)have been introduced into the lymphoma treatment algorithm and have shown remarkable clinical efficacy and greatly improve prognosis in lymphoma patients.Accordingly,the number of lymphoma patients who are seeking treatment with PD-1 inhibitors is growing annually,which results in an increasing number of patients developing immune-related adverse events(irAEs).The occurrence of irAEs inevitably affects the benefits provided by immunotherapy,particularly when PD-1 inhibitors are applied.However,the mechanisms and characteristics of irAEs induced by PD-1 inhibitors in lymphoma need further investigation.This review article summarizes the latest research advances in irAEs during treatment of lymphoma with PD-1 inhibitors.A comprehensive understanding of irAEs incurred in immunotherapy can help to achieve better efficacy with PD-1 inhibitors in lymphoma.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 Gastric cancer(GC)is the most commonly diagnosed malignancy worldwide.Increasing evidence suggests that it is necessary to further explore genetic and immunological characteristics of GC.AIM To construct an...BACKGROUND Gastric cancer(GC)is the most commonly diagnosed malignancy worldwide.Increasing evidence suggests that it is necessary to further explore genetic and immunological characteristics of GC.AIM To construct an immune-related gene(IRG)signature for accurately predicting the prognosis of patients with GC.METHODS Differentially expressed genes(DEGs)between 375 gastric cancer tissues and 32 normal adjacent tissues were obtained from The Cancer Genome Atlas(TCGA)GDC data portal.Then,differentially expressed IRGs from the ImmPort database were identified for GC.Cox univariate survival analysis was used to screen survival-related IRGs.Differentially expressed survival-related IRGs were considered as hub IRGs.Genetic mutations of hub IRGs were analyzed.Then,hub IRGs were selected to conduct a prognostic signature.Receiver operating characteristic(ROC)curve analysis was used to evaluate the prognostic performance of the signature.The correlation of the signature with clinical features and tumor-infiltrating immune cells was analyzed.RESULTS Among all DEGs,70 hub IRGs were obtained for GC.The deletions and amplifications were the two most common types of genetic mutations of hub IRGs.A prognostic signature was identified,consisting of ten hub IRGs(including S100A12,DEFB126,KAL1,APOH,CGB5,GRP,GLP2R,LGR6,PTGER3,and CTLA4).This prognostic signature could accurately distinguish patients into highand low-risk groups,and overall survival analysis showed that high risk patients had shortened survival time than low risk patients(P<0.0001).The area under curve of the ROC of the signature was 0.761,suggesting that the prognostic signature had a high sensitivity and accuracy.Multivariate regression analysis demonstrated that the prognostic signature could become an independent prognostic predictor for GC after adjustment for other clinical features.Furthermore,we found that the prognostic signature was significantly correlated with macrophage infiltration.CONCLUSION Our study proposed an immune-related prognostic signature for GC,which could help develop treatment strategies for patients with GC in the future.展开更多
Objective To observe the expression of inlfammatory molecules in bone marrow immune cells of patients with immune-related hematocytopenia (IRH), and to investigate the immune mechanism and clinical signiifcance of the...Objective To observe the expression of inlfammatory molecules in bone marrow immune cells of patients with immune-related hematocytopenia (IRH), and to investigate the immune mechanism and clinical signiifcance of the disease. Methods Total of 36 IRH patients were selected as observation group and 30 healthy people were taken as control group. Serum cytokines levels, activity of immunocytes and expression of HLA-DR were detected. Immune lfuorescence was applied to observe the expression state of immunologic molecules and cytokines in IRH patients. Results Serum cytokines were elevated in various degrees in observation group. Compared with the control group, the cytokines levels were significantly higher (P < 0.05). After treatement with immunosuppressive drugs, the serum levels of cytokines in observation group reduced to a level close to the control group. HLA-DR were upregulated in activated tissue basophils, eosinophils, dendritic cells (DC) and macrophages of bone marrow in IRH patients, and POX activity in these immunocytes of IRH was higher than that of the control group. Immune molecules were highly expressed in eosinophils, DC and macrophages. Conclusions It is demonstrated that antibodies or self-reactive lymphocytes were produced in IRH marrow, which would cause lesions of hemocytes, and lead to pathological process ifnally. Structure of hematopoietic cells mutated and these cells might be acted as target cells of immunocytes in the pathological process. Immunocytes could secrete inlfammatory factors and lead to immunologic injury of hemocyte.展开更多
Immune checkpoint inhibitors(ICPI)have shown considerable promise in the treatment of tumors.However,immune-related adverse events(irAEs)caused by ICPI have been reported in nearly every organ system.Whilst this repre...Immune checkpoint inhibitors(ICPI)have shown considerable promise in the treatment of tumors.However,immune-related adverse events(irAEs)caused by ICPI have been reported in nearly every organ system.Whilst this represents a new challenge in the field of cancer treatment,traditional Chinese medicine(TCM)provides benefits in the treatment of irAEs.This article reviews the studies of the treatment of immune-related gastrointestinal diseases and dermatosis with TCM and introduces the collaborative efforts between China and France in the implementation of TCM for the treatment of irAEs.展开更多
