Background Pancreatic cancer (PC) is a malignant neoplasm of the digestive tract that is highly malignant and difficult to diagnose at an early stage with high postoperative mortality and low cure rates. Cancer immunotherapy is innovating the clinical treatment of several cancers, but has a limited role in PC. The incomplete understanding of immune response hinders the development of gene therapy. To fill this gap, it is very necessary to classify the immunogenic subtypes of PC to understand the relationship between tumor microenvironments and clinical pathological characteristics, DNA damage repair and tumor immune response.Methods We extracted copy number change, somatic mutation and expression data from tumor genome map (TCGA). Using RNA sequencing data, we defined three different immunophenotypes and elucidated how immune cell interactions in immune subtypes vary with the background of the immune system. Further correlation analysis between DNA damage repair (DDR) related genes expression and immune response was conducted to explore the effects of DDR expression on antitumor activity in the tumor microenvironments.Results We defined three different immunophenotypes and elucidated how immune cell interactions in immune subtypes vary with the background of the immune system. When the total number of mutations was standardized, no enrichment of new epitopes was detected in immunocompetent phenotypes. These observations suggest that mutations in Th-1 enriched IS3 tumors are essentially no more immunogenic than those in IS2 cancers. We also found that the expression patterns of key IFN mediators STAT1 and / or STAT3 were increased in tumors with DDR mutations (19 of ATM, ERCC1, Rb1, BRCA2, pole and TP53), which is a reflex activation of IFN pathway.Conclusions Three defined immune subtypes show different characteristics of immune cell infiltration, revealing different manifestations in anti-cancer immune function. That is to say, clinical biological events of differential tumors are associated to immune-phenotypes. The invasive phenotype was driven by somatic mutations across immune subtypes, and DDR defect may also influence the response of tumor immune subtypes. Our results suggested that the occurrence of pancreatic cancer is related to genetic factors of immunophenotype, providing information for clinical prognosis and outcome of pancreatic cancer.
Objective: The main aim of this study was to identify immune-related genes in Kidney clear cell carcinoma (ccRcc) patients.Methods: We downloaded RNAseq data and clinical information of ccRcc patients from the TCGA database and retrieved the immune-related genes list from the web of Immport. We performed Cox and LASSO analyses, using “survival” and “glmnt’ packages implemented in R, to reveal survival immune-related genes. Next, we verified the prognostic signature of these genes, and further confirmed its survival value using Kaplan-Meier analysis and ROC time dependent curves. We also evaluated the signature’s immune cell component and the results of immunotherapy.Results: Analysis of 526 tumor samples revealed a total of 770 immune-related genes, after four steps of primary screening. Cox and LASSO analyses revealed 11 hub immune-related survival genes, namely ADRB2, AGER, BIRC5, CDNF, CXCL2, ESR2, F2RL1, IFITM1, PTX3, SEMA3G, and TCF7L2. Kaplan-Meier curves revealed prognostic signature of the 11 DEGs, with the high-risk score group in ccRcc patients exhibiting a worse survival rate (P<0.001 in both the training and test sets, respectively). ROC analysis in the training set revealed an AUC value of 0.71 for both 1- and 3-year survival, and 0.65 for 5 years). Furthermore compared with low-risk score group, we found that the high-risk score group had a higher percentage of 10 cells in the immune component (Exhausted cells, Tr1 cells, nTreg cells, Th1 cells, Tfh cells, Effect memory cells, MAIT cells, Macrophage cells, CD8 T cells, and iTreg cells), a low percentage of 6 cells (CD4 native cells, CD8 native cells, Th17 cells, central memory cells, Neutrophil cells, and Gamma delta cells).Conclusion: Our results revealed 11 survival immune-related genes (ADRB2, AGER, BIRC5, CDNF, CXCL2, ESR2, F2RL1, IFITM1, PTX3, SEMA3G, TCF7L2) in ccRcc patients. We used these genes to develop a signature that can act as an independent prognostic predictor for overall survival and response of ccRcc patients to immunotherapy.
Objective The main aim of this study was to identify immune-related genes in Kidney clear cell carcinoma (ccRcc) patients. Methods We downloaded RNAseq data and clinical information of ccRcc patients from the TCGA database and retrieved the immune-related genes list from the web of Immport. We performed Cox and LASSO analyses, using “survival” and “glmnt’ packages implemented in R, to reveal survival immune-related genes. Next, we verified the prognostic signature of these genes, and further confirmed its survival value using Kaplan-Meier analysis and ROC time dependent curves. We also evaluated the signature’s immune cell component and the results of immunotherapy. Results Analysis of 526 tumor samples revealed a total of 770 immune-related genes, after four steps of primary screening. Cox and LASSO analyses revealed 11 hub immune-related survival genes, namely ADRB2, AGER, BIRC5, CDNF, CXCL2, ESR2, F2RL1, IFITM1, PTX3, SEMA3G, and TCF7L2. Kaplan-Meier curves revealed prognostic signature of the 11 DEGs, with the high-risk score group in ccRcc patients exhibiting a worse survival rate (P < 0.001 in both the training and test sets, respectively). ROC analysis in the training set revealed an AUC value of 0.71 for both 1- and 3-year survival, and 0.65 for 5 years). Furthermore compared with low-risk score group, we found that the high-risk score group had a higher percentage of 10 cells in the immune component (Exhausted cells, Tr1 cells, nTreg cells, Th1 cells, Tfh cells, Effect memory cells, MAIT cells, Macrophage cells, CD8 T cells, and iTreg cells), a low percentage of 6 cells (CD4 native cells, CD8 native cells, Th17 cells, central memory cells, Neutrophil cells, and Gamma delta cells). Conclusion Our results revealed 11 survival immune-related genes (ADRB2, AGER, BIRC5, CDNF, CXCL2, ESR2, F2RL1, IFITM1, PTX3, SEMA3G, TCF7L2) in ccRcc patients. We used these genes to develop a signature that can act as an independent prognostic predictor for overall survival and response of ccRcc patients to immunotherapy.
Immune-related genes are important factors in tumor progression. The main aim of this study was to identify the immune-related genes in Kidney papillary cell carcinoma (pRCC) patients. We downloaded RNAseq data and clinical information of pRCC patients from the TCGA database and retrieved the immune-related genes list from Immport. From the data, we mined out 2468 differential expression genes (DEGs) and 183 immune-related DEGs. Four hub DEGs (NTS, BIRC5, ELN, and CHGA) were identified after conducting Cox analysis and LASSO analysis. Moreover, the prognostic value of the signature based on 4 hub DEGs was verified using Kaplan-Meier analysis (P=0.0041 in the training set and p=0.021 in the test set) and ROC analysis (AUC: 0.957 in 1 year, 0.965 in 2 years, and 0.901 in 3 years in the training set, and 0.963 in 1 year, 0.898 in 2 years, and 0.742 in 3 years in the test set). Furthermore, we found that the high-risk score group had a higher percentage of B cells in the immune component, a higher expression of immune-related genes (CTLA4, LAG3, PDCD1LG2, and TIGIT), and a better immunotherapy response.
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