A Prognostic Risk Score Based on Genes related with m 7 G regulators for the Prognosis and Immunotherapy Response of Lung Adenocarcinoma

Background: Lung adenocarcinoma (LUAD) is the most common subtype of lung cancer and is significantly correlated with poor prognosis. N 7 -methylguanosine (m 7 G) modification plays an important role in occurrence, progression, and prognosis of cancer. The present study aimed to construct a prognostic risk model based on m 7 G-related genes for LUAD. Methods: In this study, we used data from TCGA-LUAD for the training cohort and GSE72049 and GSE31210 for the validation cohorts. Univariate Cox regression, Lasso regression analyses, and multivariate Cox regression analyses were conducted to construct an m 7 G-related genes risk model. We then applied multivariate Cox regression, Kaplan-Meier analysis, and Receiver operating characteristic (ROC) curves to evaluate the risk model. Finally, we analyzed the immune microenvironment and immunotherapy response with the risk score model in LUAD. Results: A novel prognostic risk model based on the four m 7 G-related genes (ANLN, KRT6A, NTSR1 and RHOV) was constructed. The multivariate Cox analysis showed that the prognostic risk model was an independent risk factor (HR 1.224, 95% CI 1.162-1.290, P ＜0.001). Patients in the high-risk group showed an increased risk of mortality in training cohort(HR 2.04, 95%CI 1.49-2.79, P ＜0.001) and validation cohorts(HR 2.46, 95%CI 1.7-3.56; HR 3.85, 95%CI 1.98-7.49). The 1, 3, and 5-year AUC value in TCGA was 0.755, 0.71, and 0.631, respectively; The 1, 3, and 5-year AUC value in GSE72049 was 0.709, 0.672, and 0.762, respectively; The 1, 3, and 5-year AUC value in GSE31210 was 0.715, 0.649, and 0.709, respectively. The high-risk patients were more likely to respond to immunotherapy than the low-risk group( P ＜0.001). Conclusion: A novel prognostic risk model based on m 7 G-related genes was established in this study, which may predict clinical prognosis and immunotherapeutic responses in LUAD patients.