AIM:To construct an immune-related prognostic signature(IPS)that can distinguish and predict prognosis in uveal melanoma(UM).METHODS:The transcriptomic data and clinicopathological information of 80 UM patients were e...AIM:To construct an immune-related prognostic signature(IPS)that can distinguish and predict prognosis in uveal melanoma(UM).METHODS:The transcriptomic data and clinicopathological information of 80 UM patients were extracted from the TCGA database.These patients were randomly assigned to a training and a testing set.RESULTS:Lasso Cox analysis was performed for the prognostic immune-related genes to develop an IPS for UM in the training set.The signature was validated in both the testing set and entire cohort.We confirmed the prognostic value of our IPS in distinct subgroups and found its association with the T stage and basal diameter of the tumor.Tumor Immune Estimation Resource database analysis revealed that the IPS was negatively correlated with the infiltration of neutrophils and dendritic cells,but positively correlated with the infiltration level of CD8+T cells.In addition,we demonstrated that immune checkpoints containing PD-1,CTLA-4,IDO,and TIGIT were moderately associated with the IPS.CONCLUSION:This is the first study to develop and validate an immune-related signature with the ability of predicting prognosis for UM patients.Further studies are needed to validate its prediction accuracy.展开更多
Breast cancer is one of the most common cancers in the world and seriously threatens the health of women worldwide.Prognostic models based on immune-related genes help to improve the prognosis prediction and clinical ...Breast cancer is one of the most common cancers in the world and seriously threatens the health of women worldwide.Prognostic models based on immune-related genes help to improve the prognosis prediction and clinical treatment of breast cancer patients.In the study,we used weighted gene co-expression network analysis to construct a co-expression network to screen out highly prognostic immune-related genes.Subsequently,the prognostic immunerelated gene signature was successfully constructed from highly immune-related genes through COX regression and LASSO COX analysis.Survival analysis and time receiver operating characteristic curves indicate that the prognostic signature has strong predictive performance.And we developed a nomogram by combing the risk score with multiple clinical characteristics.CIBERSORT and TIMER algorithms confirmed that there are significant differences in tumorinfiltrating immune cells in different risk groups.In addition,gene set enrichment analysis shows 6 pathways that differ between high-and low-risk group.The immune-related gene signature effectively predicts the survival and immune infiltration of breast cancer patients and is expected to provide more effective immunotherapy targets for the prognosis prediction of breast cancer.展开更多
BACKGROUND Secondary sclerosing cholangitis,characterized by biliary obstruction,can be caused by drugs such as immune checkpoint inhibitors(ICIs).While there a few reports of sclerosing cholangitis after immune check...BACKGROUND Secondary sclerosing cholangitis,characterized by biliary obstruction,can be caused by drugs such as immune checkpoint inhibitors(ICIs).While there a few reports of sclerosing cholangitis after immune checkpoint inhibitor administration,no case has been reported after discontinuation of such drugs.CASE SUMMARY A 68-year-old man who underwent chemotherapy for lung adenocarcinoma with bone metastasis presented with abdominal pain and fever 4 mo after the final administration of pembrolizumab.Computed tomography revealed thickening of the gallbladder wall and dilatation of the common bile duct.Endoscopic retrograde cholangiopancreatography revealed an irregularly narrowed intrahepatic bile duct.Biopsy of the bile duct demonstrated that CD8+T cells were predominant over CD4+T cells.Liver biopsy showed dominant infiltration of CD8+T in the portal tract,but onion-skin lesions were not observed.The patient was diagnosed with immune-related sclerosing cholangitis induced by pembrolizumab.Administration of methylprednisolone and endoscopic nasobiliary drainage were performed,but the cholangiography and laboratory test findings did not improve.No further treatment was administered due to disease progression,and the patient was referred for palliative care.CONCLUSION Immune-related sclerosing cholangitis may have a late onset,and such cases occurring after discontinuation of ICIs should be carefully managed.展开更多
Objective: To construct an Immune-Related Gene Prognostic Index (IRGPI) for bladder cancer using a bioanalytical approach to analyze its molecular and immunological characteristics, as well as to assess the benefit of...Objective: To construct an Immune-Related Gene Prognostic Index (IRGPI) for bladder cancer using a bioanalytical approach to analyze its molecular and immunological characteristics, as well as to assess the benefit of Immune Checkpoint Inhibitor (ICI) therapy in the IRGPI-defined bladder cancer subgroup. Methods: Twenty-nine immune-related pivotal genes were identified by Weighted Gene Co-expression Network Analysis (WGCNA) based on The Cancer Genome Atlas (TCGA) bladder cancer immune dataset (n = 433). Six genes were identified using a multifactorial Cox regression approach to construct the IRGPI and validated against the Gene Expression Omnibus (GEO) dataset (n = 256). Then, molecular and immunological features in the subgroups defined by IRGPI were synthesized by GSEA, Kaplan-Meier survival curves, and other methods, and the benefit of ICI treatment was assessed. Results: IRGPI was constructed based on six genes including AHNAK, ILK, OGN, PDGFD, PPARGC1B, and JAM3. Patients with low IRGPI had better Overall Survival (OS) than those with high IRGPI, which was confirmed in the validation cohort of GEO. Pooled analysis showed that the low IRGPI subgroup was associated with higher infiltration of CD8 T cells, activated memory CD4 T cells, and could benefit from ICI treatment. Meanwhile, high IRGPI subgroups were associated with higher resting memory CD4T cells, M0 macrophages, and M2 macrophage content, immunosuppression, and benefited less from ICI treatment. Conclusion: IRGPI is a novel biomarker with better efficacy in differentiating the prognosis of bladder cancer, molecular and immune features, and evaluation of ICI therapy for individualized treatment of bladder cancer.展开更多
