Abstract
We analyzed the prognostic value of N6-methyladenosine (m6A) regulatory genes in lung adenocarcinoma (LADC) and their association with tumor immunity and immunotherapy response. Seventeen of 20 m6A regulatory genes were differentially expressed in LDAC tissue samples from the TCGA and GEO databases. We developed a five-m6A regulatory gene prognostic signature based on univariate and Lasso Cox regression analysis. Western blot analysis confirmed that the five prognostic m6A regulatory proteins were highly expressed in LADC tissues. We constructed a nomogram with five-m6A regulatory gene prognostic risk signature and AJCC stages. ROC curves and calibration curves showed that the nomogram was well calibrated and accurately distinguished high-risk and low-risk LADC patients. Weighted gene co-expression analysis showed significant correlation between prognostic risk signature genes and the turquoise module enriched with cell cycle genes. The high-risk LADC patients showed significantly higher PD-L1 levels, increased tumor mutational burden, and a lower proportion of CD8+ T cells in the tumor tissues and improved response to immune checkpoint blockade therapy. These findings show that this five-m6A regulatory gene signature is a prognostic biomarker in LADC and that immune checkpoint blockade is a potential therapeutic option for high-risk LADC patients.