Comprehensive Analysis of Tumor Immune Microenvironment and Prognosis of m6A-Related IncRNAs in Lung Adenocarcinoma.

Abstract

Lung cancer is a fatal disease with high morbidity and mortality. As a major type of non-small cell lung cancer (NSCLC), lung adenocarcinoma (LUAD) has come into the focus of the biological and clinical research. Nevertheless, potential functions of N6-methyladenosine (m6A) methylation-related long non-coding RNAs (lncRNAs) in the tumor immune microenvironment (TIME) remain unclear. Here, we analyzed RNA-seq data of 522 samples from the TCGA-LUAD project. Based on integrative analyses of lncRNA, immune, and clinical profiles, we developed a computational method to determine the characteristics of lncRNAs as an indicators of immune cell infiltration in LUAD patients. Subsequently, we investigated the influence of m6A-related lncRNAs on prognosis and immunotherapy in patients with LUAD. We identified 24 m6A-related lncRNAs that were related to LUAD prognosis and clustered in two molecular subtypes (clusters 1 and 2). Our results suggest that cluster 1 was significantly related to downregulation of PD-L1, enhancement of immune cell infiltration, and good prognosis. Furthermore, p53 and mTOR pathways were enriched in cluster 1, whereas in the cluster 2, PPAR was uncommonly enriched. Patients with LUAD who had lower risk scores exhibited higher immunoscores and lower expression levels of programmed cell death-ligand 1, compared with patients who had higher risk scores. Finally, m6A-related lncRNAs were implicated in the TIME; our findings indicate that these lncRNAs are critical within the TIME in LUAD. These signatures are promising as potential targets for improved LUAD immunotherapy.