Objective This study aimed to construct a prognostic model for rectal adenocarcinomas based on immune-related long noncoding RNAs(lncRNAs)and verify its prediction efficiency.Methods Transcript data and clinical data ...Objective This study aimed to construct a prognostic model for rectal adenocarcinomas based on immune-related long noncoding RNAs(lncRNAs)and verify its prediction efficiency.Methods Transcript data and clinical data of rectal adenocarcinomas were downloaded from The Cancer Genome Atlas(TCGA)database.Perl software(strawberry version)and R language(version 3.6.1)were used to analyze the immune-related genes and immune-related lncRNAs of rectal adenocarcinomas,and the differentially expressed immune-related lncRNAs were screened according to the criteria|log2FC|>1 and P<0.05.The key immune-related lncRNAs were screened using single-factor Cox regression analysis and lasso regression analysis.Multivariate Cox regression analysis was performed to construct an immune-related lncRNA prognostic model using the risk scores.Next,we evaluated the effectiveness of the model through Kaplan-Meier(K-M)survival analysis,ROC curve analysis,and independent prognostic analysis of clinical features.In addition,prognostic biomarkers of immune-related lncRNAs in the model were analyzed by K-M survival analysis.Results In this study,we obtained gene expression profile matrices of 89 rectal adenocarcinomas and 2 paracancerous specimens from TCGA database and applied immunologic signatures to these transcripts.Through R and Perl software analysis,we obtained 847 immune-related lncRNAs and 331 protein-encoded immune-related genes in rectal adenocarcinomas.Eight important immune-related lncRNAs related to the prognosis of rectal adenocarcinomas were identified using univariate Cox regression and lasso regression analysis.Furthermore,four immune-related lncRNAs were identified as prognostic markers of rectal adenocarcinomas via multivariate Cox regression analysis.The prognostic risk model was as follows:risk score=(-4.084)*expression LINC01871+(3.112)*expression AL158152.2+(7.616)*expression PXN-AS1+(-0.867)*expression HCP5.The independent prognostic effect of the rectal adenocarcinoma risk score model was revealed through K-M analysis,ROC curve analysis,and univariate,and multivariate Cox regression analysis(P=0.035).LINC01871(P=0.006),PXN-AS1(P=0.008),and AL158152.2(P=0.0386)were closely correlated with the prognosis of rectal adenocarcinomas through the K-M survival analysis.Conclusion We constructed a prognostic model of rectal adenocarcinomas based on four immune-related lncRNAs by analyzing the data based on TCGA database,with high prediction accuracy.We also identified two biomarkers with poor prognosis(PXN-AS1 and AL158152.2)and one biomarker with good prognosis(LINC01871).展开更多
Objective The aim of this study was to construct a prognostic model of esophageal adenocarcinoma(EAC)based on immune-related long noncoding RNAs(immune-related lncRNAs)and identify prognostic biomarkers using the Canc...Objective The aim of this study was to construct a prognostic model of esophageal adenocarcinoma(EAC)based on immune-related long noncoding RNAs(immune-related lncRNAs)and identify prognostic biomarkers using the Cancer Genome Atlas(TCGA)database.Methods Whole genomic mRNA expression and clinical data of esophageal adenocarcinoma were obtained from the TCGA database.The software Strawberry Perl,R and R packets were used to identify the immune-related genes and lncRNAs of esophageal adenocarcinoma,and for data processing and analysis.The differentially expressed lncRNAs were detected while comparing esophageal adenocarcinoma and normal tissue samples.The key immune-related lncRNAs were screened using lasso regression analysis and univariate cox regression analysis,and used to construct the prognostic model using multivariate cox regression analysis.To evaluate the accuracy of the risk prognostic model,all esophageal adenocarcinomas were divided into high-risk and low-risk groups according to the median risk score,after which Kaplan-Meier(K-M)survival curves,operating characteristic(ROC)curve and independent prognostic analysis of clinical traits were created.In addition,statistically significant immune-related lncRNAs and potential prognostic biomarkers were identified using the prognostic model and multifactor cox regression analysis for k-m survival analysis.Results A total of 1322 differentially expressed immune-related lncRNAs were identified,28 of which were associated with prognosis via univariate cox regression analysis.In addition,K-M survival analysis showed that the total survival time of the higher risk group was significantly shorter than that of the lower risk group(P=1.063e-10).The area under the ROC curve of 5-year total survival rate was 0.90.The risk score showed independent prognostic risk for esophageal adenocarcinoma via single factor and multifactorial independent prognostic analyses.In addition,the HR and 95%CI of each key immune-related lncRNA were calculated using multivariate Cox regression.Using k-m survival analysis,we found that 5 out of 12 key significant immune-related lncRNAs had independent prognostic value[AL136115.1(P=0.006),AC079684.1(P=0.008),AC07916394.1(P=0.0386),AC087620.1(P=0.041)and MIRLET7BHG(P=0.044)].Conclusion The present study successfully constructed a prognostic model of esophageal adenocarcinoma based on the TCGA database,with moderate predictive accuracy.The model consisted of the expression level of 12 immune-related lncRNAs.Furthermore,the study identified one favorable prognostic biomarker,MIRLET7BHG,and four poor prognostic biomarkers(AL136115.1,AC079684.1,AC016394.1,and AC087620.1).展开更多
With the wide application of immunotherapy drug PD-1/PD-L1 inhibitor in China and the continuous clinical research,a major problem that we have to face is the immune-related pneumonia caused by PD-1/PD-L1.At present,w...With the wide application of immunotherapy drug PD-1/PD-L1 inhibitor in China and the continuous clinical research,a major problem that we have to face is the immune-related pneumonia caused by PD-1/PD-L1.At present,western medicine mainly treated it by hormone therapy,which may cause side effects,such as obesity,osteoporosis and osteonecrosis for hormone therapy by long-term,and increase the patients'pain.Under the guidance of the theory of syndrome differentiation,traditional Chinese medicine(TCM)advocates the methods of expelling wind and clearing away cold,resolving phlegm and relieving asthma,relieving heat from lung,and invigorating the spleen and tonifying the kidney,etc.Exact differentiation of symptoms and rational usage of drugs can play an important role in the early prevention and treatment of immune-related pneumonia,reflecting the important role of TCM in the prevention and treatment of side effects of new drugs.In order to provide an effective clinical reference for clinicians in the practice of using PD-1/PD-L1,this paper systematically reviewed the use of TCM in the treatment of immune-related pneumonia induced by PD-1/PD-L1 inhibitors.展开更多
基金Beijing CSCO Clinical Oncology Research Foundation,No.Y-HH202102-0308.
