Clear cell renal cell carcinoma (ccRCC) is known for its high drug resistance. The tumor-immune crosstalk mediated by the epigenetic regulation of N6-methyladenosine (m6A) modification has been demonstrated in recent studies. Therefore, m6A modification-mediated immune cell infiltration characteristics may be helpful to guide immunotherapy for ccRCC.
This study comprehensively analyzed m6A modifications using the clinical parameters, single-cell RNA sequencing data, and bulk RNA sequencing data from the TCGA-ccRC cohort and 13 external validation cohorts. A series of bioinformatic approaches were applied to construct an m6A regulator prognostic risk score (MRPRS) to predict survival and immunotherapy response in ccRCC patients. Immunological characteristics, enriched pathways, and mutation were evaluated in high- and low-MRPRS groups.
The expressional alteration landscape of m6A regulators was profiled in ccRCC cell clusters and tissue. The 8 regulator genes with minimal lambda were integrated to build an MRPRS, and it was positively correlated with immunotherapeutic response in extent validation cohorts. The clinicopathological features and immune infiltration characteristics could be distinguished by the high- and low-MRPRS. Moreover, the MRPRS-mediated mutation pattern has an enhanced response to immune checkpoint blockade in the ccRCC and pan-cancer cohorts.
The proposed MRPRS is a promising biomarker to predict clinical outcomes and therapeutic responses in ccRCC patients.
Frontiers in immunology. 2022 Jun 17*** epublish ***
Mingke Yu, Xuefei Liu, Han Xu, Sangyu Shen, Fajiu Wang, Dajin Chen, Guorong Li, Zongping Wang, Zhixiang Zuo, An Zhao
Experimental Research Center, Cancer Hospital of University of Chinese Academy of Sciences (Zhejiang Cancer Hospital), Hangzhou, China., State Key Laboratory of Oncology in Southern China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, China., Department of Pediatrics, The Affiliated Children's Hospital of Nanchang University (Jiangxi Provincial Children's Hospital), Nanchang, China., The Second School of Clinical Medicine , Zhejiang Chinese Medical University, Hangzhou, China., Department of Cardiothoracic Surgery, Huamei Hospital, University of Chinese Academy of Sciences, Ningbo, China., Kidney Disease Center, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China., Department of Urology, North Hospital, Centre Hospitalier Universitaire (CHU) of Saint-Etienne, University of Jean-Monnet, Saint-Etienne, France., Department of Urology, Cancer Hospital of University of Chinese Academy of Sciences (Zhejiang Cancer Hospital), Hangzhou, China.