Jiajing Wang and Jianfeng Shu* Pages 1539 - 1560 ( 22 )
Background: RNA methylation modification is not only intimately interrelated with cancer development and progression but also actively influences immune cell infiltration in the tumor microenvironment (TME). RNA methylation modification genes influence the therapeutic progression of lung adenocarcinoma (LUAD), and mining RNA methylation modification prognosis-related markers in LUAD is crucial for its precise prognosis.
Methods: RNA-Seq data and Gene sets were collected from online databases or published literature. Genomic variation analysis was conducted by the Maftools package. RNA methylation-immune-related lncRNAs were obtained by Pearson correlation analysis. Then, Consistent clustering analysis was performed to obtain RNA methylation modification- immune molecular subtypes (RMM-I Molecular subtypes) in LUAD based on selected lncRNAs. COX and random survival forest analysis were carried out to construct the RMM-I Score. The receiver operating characteristic (ROC) curve and Kaplan Meier survival analysis were used to assess survival differences. Tumor immune microenvironment was assessed through related gene signatures and CIBERSORT algorithm. In addition, drug sensitivity analysis was executed by the pRRophetic package.
Results: Four RNA methylation modified-immune molecular subtypes (RMM-I1, RMM- I2, RMM-I3, RMM-I4) were presented in LUAD. Patients in RMM-I4 exhibited excellent survival advantages and immune activity. HAVCR2, CD274, and CTLA-4 expression were activated in RMM-I4, which might be heat tumors and a potential beneficial group for immunotherapy. OGFRP1, LINC01116, DLGAP1-AS2, CRNDE, LINC01137, MIR210HG, and CYP1B1-AS1 comprised the RMM-I Score. The RMM-I Score exhibited excellent accuracy in the prognostic assessment of LUAD, as patients with a low RMM- I Score exhibited remarkable survival advantage. Patients with a low RMM-I score might be more sensitive to treatment with Docetaxel, Vinorelbine, Paclitaxel, Cisplatin, and immunotherapy.
Conclusion: The RMM-I molecular subtype constituted the novel molecular characteristic subtype of LUAD, which complemented the existing pathological typing. More refined and accurate molecular subtypes provide help to reveal the mechanism of LUAD development. In addition, the RMM-I score offers a reliable tool for accurate prognosis of LUAD.
Lung adenocarcinoma, RNA methylation, post translational modification, RMM-I molecular subtypes, RMM-I score, LUAD.