文摘BACKGROUND Treatment options for patients with gastric cancer(GC)continue to improve,but the overall prognosis is poor.The use of PD-1 inhibitors has also brought benefits to patients with advanced GC and has gradually become the new standard treatment option at present,and there is an urgent need to identify valuable biomarkers to classify patients with different characteristics into subgroups.AIM To determined the effects of differentially expressed immune-related genes(DEIRGs)on the development,prognosis,tumor microenvironment(TME),and treatment response among GC patients with the expectation of providing new biomarkers for personalized treatment of GC populations.METHODS Gene expression data and clinical pathologic information were downloaded from The Cancer Genome Atlas(TCGA),and immune-related genes(IRGs)were searched from ImmPort.DEIRGs were extracted from the intersection of the differentially-expressed genes(DEGs)and IRGs lists.The enrichment pathways of key genes were obtained by analyzing the Kyoto Encyclopedia of Genes and Genomes(KEGGs)and Gene Ontology(GO)databases.To identify genes associated with prognosis,a tumor risk score model based on DEIRGs was constructed using Least Absolute Shrinkage and Selection Operator and multivariate Cox regression.The tumor risk score was divided into high-and lowrisk groups.The entire cohort was randomly divided into a 2:1 training cohort and a test cohort for internal validation to assess the feasibility of the risk model.The infiltration of immune cells was obtained using‘CIBERSORT,’and the infiltration of immune subgroups in high-and low-risk groups was analyzed.The GC immune score data were obtained and the difference in immune scores between the two groups was analyzed.RESULTS We collected 412 GC and 36 adjacent tissue samples,and identified 3627 DEGs and 1311 IRGs.A total of 482 DEIRGs were obtained.GO analysis showed that DEIRGs were mainly distributed in immunoglobulin complexes,receptor ligand activity,and signaling receptor activators.KEGG pathway analysis showed that the top three DEIRGs enrichment types were cytokine-cytokine receptors,neuroactive ligand receptor interactions,and viral protein interactions.We ultimately obtained an immune-related signature based on 10 genes,including 9 risk genes(LCN1,LEAP2,TMSB15A mRNA,DEFB126,PI15,IGHD3-16,IGLV3-22,CGB5,and GLP2R)and 1 protective gene(LGR6).Kaplan-Meier survival analysis,receiver operating characteristic curve analysis,and risk curves confirmed that the risk model had good predictive ability.Multivariate COX analysis showed that age,stage,and risk score were independent prognostic factors for patients with GC.Meanwhile,patients in the low-risk group had higher tumor mutation burden and immunophenotype,which can be used to predict the immune checkpoint inhibitor response.Both cytotoxic T lymphocyte antigen4+and programmed death 1+patients with lower risk scores were more sensitive to immunotherapy.CONCLUSION In this study a new prognostic model consisting of 10 DEIRGs was constructed based on the TME.By providing risk factor analysis and prognostic information,our risk model can provide new directions for immunotherapy in GC patients.
基金supported by the General Program of the National Natural Science Foundation of China (Grant No. 82073376)。
文摘Pseudomyxoma peritonei(PMP) is an indolent malignant syndrome. The standard treatment for PMP is cytoreductive surgery combined with intraperitoneal hyperthermic chemotherapy(CRS + HIPEC). However, the high recurrence rate and latent clinical symptoms and signs are major obstacles to further improving clinical outcomes. Moreover, patients in advanced stages receive little benefit from CRS + HIPEC due to widespread intraperitoneal metastases. Another challenge in PMP treatment involves the progressive sclerosis of PMP cell-secreted mucus, which is often increased due to activating mutations in the gene coding for guanine nucleotide-binding protein alpha subunit(GNAS). Consequently, the development of other PMP therapies is urgently needed. Several immune-related therapies have shown promise, including the use of bacterium-derived non-specific immunogenic agents, radioimmunotherapeutic agents, and tumor cell-derived neoantigens, but a well-recognized immunotherapy has not been established. In this review the roles of GNAS mutations in the promotion of mucin secretion and disease development are discussed. In addition, the immunologic features of the PMP microenvironment and immune-associated treatments are discussed to summarize the current understanding of key features of the disease and to facilitate the development of immunotherapies.
文摘Gastric cancer ranks as the sixth most prevalent cancer worldwide.In recent research within the realm of gastric cancer treatment,the identification and application of immune-related genetic features have emerged as groundbreaking advancements.The study by Ma et al,which developed a prognostic model based on 10 genes,categorizes patients into high and low-risk groups to predict their responsiveness to immune checkpoint inhibitor therapy.This research underscores the potential of immune-related genes as biomarkers for personalized treatment,offering insights into tumor mutation burden and immune phenotype scores.We advocate for further validation,understanding of biological mechanisms,and integration of diverse datasets to enhance the model's predictive accuracy and clinical application,marking a significant step towards personalized and precise treatment for gastric cancer.
文摘We conducted a comprehensive review of existing prediction models pertaining to the efficacy of immune-checkpoint inhibitor(ICI)and the occurrence of immune-related adverse events(irAEs).The predictive potential of neutrophil-to-lymphocyte ratio(NLR)and platelet-to-lymphocyte ratio(PLR)in determining ICI effectiveness has been extensively investigated,while limited research has been conducted on predicting irAEs.Furthermore,the combined model incor-porating NLR and PLR,either with each other or in conjunction with additional markers such as carcinoembryonic antigen,exhibits superior predictive capabilities compared to individual markers alone.NLR and PLR are promising markers for clinical applications.Forthcoming models ought to incorporate established efficacious models and newly identified ones,thereby constituting a multifactor composite model.Furthermore,efforts should be made to explore effective clinical application approaches that enhance the predictive accuracy and efficiency.
基金Supported by The Fundamental Research Funds for the Central Universities,No.2019CDYGYB024The National Natural Science Foundation of China,No.31300726The Chongqing Primary and Middle School Innovation Talent Training Project,No.CY220113.
文摘Immune checkpoint inhibitors(ICIs)constitute a pivotal class of immunotherapeutic drugs in cancer treatment.However,their widespread clinical application has led to a notable surge in immune-related adverse events(irAEs),significantly affecting the efficacy and survival rates of patients undergoing ICI therapy.While conventional hematological and imaging tests are adept at detecting organ-specific toxicities,distinguishing adverse reactions from those induced by viruses,bacteria,or immune diseases remains a formidable challenge.Consequently,there exists an urgent imperative for reliable biomarkers capable of accurately predicting or diagnosing irAEs.Thus,a thorough review of existing studies on irAEs biomarkers is indispensable.Our review commences by providing a succinct over-view of major irAEs,followed by a comprehensive summary of irAEs biomarkers across various dimensions.Furthermore,we delve into innovative methodologies such as machine learning,single-cell RNA sequencing,multiomics analysis,and gut microbiota profiling to identify novel,robust biomarkers that can facilitate precise irAEs diagnosis or prediction.Lastly,this review furnishes a concise exposition of irAEs mechanisms to augment understanding of irAEs prediction,diagnosis,and treatment strategies.
文摘Purpose research on nursing sensitive indicators in tumor Patients application effect in immune-related skin toxicity management. Method select our hospital April to June, 202360 cases patients with immune therapy settings as the control group. August-October, 2023 60 cases the patients treated with immune therapy were the experimental group. The control group adopted regular nursing methods, while the experimental group sensitive Indicators, evidence-based give preventive care. The social situation, psychological state, physical function, quality of life score, incidence of skin toxicity caused by immune checkpoint inhibitors, moderate and above of the two groups of patients were compared. Incidence of skin toxicity. Result: experience group SAS score, SDS score higher than the control group, the difference was statistically significant (P < 0.05);The incidence of skin toxic reactions caused by immune checkpoint inhibitors and the incidence of moderate and above skin toxic reactions in the experimental group are lower than those in the control group, and the difference is statistically significant (P < 0.05). Conclusion: sensitive indicator guidance evidence-based preventive care can reduce the degree of immune-related skin toxicity, improve the psychological state and quality of life of tumor patients treated with immune therapy and reduce the incidence of adverse reactions, improve nursing quality and patient satisfaction.
基金supported by the Shenyang City-School Joint Funding Project (No.2400022093).
文摘Background:Hepatocellular carcinoma(HCC)appears to be strongly associated with immune-related genes.However,immune-related genes are not well understood as a prognostic marker in HCC caused by the hepatitis B virus(HBV).The purpose of this study was to investigate the prognostic significance of immune-related genes in HBV-infected HCC.Methods:Gene expression data from 114 HBV-infected HCC and 50 normal tissues were integrated into The Cancer Genome Atlas.Differentially expressed immune-associated genes were analyzed to identify immune-associated differential genes associated with overall survival.Least Absolute Shrinkage and Selection Operator and multivariate Cox regressions were used to constructing immunoprognostic models.An independent prognostic factor analysis using multiple Cox regressions was also performed for HBV-infected HCCs.Immunocorrelation analysis markers and immune cell infiltration were also investigated.Results:We found 113 differentially expressed immune-associated genes.Immune-related differential genes were significantly correlated with the overall survival of HCC patients.We constructed an immune-based prognostic model using multivariate Cox regression analysis including seven immune-related genes.According to further analysis,immune-related prognostic factors may serve as independent prognostic indicators in the clinical setting.There is also evidence that the 7-gene prognostic model reflects the tumor immune microenvironment as a result of the risk score model and immune cell infiltration.Conclusions:As a result of our study,we screened immune-related genes for prognosis in HBV-infected HCC and developed a novel immune-based prognostic model.The research not only provides new prognostic biomarkers but also offers insight into the tumor immune microenvironment and lays the theoretical groundwork for immunotherapy.
文摘BACKGROUND Although immune checkpoint inhibitor(ICI)therapy has improved the prognosis of unresectable hepatocellular carcinoma(HCC),it has also resulted in unique immune-related adverse events(irAEs).The relationship between irAE and treatment outcomes in ICI-treated unresectable HCC patients remains unknown.AIM To elucidate the correlation between immune-related toxic effects and prognosis in patients with unresectable HCC treated with pembrolizumab.METHODS From March 2019 to February 2021,a total of 190 unresectable HCC(Barcelona Clinic Liver Cancer C)patients receiving pembrolizumab treatment were retrospectively reviewed.Overall survival(OS)was the primary endpoint,while objective response rate(ORR),disease control rate(DCR),and time to progression(TTP)were secondary evaluation indexes.We assessed demographics,irAEs,and outcomes by retrospective review.RESULTS One hundred and forty-three males and 47 females were included in the study.The ORR and DCR were 12.1%(23/190)and 52.1%(99/190),respectively.The median OS was 376 d[95%confidence interval(CI):340-411 d]and the median TTP was 98 d(95%CI:75-124 d).The overall incidence of treatment-related adverse events was 72.6%(138/190)and 10.0%of them were severe irAEs(grade≥3).Child-Pugh B class,portal vein tumor thrombus,extrahepatic metastasis,and hypothyroidism were the independent risk factors for survival.Patients with hypothyroidism showed a longer OS[517 d(95%CI:423-562)vs 431 d(95%CI:412-485),P=0.011]and TTP[125 d(95%CI:89-154)vs 87 d(95%CI:61-98),P=0.004]than those without irAEs.CONCLUSION Pembrolizumab-treated patients with unresectable HCC who experienced hypothyroidism have promising ORR and durable response.Hypothyroidism,an irAE,may be used as a clinical evaluation parameter of response to ICIs in unresectable HCC.
