m6A Regulators Is Differently Expressed and Correlated With Immune Response of Esophageal Cancer

Abstract

N6 methyladenosine (m6A) RNA methylation regulators play an important role in the development of tumors. However, their function in esophageal cancer (EC) has not been fully elucidated. Here, we analyzed the gene expression data of 24 major m6A RNA methylation regulators from 775 patients with EC from TCGA dataset. The present study showed the aberrations of m6A regulators in genome were correlated to prognosis in human ECs. Meanwhile, 17 m6A regulators showed increased expression in EC samples, including YTHDC1, IGF2BP2, FTO, METTL14, YTHDF3, RBM15, WTAP, HNRNPA2B1, HNRNPC, ALKBH5, YTHDF2, METTL16, IGF2BP3, VIRMA, RBM15B, YTHDF1, KIAA1429, HAKAI, and ZC3H13. Among them, we found HNRNPC, YTHDC2, WTAP, VIRMA, IGF2BP3, and HNRNPA2B1 were significantly correlated to worse outcomes and advanced stage in EC. Furthermore, we showed levels of m6A regulators is correlated with the expression of Immuno-regulators (Immunoinhibitors, Immunostimulators, and MHC molecules) and immune infiltration levels in EC. Bioinformatics further confirm m6A regulators were involved in regulating RNA splicing, RNA stability, and cell proliferation. Our study showed m6A regulators are promising targets and biomarkers for cancer immunotherapy in EC.

N6-Methyladenosine in Cancer Immunotherapy: An Undervalued Therapeutic Target

“…Moreover, low m 6 A score, characterized by increased mutation burden and activation of immunity, indicates an inflamed TME phenotype and enhanced response to anti-PD-1/L1 immunotherapy in gastric cancer (GC) (65). In addition, m 6 A-related signature has been identified as biomarker for tumor immune phenotypes and anti-PD-1 immunotherapy treatment response in lung adenocarcinoma (LADC) (72,73), stomach adenocarcinomas (STADs) (74), Esophageal squamous cell carcinoma (ESCC) (75,76), Renal Papillary Cell Carcinoma (RPCC), Hepatocellular Carcinoma (HCC) (77,78). These statistic results together indicate that m 6 A modification may reflect TME status and predict immunotherapy efficacy in pan-cancers instead of limited to specific cancer types.…”

Effects of RNA methylation N6-methyladenosine regulators on malignant progression and prognosis of melanoma

“…Several evidences have displayed the involvement of m6A regulators modification in innate and adaptive immune responses [ 42 , 46 ], but its mechanism of shaping the tumor microenvironment in melanoma remains poorly understood. We have verified the oncogenic functions of IGF2BP3 in melanoma via cell functional experiments.…”

The m6A RNA Modification Quantity and mRNA Expression Level of RNA Methylation-Related Genes in Head and Neck Squamous Cell Carcinoma Cell Lines and Patients

“…Accumulating data indicates the significant role of m 6 A RNA modification in the post-transcriptional regulation of gene expression that determines the proper function of crucial physiological processes. Therefore, disturbances in m 6 A RNA methylation may lead to the development of pathological changes, including cancers [ 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 ]. HNSCC initiation, progression, and growth are complex molecular processes encompassing genetic and epigenetic alterations.…”

“…To date, only a few studies indicated the essential regulatory role of m 6 A post-transcriptional modification and RNA methylation-related genes in head and neck cancers [ 14 , 15 , 16 , 17 , 18 ]. In brief, our study quantifies the global m 6 A level in HNSCC cell lines and cancerous and paired-matched histopathologically unchanged tissues and correlates its content with expression of selected RNA methylation methyltransferase (METTL3), demethylase (FTO), and m 6 A binding proteins (YTHDF2, YTHDC2).…”