M6A Regulators Is Differently Expressed and Correlated With Immune Response of Esophageal Cancer.

Huaying Zhao,Feng Wang,Yilin Xie,Ming Gao,Shenglei Li,Yue Xu,Lan Zhang

doi:10.3389/fcell.2021.650023

Huaying Zhao, Feng Wang + Show 5 more

Open Access

https://doi.org/10.3389/fcell.2021.650023

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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.

Highlights

Esophageal cancer (EC) accounts for 1% of all cancer cases, had been the eighth most commonly diagnosed cancer (Malhotra et al, 2017; Fan et al, 2020)
We revealed higher levels of HNRNPC (Figure 4A), YTHDC2 (Figure 4B), WTAP (Figure 4C), VIRMA (Figure 4D), IGF2BP3 (Figure 4E), and HNRNPA2B1 (Figure 4F) were significantly associated with worse outcomes in esophageal cancer (EC), indicating these m6A regulators had key roles in EC
We found HNRNPC, YTHDC2, WTAP, VIRMA, IGF2BP3, and HNRNPA2B1 were significantly correlated to worse outcomes and advanced stage in EC, indicating these m6A regulators play important roles in EC and hold the key to the prognosis of patients

Summary

Introduction

Esophageal cancer (EC) accounts for 1% of all cancer cases, had been the eighth most commonly diagnosed cancer (Malhotra et al, 2017; Fan et al, 2020). ESCC is the main subtype of EC in developing countries, accounting for more than 90% of all subtypes of EC in China (Liang et al, 2017). Targeted therapy is a key step in the development of m6A Regulators in Esophageal Cancer individualized treatment for EC. Signals in immune microenvironment, including accumulation of tumor metabolites or T cell dysfunction, may significantly affect the response to immune checkpoint therapy (ICT) in EC patients (Wu et al, 2020). The development of monoclonal antibodies against programmed death 1 (PD-1) or programmed death ligand 1 (PD-L1) has achieved convincing efficacy and clinical benefits in a variety of malignant tumors including ESCC (Yuan et al, 2017; Baba et al, 2020)

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