基金the 2022 Project of Innovation Foundation of Outstanding Graduate Students of Gansu Provincethe Graduate Innovation Foundation of Major Project of Education Department of Gansu Province,No.lccx2021001+2 种基金the Gansu Provincial Science and Technology Plan Project Assignment(Innovation Base and Talent Plan),No.21JR7RA013the Gansu Province Innovation Base and Talent Plan(Gansu Province Leukemia Clinical Research Center),No.21JR7RA015the 2022 Hospital Project of The 940th Hospital of Joint Logistics Support Force of Chinese People's Liberation Army,No.2022yxky015.
文摘Lymphoma,which is highly malignant,stems from lymph nodes and lymphoid tissue.Lymphoma cells express programmed death-ligand 1/2(PD-L1/PD-L2),which binds with programmed cell death 1 protein(PD-1)to establish inhibitory signaling that impedes the normal function of T cells and allows tumor cells to escape immune system surveillance.Recently,immune checkpoint inhibitor immunotherapies such as PD-1 inhibitors(nivolumab and pembrolizumab)have been introduced into the lymphoma treatment algorithm and have shown remarkable clinical efficacy and greatly improve prognosis in lymphoma patients.Accordingly,the number of lymphoma patients who are seeking treatment with PD-1 inhibitors is growing annually,which results in an increasing number of patients developing immune-related adverse events(irAEs).The occurrence of irAEs inevitably affects the benefits provided by immunotherapy,particularly when PD-1 inhibitors are applied.However,the mechanisms and characteristics of irAEs induced by PD-1 inhibitors in lymphoma need further investigation.This review article summarizes the latest research advances in irAEs during treatment of lymphoma with PD-1 inhibitors.A comprehensive understanding of irAEs incurred in immunotherapy can help to achieve better efficacy with PD-1 inhibitors in lymphoma.
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.
文摘BACKGROUND Gastric cancer(GC)is the most commonly diagnosed malignancy worldwide.Increasing evidence suggests that it is necessary to further explore genetic and immunological characteristics of GC.AIM To construct an immune-related gene(IRG)signature for accurately predicting the prognosis of patients with GC.METHODS Differentially expressed genes(DEGs)between 375 gastric cancer tissues and 32 normal adjacent tissues were obtained from The Cancer Genome Atlas(TCGA)GDC data portal.Then,differentially expressed IRGs from the ImmPort database were identified for GC.Cox univariate survival analysis was used to screen survival-related IRGs.Differentially expressed survival-related IRGs were considered as hub IRGs.Genetic mutations of hub IRGs were analyzed.Then,hub IRGs were selected to conduct a prognostic signature.Receiver operating characteristic(ROC)curve analysis was used to evaluate the prognostic performance of the signature.The correlation of the signature with clinical features and tumor-infiltrating immune cells was analyzed.RESULTS Among all DEGs,70 hub IRGs were obtained for GC.The deletions and amplifications were the two most common types of genetic mutations of hub IRGs.A prognostic signature was identified,consisting of ten hub IRGs(including S100A12,DEFB126,KAL1,APOH,CGB5,GRP,GLP2R,LGR6,PTGER3,and CTLA4).This prognostic signature could accurately distinguish patients into highand low-risk groups,and overall survival analysis showed that high risk patients had shortened survival time than low risk patients(P<0.0001).The area under curve of the ROC of the signature was 0.761,suggesting that the prognostic signature had a high sensitivity and accuracy.Multivariate regression analysis demonstrated that the prognostic signature could become an independent prognostic predictor for GC after adjustment for other clinical features.Furthermore,we found that the prognostic signature was significantly correlated with macrophage infiltration.CONCLUSION Our study proposed an immune-related prognostic signature for GC,which could help develop treatment strategies for patients with GC in the future.
文摘Objective To observe the expression of inlfammatory molecules in bone marrow immune cells of patients with immune-related hematocytopenia (IRH), and to investigate the immune mechanism and clinical signiifcance of the disease. Methods Total of 36 IRH patients were selected as observation group and 30 healthy people were taken as control group. Serum cytokines levels, activity of immunocytes and expression of HLA-DR were detected. Immune lfuorescence was applied to observe the expression state of immunologic molecules and cytokines in IRH patients. Results Serum cytokines were elevated in various degrees in observation group. Compared with the control group, the cytokines levels were significantly higher (P < 0.05). After treatement with immunosuppressive drugs, the serum levels of cytokines in observation group reduced to a level close to the control group. HLA-DR were upregulated in activated tissue basophils, eosinophils, dendritic cells (DC) and macrophages of bone marrow in IRH patients, and POX activity in these immunocytes of IRH was higher than that of the control group. Immune molecules were highly expressed in eosinophils, DC and macrophages. Conclusions It is demonstrated that antibodies or self-reactive lymphocytes were produced in IRH marrow, which would cause lesions of hemocytes, and lead to pathological process ifnally. Structure of hematopoietic cells mutated and these cells might be acted as target cells of immunocytes in the pathological process. Immunocytes could secrete inlfammatory factors and lead to immunologic injury of hemocyte.
基金funded by the National Natural Science Foundation of China:Surface Project(81573959)the Young Teacher Research Program of the Beijing University of Chinese Medicine(2017-JYB-JS-158)Young Scientist Program of the Dongzhimen Hospital,Beijing University of Chinese Medicine(DZMYS-201610).
