Identification and Validation of a Prognostic Signature of m 5 C-Related Genes for Esophageal Cancer

Abstract

Abstract Background Esophageal cancer (ESCA) is a prevalent form of cancer with a grim prognosis. It has been reported that 5-methylcytosine (m5C) regulators are closely linked to carcinogenesis and distant metastasis. However, the role of m5C regulator in ESCA is still elusive. The aim of this study was to investigate the connections between m5C regulators and the initiation and progression of ESCA, with a particular focus on prognosis. Methods Gene expression profile data from TCGA database, including 11 normal and 142 tumor tissues, were obtained and divided into two ESCA subtypes according to the m5C regulators expression. