AUTHOR=Ma Yanpin , Zhang Huping 

TITLE=Genomics and Prognosis Analysis of N6-Methyladenosine Regulators in Lung Adenocarcinoma

JOURNAL=Frontiers in Genetics

VOLUME=12

YEAR=2021

URL=https://www.frontiersin.org/journals/genetics/articles/10.3389/fgene.2021.746666

DOI=10.3389/fgene.2021.746666

ISSN=1664-8021

ABSTRACT=<p><bold>Objective:</bold> N<sup>6</sup>-methyladenosine (m<sup>6</sup>A) modification is involved in modulating various biological processes in human cancers. But the implication of m<sup>6</sup>A modification in lung adenocarcinoma (LUAD) is still unclear. Hence, this study conducted a comprehensive analysis of the expression and clinical implication of m<sup>6</sup>A regulators in LUAD.</p><p><bold>Methods:</bold> Consensus clustering analysis of 502 LUAD samples in the TCGA dataset was presented based on the expression profiles of 20 m<sup>6</sup>A regulators using ConsensusClusterPlus package. Overall survival (OS), activation of signaling pathways and tumor immunity (immune/stromal score, tumor purity, expression of HLA and immune checkpoints, and immune cell infiltration) were compared between m<sup>6</sup>A modification patterns. The m<sup>6</sup>A-related genes between patterns were identified and prognostic m<sup>6</sup>A-related genes were imported into LASSO-cox regression analysis. The m<sup>6</sup>A risk score was developed and its prognostic implication was evaluated and externally verified in the GSE30219 and GSE72094 dataset. Furthermore, a nomogram that contained independent prognostic indicators was established, followed by external verification.</p><p><bold>Results:</bold> Two m<sup>6</sup>A modification patterns were clustered across LUAD based on the expression similarity of the m<sup>6</sup>A regulators via consensus clustering analysis, with distinct OS, activation of signaling pathways and tumor immunity. Totally, 213 m<sup>6</sup>A-related genes that were identified by comparing two patterns were significantly related to LUAD prognosis. By LASSO method, we constructed the m<sup>6</sup>A risk score that was a reliable and independent prognostic factor for LUAD. Patients with low m<sup>6</sup>A risk score displayed a prominent survival advantage. After incorporating independent clinical features, we developed the prognostic nomogram that exhibited high predictive accuracy and the best clinical net benefit for OS.</p><p><bold>Conclusion:</bold> Collectively, our study may provide a clinically useful tool for precise prognostic management and optimization of immunotherapeutic strategies for LUAD patients.</p>