文摘Immune checkpoint inhibitors(ICPI)have shown considerable promise in the treatment of tumors.However,immune-related adverse events(irAEs)caused by ICPI have been reported in nearly every organ system.Whilst this represents a new challenge in the field of cancer treatment,traditional Chinese medicine(TCM)provides benefits in the treatment of irAEs.This article reviews the studies of the treatment of immune-related gastrointestinal diseases and dermatosis with TCM and introduces the collaborative efforts between China and France in the implementation of TCM for the treatment of irAEs.
文摘AIM:To construct an immune-related prognostic signature(IPS)that can distinguish and predict prognosis in uveal melanoma(UM).METHODS:The transcriptomic data and clinicopathological information of 80 UM patients were extracted from the TCGA database.These patients were randomly assigned to a training and a testing set.RESULTS:Lasso Cox analysis was performed for the prognostic immune-related genes to develop an IPS for UM in the training set.The signature was validated in both the testing set and entire cohort.We confirmed the prognostic value of our IPS in distinct subgroups and found its association with the T stage and basal diameter of the tumor.Tumor Immune Estimation Resource database analysis revealed that the IPS was negatively correlated with the infiltration of neutrophils and dendritic cells,but positively correlated with the infiltration level of CD8+T cells.In addition,we demonstrated that immune checkpoints containing PD-1,CTLA-4,IDO,and TIGIT were moderately associated with the IPS.CONCLUSION:This is the first study to develop and validate an immune-related signature with the ability of predicting prognosis for UM patients.Further studies are needed to validate its prediction accuracy.
基金Science and Technology Innovation Project of Social People’s Livelihood,Yongchuan District,Chongqing(Ycstc,2017cb5502).
文摘Breast cancer is one of the most common cancers in the world and seriously threatens the health of women worldwide.Prognostic models based on immune-related genes help to improve the prognosis prediction and clinical treatment of breast cancer patients.In the study,we used weighted gene co-expression network analysis to construct a co-expression network to screen out highly prognostic immune-related genes.Subsequently,the prognostic immunerelated gene signature was successfully constructed from highly immune-related genes through COX regression and LASSO COX analysis.Survival analysis and time receiver operating characteristic curves indicate that the prognostic signature has strong predictive performance.And we developed a nomogram by combing the risk score with multiple clinical characteristics.CIBERSORT and TIMER algorithms confirmed that there are significant differences in tumorinfiltrating immune cells in different risk groups.In addition,gene set enrichment analysis shows 6 pathways that differ between high-and low-risk group.The immune-related gene signature effectively predicts the survival and immune infiltration of breast cancer patients and is expected to provide more effective immunotherapy targets for the prognosis prediction of breast cancer.
文摘BACKGROUND Secondary sclerosing cholangitis,characterized by biliary obstruction,can be caused by drugs such as immune checkpoint inhibitors(ICIs).While there a few reports of sclerosing cholangitis after immune checkpoint inhibitor administration,no case has been reported after discontinuation of such drugs.CASE SUMMARY A 68-year-old man who underwent chemotherapy for lung adenocarcinoma with bone metastasis presented with abdominal pain and fever 4 mo after the final administration of pembrolizumab.Computed tomography revealed thickening of the gallbladder wall and dilatation of the common bile duct.Endoscopic retrograde cholangiopancreatography revealed an irregularly narrowed intrahepatic bile duct.Biopsy of the bile duct demonstrated that CD8+T cells were predominant over CD4+T cells.Liver biopsy showed dominant infiltration of CD8+T in the portal tract,but onion-skin lesions were not observed.The patient was diagnosed with immune-related sclerosing cholangitis induced by pembrolizumab.Administration of methylprednisolone and endoscopic nasobiliary drainage were performed,but the cholangiography and laboratory test findings did not improve.No further treatment was administered due to disease progression,and the patient was referred for palliative care.CONCLUSION Immune-related sclerosing cholangitis may have a late onset,and such cases occurring after discontinuation of ICIs should be carefully managed.
文摘Objective: To construct an Immune-Related Gene Prognostic Index (IRGPI) for bladder cancer using a bioanalytical approach to analyze its molecular and immunological characteristics, as well as to assess the benefit of Immune Checkpoint Inhibitor (ICI) therapy in the IRGPI-defined bladder cancer subgroup. Methods: Twenty-nine immune-related pivotal genes were identified by Weighted Gene Co-expression Network Analysis (WGCNA) based on The Cancer Genome Atlas (TCGA) bladder cancer immune dataset (n = 433). Six genes were identified using a multifactorial Cox regression approach to construct the IRGPI and validated against the Gene Expression Omnibus (GEO) dataset (n = 256). Then, molecular and immunological features in the subgroups defined by IRGPI were synthesized by GSEA, Kaplan-Meier survival curves, and other methods, and the benefit of ICI treatment was assessed. Results: IRGPI was constructed based on six genes including AHNAK, ILK, OGN, PDGFD, PPARGC1B, and JAM3. Patients with low IRGPI had better Overall Survival (OS) than those with high IRGPI, which was confirmed in the validation cohort of GEO. Pooled analysis showed that the low IRGPI subgroup was associated with higher infiltration of CD8 T cells, activated memory CD4 T cells, and could benefit from ICI treatment. Meanwhile, high IRGPI subgroups were associated with higher resting memory CD4T cells, M0 macrophages, and M2 macrophage content, immunosuppression, and benefited less from ICI treatment. Conclusion: IRGPI is a novel biomarker with better efficacy in differentiating the prognosis of bladder cancer, molecular and immune features, and evaluation of ICI therapy for individualized treatment of bladder cancer.
