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Identification of pyroptosis-related subtypes and comprehensive analysis of characteristics of the tumor microenvironment infiltration in clear cell renal cell carcinoma.

ABSTRACT: Pyroptosis is a kind of programmed cell death triggered by the inflammasome. Growing evidence has revealed the crucial utility of pyroptosis in tumors. However, the potential mechanism of pyroptosis in clear cell renal cell carcinoma (ccRCC) is still unclear. In this research, we systematically analyze the genetic and transcriptional alterations of pyroptosis-related genes (PRGs) in ccRCC, identify pyroptosis-related subtypes, analyze the clinical and microenvironmental differences among different subtypes, develop a corresponding prognostic model to predict the prognosis of patients, and interpret the effect of pyroptosis on ccRCC microenvironment. This study provides a new perspective for a comprehensive understanding of the role of pyroptosis in ccRCC and its impact on the immune microenvironment, and a reliable scoring system was established to predict patients' prognosis.

SUBMITTER: Zeng J

PROVIDER: S-EPMC10519968 | biostudies-literature | 2023 Sep

REPOSITORIES: biostudies-literature

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Identification of pyroptosis-related subtypes and comprehensive analysis of characteristics of the tumor microenvironment infiltration in clear cell renal cell carcinoma.

Zeng Jiayi J Zhu Ping P Tang Yanlin Y Zhang Changzheng C Ye Chujin C Cheng Shouyu S Tian Kaiwen K Yang Bowen B Zeng Weinan W Liu Yanjun Y Xian Zhiyong Z Yu Yuming Y

Scientific reports 20230925 1

Pyroptosis is a kind of programmed cell death triggered by the inflammasome. Growing evidence has revealed the crucial utility of pyroptosis in tumors. However, the potential mechanism of pyroptosis in clear cell renal cell carcinoma (ccRCC) is still unclear. In this research, we systematically analyze the genetic and transcriptional alterations of pyroptosis-related genes (PRGs) in ccRCC, identify pyroptosis-related subtypes, analyze the clinical and microenvironmental differences among differe ...[more]

PMID: 37749171

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Project description:BackgroundIt is well known that chronic inflammation can promote the occurrence and progression of cancer. As a type of proinflammatory death, pyroptosis can recast a suitable microenvironment to promote tumor growth. However, the potential role of pyroptosis in clear cell renal cell carcinoma (ccRCC) remains unclear.MethodsThe transcriptome expression profile and mutation profile data of ccRCC with clinical characteristics included in this study were obtained from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. Consensus clustering was used for clustering. Gene set enrichment analysis (GSEA) analysis were applied to evaluate the biological mechanisms. Single sample gene set enrichment analysis (ssGSEA) was applied for evaluating the proportion of various immune infiltrating cells. The ESTIMATE algorithm was involved to compute the immune microenvironment scores.ResultsAmong the 17 pyroptosis regulators, a total of 15 pyroptosis regulators were differential expressed between tumor and normal tissues, in which 12 of them emerged strong correlations with prognoses. According to the pyroptosis components, the ccRCC patients were divided into four pyroptosis subtypes with different clinical, molecular, and pathway characteristics. Compared with other clusters, cluster B showed the pyroptosis heat phenotype, while cluster D represented the pyroptosis cold phenotype with poor overall survival. In addition, we performed principal component analysis (PCA) on the differential genes between clusters to construct the pyroptosis index. Furthermore, the pyroptosis index was significantly correlated with survival in different tumor mutation statuses and different grades and stages. Besides, the expression of pyroptosis-related regulators was related to the infiltration of immune cells and the expression of immune checkpoints, among which AIM2 was considered as the most significant immune-related pyroptosis regulator. Ultimately, we found that AIM2 was related to the immune activation pathway and was significantly overexpressed in tumor tissues.ConclusionThis study revealed that pyroptosis regulators and pyroptosis index played an important role in the development and prognoses of ccRCC. Moreover, AIM2 can be used as a predictor of the response of immunotherapy. Assessing the pyroptosis patterns may help evaluate the tumor status and guide immunotherapy strategies.

Project description:BackgroundOne of the most fatal forms of cancer of the urinary system, renal cell carcinoma (RCC), significantly negatively impacts human health. Recent research reveals that abnormal glycosylation contributes to the growth and spread of tumors. However, there is no information on the function of genes related to glycosylation in RCC.MethodsIn this study, we created a technique that can be used to guide the choice of immunotherapy and chemotherapy regimens for RCC patients while predicting their survival prognosis. The Cancer Genome Atlas (TCGA) provided us with patient information, while the GeneCards database allowed us to collect genes involved in glycosylation. GSE29609 was used as external validation to assess the accuracy of prognostic models. The "ConsensusClusterPlus" program created molecular subtypes based on genes relevant to glycosylation discovered using differential expression analysis and univariate Cox analysis. We examined immune cell infiltration as measured by estimate, CIBERSORT, TIMER, and ssGSEA algorithms, Tumor Immune Dysfunction and Exclusion (TIDE) and exclusion of tumour stemness indices (TSIs) based on glycosylation-related molecular subtypes and risk profiles. Stratification, somatic mutation, nomogram creation, and chemotherapy response prediction were carried out based on risk factors.ResultsWe built and verified 16 gene signatures associated with the prognosis of ccRCC patients, which are independent prognostic variables, and identified glycosylation-related genes by bioinformatics research. Cluster 2 is associated with lower human leukocyte antigen expression, worse overall survival, higher immunological checkpoints, and higher immune escape scores. In addition, cluster 2 had significantly better angiogenic activity, mesenchymal EMT, and stem ability scores. Higher immune checkpoint genes and human leukocyte antigens are associated with lower overall survival and a higher risk score. Higher estimated and immune scores, lesser tumor purity, lower mesenchymal EMT, and higher stem scores were all characteristics of the high-risk group. High amounts of tumor-infiltrating lymphocytes, a high mutation load, and a high copy number alteration frequency were present in the high-risk group.Discussion.According to our research, the 16-gene prognostic signature may be helpful in predicting prognosis and developing individualized treatments for patients with renal clear cell carcinoma, which may result in new personalized management options for these patients.

Dataset Information

Identification of pyroptosis-related subtypes and comprehensive analysis of characteristics of the tumor microenvironment infiltration in clear cell renal cell carcinoma.

Publications

Identification of pyroptosis-related subtypes and comprehensive analysis of characteristics of the tumor microenvironment infiltration in clear cell renal cell carcinoma.

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