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

Abstract

Background Few studies have demonstrated that the relationship between m6A-related genes and the prognosis, tumor microenvironment and drug resistance of LC. Methods The main results were analyzed with bioinformatics methods. Results Hence, 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. Conclusion In 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.

Identification of One-carbon metabolism-related gene signature and Analysis of the role of m6A and miRNAs/circRNAs for colon adenocarcinoma

“…was positive correlated with AHCY and cyclopamine was positive correlation with AHCY, while Erlotinib and STF-62247 were all nagtive correlation with BHMT, indicating that the one-carbon metabolism-related gene signature was related to drug sensitivity and COAD patients may bene t from these chemotherapy agents. In our study , drug sensitivity screen and validation showed that TGX221, a kind of PI3K-β inhibitor [49], might be the most potential drug in the one-carbon metabolism -dysregulated pathway.…”

Exploration of biological significance of m6A-related genes in Wilms tumor

“…In recent years, more and more studies have con rmed that m6A-related genes are closely related to malignant tumors. For example, ZC3H13, CBLL1, ELAVL1 and YTHDF1 are differentially expressed in lung cancer tissues, which is of great signi cance for the prediction and treatment of lung cancer [27].…”

Roles of RNA Methylations in Cancer Progression, Autophagy, and Anticancer Drug Resistance

“…m6A modification is reversibly modulated through the installation of methyl transferases (writers), the removal of a methyl group by demethylases (erasers), and the recognition of m6A binding proteins (readers) [ 22 , 23 ]. m6A writers and associated proteins (m6A writer complex) include Vir-like m6A methyl transferase-associated protein (VIRMA) [ 24 ], methyl transferase-like protein 3 (METTL3) [ 25 ], METTL4 [ 26 ], MTTL5 [ 27 ], METTL14 [ 28 ], METTL 16 [ 29 ], Wilms’ tumor 1 associated protein (WTAP) [ 30 , 31 ], RNA-binding motif protein 15/15B (RBM15/15B) [ 32 ], casitas B-lineage lymphoma-transforming sequence-like protein 1 (CBLL1) [ 33 ], zinc finger CCCH-type containing 13 (ZC3H13), and zinc finger CCHC-type containing 4 (ZCCHC4) [ 5 , 34 , 35 , 36 , 37 , 38 ]. RBM15/15B, VIRMA, CBLL1, ZCCHC4, and ZC3H13 act as associated proteins of m6A writers.…”