Study on the prognosis, immune and drug resistance of m6A-related genes in lung cancer

Abstract

BackgroundFew studies have demonstrated that the relationship between m6A-related genes and the prognosis, tumor microenvironment and drug resistance of LC.MethodsThe main results were analyzed with bioinformatics methods.ResultsHence, we found 10 m6A-related genes expressed less in tumor samples in comparison with normal ones. Using consensus clustering, all LC patients were grouped into 2 subgroups according to the overall expression of 10 differential expressed m6A-related genes. In two clusters, the OS and immune characteristics were different. We analyzed the predictive potential of 10 m6A-related genes in the prognosis of LC, and obtained a risk prognosis model on the strength of ZC3H13, CBLL1, ELAVL1 and YTHDF1 as the hub candidate genes through LASSO cox. The expression of 4 hub m6A-related genes was validated by IHC in the HPA database. The infiltration level of dendritic cell, CD4+ T cell and neutrophil that were affected by CNV level of m6A-related genes in LUAD and LUSC patients. Moreover, based on GSCALite database, we found that LUSC patients with hypermethylation tended to have a better overall survival. In terms of drug sensitivity, etoposide correlated negatively with ELAVL1, HNRNPC, RBM15B, YTHDF2 and CBLL1. ZC3H13 had positively association with afatinib, while HNRNPC was positively associated with dasatinib, erlotinib, lapatinib and TGX221. Crizotinib had a negative correlation with ELAVL1, CBLL1, HNRNPC and RBM15B.ConclusionIn conclusion, m6A-related genes are important participants in LC and the expression levels of ZC3H13, CBLL1, ELAVL1 and YTHDF1 are significant for prediction and treatment of LC. Researches of drug resistance based on m6A-related genes need to pay more attention for producing new therapeutic strategies of LC and CBLL1 may contribute to target treatment for further research.