Identification of N7-methylguanosine related signature for prognosis and immunotherapy efficacy prediction in lung adenocarcinoma
Zhouhua Li, Wenjun Wang, Juan Wu, Xiaoqun Ye
Abstract
Background Lung adenocarcinoma (LUAD) is one of the most frequent causes of tumor-related mortality worldwide. Recently, the role of N7-methylguanosine (m 7 G) in tumors has begun to receive attention, but no investigation on the impact of m 7 G on LUAD. This study aims to elucidate the significance of m 7 G on the prognosis and immunotherapy in LUAD. Methods Consensus clustering was employed to determine the molecular subtype according to m 7 G-related regulators extracted from The Cancer Genome Atlas (TCGA) database. Survival, clinicopathological features and tumor mutational burden (TMB) analysis were applied to research molecular characteristics of each subtype. Subsequently, “limma” package was used to screen differentially expressed genes (DEGs) between subtypes. In the TCGA train cohort ( n = 245), a prognostic signature was established by univariate Cox regression, lasso regression and multivariate Cox regression analysis according to DEGs and survival analysis was employed to assess the prognosis. Then the prognostic value of the signature was verified by TCGA test cohort ( n = 245), TCGA entire cohort ( n = 490) and GSE31210 cohort ( n = 226). Moreover, the association among immune infiltration, clinical features and the signature was investigated. The immune checkpoints, TMB and tumor immune dysfunction and exclusion (TIDE) were applied to predict the immunotherapy response. Results Two novel molecular subtypes (C1 and C2) of LUAD were identified. Compared to C2 subtype, C1 subtype had poorer prognosis and higher TMB. Subsequently, the signature (called the “m 7 G score”) was constructed according to four key genes ( E2F7 , FAM83A , PITX3 , and HOXA13 ). The distribution of m 7 G score were significantly different between two molecular subtypes. The patients with lower m 7 G score had better prognosis in TCGA train cohort and three verification cohort. The m 7 G score was intensively related to immune infiltration. Compared with the lower score, the higher m 7 G score was related to remarkable upregulation of the PD-1 and PD-L1, the higher TMB and the lower TIDE score. Conclusion This study established a m 7 G-related signature for predicting prognosis and immunotherapy in LUAD, which may contribute to the development of new therapeutic strategies for LUAD.