Construction of a Novel Prognostic Model in Lung Adenocarcinoma Based on 7-Methylguanosine-Related Gene Signatures

Abstract

Increasing evidence has implicated the modification of 7-methylguanosine (m7G), a type of RNA modification, in tumor progression. However, no comprehensive analysis to date has summarized the predicted role of m7G-related gene signatures in lung adenocarcinoma (LUAD). Herein, we aimed to develop a novel prognostic model in LUAD based on m7G-related gene signatures. The LUAD transcriptome profiling data and corresponding clinical data were acquired from the Cancer Genome Atlas (TCGA) and two Gene Expression Omnibus datasets. After screening, we first obtained 29 m7G-related genes, most of which were upregulated in tumor tissues and negatively associated with overall survival (OS). According to the expression similarity of m7G-related genes, the combined samples from the TCGA-LUAD and GSE68465 datasets were further classified as two clusters that exhibit distinct OS rates and genetic heterogeneity. Then, we constructed a novel prognostic model involving four genes by using 130 differentially expressed genes among the two clusters. The combined samples were randomly divided into a training cohort and an internal validation cohort in a 1:1 ratio, and the GSE72094 dataset was used as an external validation cohort. The samples were divided into high- and low-risk groups. We demonstrated that a higher risk score was an independent negative prognostic factor and predicted poor OS. A nomogram was further constructed to better predict the survival of LUAD patients. Functional enrichment analyses indicated that cell cycle and DNA replication-related biological processes and pathways were enriched in the high-risk group. More importantly, the low-risk group had greater infiltration and enrichment of most immune cells, as well as higher ESTIMATE, immune, and stromal scores. In addition, the high-risk group had a lower TIDE score and higher expressions of most immune checkpoint-related genes. We finally noticed that patients in the high-risk group were more sensitive to chemotherapeutic agents commonly used in LUAD. In conclusion, we herein summarized for the first time the alterations and prognostic role of m7G-related genes in LUAD and then constructed a prognostic model based on m7G-related gene signatures that could accurately and stably predict survival and guide individualized treatment decision-making in LUAD patients.