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

Ming Zhong; Xiaohua Wang; Enyi Zhu; Lian Gong; Lingyan Fei; Liang Zhao; Keping Wu; Chun Tang; Lizhen Zhang; Zhongli Wang; Zhihua Zheng

doi:10.3389/fgene.2022.905051

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

Front Genet. 2022 Jun 29:13:905051. doi: 10.3389/fgene.2022.905051. eCollection 2022.

Authors

Ming Zhong¹, Xiaohua Wang¹, Enyi Zhu¹, Lian Gong², Lingyan Fei¹, Liang Zhao³, Keping Wu¹, Chun Tang¹, Lizhen Zhang⁴, Zhongli Wang⁵, Zhihua Zheng¹

Affiliations

¹ Department of Nephrology, Center of Kidney and Urology, The Seventh Affiliated Hospital, Sun Yat-sen University, Shenzhen, China.
² Department of Oncology, Third Xiangya Hospital, Central South University, Changsha, China.
³ National Clinical Research Center for Child Health, National Children's Regional Medical Center, The Children's Hospital, Zhejiang University School of Medicine, Hangzhou, China.
⁴ Department of Urology, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.
⁵ Department of Internal Medicine and Geriatrics, Zhongnan Hospital, Wuhan University School of Medicine, Wuhan, China.

Abstract

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.

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