基金Supported by a grant from the Health Commission of Hubei Province Scientific Research Project(No.WJ2019M118)。
文摘Objective This study aimed to construct a prognostic model for rectal adenocarcinomas based on immune-related long noncoding RNAs(lncRNAs)and verify its prediction efficiency.Methods Transcript data and clinical data of rectal adenocarcinomas were downloaded from The Cancer Genome Atlas(TCGA)database.Perl software(strawberry version)and R language(version 3.6.1)were used to analyze the immune-related genes and immune-related lncRNAs of rectal adenocarcinomas,and the differentially expressed immune-related lncRNAs were screened according to the criteria|log2FC|>1 and P<0.05.The key immune-related lncRNAs were screened using single-factor Cox regression analysis and lasso regression analysis.Multivariate Cox regression analysis was performed to construct an immune-related lncRNA prognostic model using the risk scores.Next,we evaluated the effectiveness of the model through Kaplan-Meier(K-M)survival analysis,ROC curve analysis,and independent prognostic analysis of clinical features.In addition,prognostic biomarkers of immune-related lncRNAs in the model were analyzed by K-M survival analysis.Results In this study,we obtained gene expression profile matrices of 89 rectal adenocarcinomas and 2 paracancerous specimens from TCGA database and applied immunologic signatures to these transcripts.Through R and Perl software analysis,we obtained 847 immune-related lncRNAs and 331 protein-encoded immune-related genes in rectal adenocarcinomas.Eight important immune-related lncRNAs related to the prognosis of rectal adenocarcinomas were identified using univariate Cox regression and lasso regression analysis.Furthermore,four immune-related lncRNAs were identified as prognostic markers of rectal adenocarcinomas via multivariate Cox regression analysis.The prognostic risk model was as follows:risk score=(-4.084)*expression LINC01871+(3.112)*expression AL158152.2+(7.616)*expression PXN-AS1+(-0.867)*expression HCP5.The independent prognostic effect of the rectal adenocarcinoma risk score model was revealed through K-M analysis,ROC curve analysis,and univariate,and multivariate Cox regression analysis(P=0.035).LINC01871(P=0.006),PXN-AS1(P=0.008),and AL158152.2(P=0.0386)were closely correlated with the prognosis of rectal adenocarcinomas through the K-M survival analysis.Conclusion We constructed a prognostic model of rectal adenocarcinomas based on four immune-related lncRNAs by analyzing the data based on TCGA database,with high prediction accuracy.We also identified two biomarkers with poor prognosis(PXN-AS1 and AL158152.2)and one biomarker with good prognosis(LINC01871).
基金a grant from the Health Commission of Hubei Province Scientific Research Project(No.WJ2019M118).
文摘Objective The aim of this study was to construct a prognostic model of esophageal adenocarcinoma(EAC)based on immune-related long noncoding RNAs(immune-related lncRNAs)and identify prognostic biomarkers using the Cancer Genome Atlas(TCGA)database.Methods Whole genomic mRNA expression and clinical data of esophageal adenocarcinoma were obtained from the TCGA database.The software Strawberry Perl,R and R packets were used to identify the immune-related genes and lncRNAs of esophageal adenocarcinoma,and for data processing and analysis.The differentially expressed lncRNAs were detected while comparing esophageal adenocarcinoma and normal tissue samples.The key immune-related lncRNAs were screened using lasso regression analysis and univariate cox regression analysis,and used to construct the prognostic model using multivariate cox regression analysis.To evaluate the accuracy of the risk prognostic model,all esophageal adenocarcinomas were divided into high-risk and low-risk groups according to the median risk score,after which Kaplan-Meier(K-M)survival curves,operating characteristic(ROC)curve and independent prognostic analysis of clinical traits were created.In addition,statistically significant immune-related lncRNAs and potential prognostic biomarkers were identified using the prognostic model and multifactor cox regression analysis for k-m survival analysis.Results A total of 1322 differentially expressed immune-related lncRNAs were identified,28 of which were associated with prognosis via univariate cox regression analysis.In addition,K-M survival analysis showed that the total survival time of the higher risk group was significantly shorter than that of the lower risk group(P=1.063e-10).The area under the ROC curve of 5-year total survival rate was 0.90.The risk score showed independent prognostic risk for esophageal adenocarcinoma via single factor and multifactorial independent prognostic analyses.In addition,the HR and 95%CI of each key immune-related lncRNA were calculated using multivariate Cox regression.Using k-m survival analysis,we found that 5 out of 12 key significant immune-related lncRNAs had independent prognostic value[AL136115.1(P=0.006),AC079684.1(P=0.008),AC07916394.1(P=0.0386),AC087620.1(P=0.041)and MIRLET7BHG(P=0.044)].Conclusion The present study successfully constructed a prognostic model of esophageal adenocarcinoma based on the TCGA database,with moderate predictive accuracy.The model consisted of the expression level of 12 immune-related lncRNAs.Furthermore,the study identified one favorable prognostic biomarker,MIRLET7BHG,and four poor prognostic biomarkers(AL136115.1,AC079684.1,AC016394.1,and AC087620.1).
文摘With the wide application of immunotherapy drug PD-1/PD-L1 inhibitor in China and the continuous clinical research,a major problem that we have to face is the immune-related pneumonia caused by PD-1/PD-L1.At present,western medicine mainly treated it by hormone therapy,which may cause side effects,such as obesity,osteoporosis and osteonecrosis for hormone therapy by long-term,and increase the patients'pain.Under the guidance of the theory of syndrome differentiation,traditional Chinese medicine(TCM)advocates the methods of expelling wind and clearing away cold,resolving phlegm and relieving asthma,relieving heat from lung,and invigorating the spleen and tonifying the kidney,etc.Exact differentiation of symptoms and rational usage of drugs can play an important role in the early prevention and treatment of immune-related pneumonia,reflecting the important role of TCM in the prevention and treatment of side effects of new drugs.In order to provide an effective clinical reference for clinicians in the practice of using PD-1/PD-L1,this paper systematically reviewed the use of TCM in the treatment of immune-related pneumonia induced by PD-1/PD-L1 inhibitors.
