AUTHOR=Yu Mingke , Liu Xuefei , Xu Han , Shen Sangyu , Wang Fajiu , Chen Dajin , Li Guorong , Wang Zongping , Zuo Zhixiang , Zhao An 

TITLE=Comprehensive Evaluation of the m6A Regulator Prognostic Risk Score in the Prediction of Immunotherapy Response in Clear Cell Renal Cell Carcinoma

JOURNAL=Frontiers in Immunology

VOLUME=Volume 13 - 2022

YEAR=2022

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2022.818120

DOI=10.3389/fimmu.2022.818120

ISSN=1664-3224

ABSTRACT=Background: Clear cell renal cell carcinoma (ccRCC) is known for its high drug resistance. The tumor-immune crosstalk mediated by 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.
Methods: This study comprehensively analyzed the m6A modifications using the clinical parameters, single-cell RNA sequencing data and bulk RNA sequencing data from the TCGA-RCC cohort and 13 external validation cohorts. A series of bioinformatic approaches were applied to construct m6A regulator prognostic risk score (MRPRS) to predict survival and immunotherapy response in RCC patients. Immunological characteristics, enriched pathways, and mutation were evaluated in high- and low-MRPRS groups.
Results: The expressional alteration landscape of m6A regulators was profiled in ccRCC cells 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 with an enhanced response to immune checkpoint blockade in ccRCC and pan-cancer cohort.
Conclusions: The proposed MRPRS is a promising biomarker to predict clinical outcomes and therapeutic responses in ccRCC patients.