Zhao Huaying, Xu Yue, Xie Yilin, Zhang Lan, Gao Ming, Li Shenglei, Wang Feng
Department of Pathology, The First Affiliated Hospital, Zhengzhou University, Zhengzhou, China.
Department of Oncology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
Front Cell Dev Biol. 2021 Mar 4;9:650023. doi: 10.3389/fcell.2021.650023. eCollection 2021.
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甲基腺苷(m6A)RNA甲基化调节因子在肿瘤发生发展中起重要作用。然而,它们在食管癌(EC)中的功能尚未完全阐明。在此,我们分析了来自TCGA数据集的775例EC患者的24种主要m6A RNA甲基化调节因子的基因表达数据。本研究表明,m6A调节因子在基因组中的异常与人类EC的预后相关。同时,17种m6A调节因子在EC样本中表达增加,包括YTHDC1、IGF2BP2、FTO、METTL14、YTHDF3、RBM15、WTAP、HNRNPA2B1、HNRNPC、ALKBH5、YTHDF2、METTL16、IGF2BP3、VIRMA、RBM15B、YTHDF1、KIAA1429、HAKAI和ZC3H13。其中,我们发现HNRNPC、YTHDC2、WTAP、VIRMA、IGF2BP3和HNRNPA2B1与EC的较差预后和晚期显著相关。此外我们还表明,m6A调节因子的水平与EC中免疫调节因子(免疫抑制剂、免疫刺激剂和MHC分子)的表达及免疫浸润水平相关。生物信息学进一步证实,m6A调节因子参与调节RNA剪接、RNA稳定性和细胞增殖。我们的研究表明,m6A调节因子是EC癌症免疫治疗中有前景的靶点和生物标志物。