4.6 Article

Analysis of Pyroptosis-Related Immune Signatures and Identification of Pyroptosis-Related LncRNA Prognostic Signature in Clear Cell Renal Cell Carcinoma

期刊

FRONTIERS IN GENETICS
卷 13, 期 -, 页码 -

出版社

FRONTIERS MEDIA SA
DOI: 10.3389/fgene.2022.905051

关键词

clear cell renal cell carcinoma; pyroptosis; tumor microenvironment; long noncoding RNA; immune

向作者/读者索取更多资源

This study systematically investigated the role of pyroptosis in clear cell renal cell carcinoma (ccRCC) and identified different subtypes with varied clinical outcomes, immune signatures, and responses to immunotherapy. Activation of pyroptosis was found to promote tumor progression by facilitating immune cell infiltration. A high pyroptosis-score was associated with an unfavorable immune environment and worse prognosis. The study also constructed a prognostic model based on pyroptosis-related long noncoding RNAs (PRlncRNAs) and explored the relationship between high- and low-risk groups with tumor microenvironment, immune infiltration, and drug therapy.
Clear cell renal cell carcinoma (ccRCC) is a common urinary system malignant tumor with a high incidence and recurrence rate. Pyroptosis is a kind of programmed cell death caused by inflammasomes. More and more evidence had confirmed that pyroptosis plays a very significant part in cancer, and it is controversial whether pyroptosis promotes or inhibits tumors. Consistently, its potential role in ccRCC treatment efficacy and prognosis remains unclear. In this study, we systematically investigated the role of pyroptosis in the ccRCC samples from The Cancer Genome Atlas (TCGA) database. Based on the differentially expressed pyroptosis-related genes (DEPRGs), we identified three pyroptosis subtypes with different clinical outcomes, immune signatures, and responses to immunotherapy. Gene set variation analysis (GSVA), Gene Ontology (GO) analysis, and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis revealed that pyroptosis activation meant infiltration of more immune cells that is conducive to tumor progression. To further investigate the immunomodulatory effect of pyroptosis in ccRCC, we constructed a pyroptosis-score based on the common differential prognostic genes of the three pyroptosis subtypes. It was found that patients with high pyroptosis-score were in an unfavorable immune environment and the prognosis was worse. Gene set enrichment analysis suggested that immune-related biological processes were activated in the high pyroptosis-score group. Then, the least absolute shrinkage and selection operator (LASSO) Cox regression was implemented for constructing a prognostic model of eight pyroptosis-related long noncoding RNAs (PRlncRNAs) in the TCGA dataset, and the outcomes revealed that, compared with the low-risk group, the model-based high-risk group was intently associated with poor overall survival (OS). We further explored the relationship between high- and low-risk groups with tumor microenvironment (TME), immune infiltration, and drug therapy. Finally, we constructed and confirmed a robust and reliable PRlncRNA pairs prediction model of ccRCC, identified PRlncRNA, and verified it by experiments. Our findings suggested the potential role of pyroptosis in ccRCC, offering new insights into the prognosis of ccRCC and guiding effectual targeted therapy and immunotherapy.

作者

我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。

评论

主要评分

4.6
评分不足

次要评分

新颖性
-
重要性
-
科学严谨性
-
评价这篇论文

推荐

暂无数据
暂无数据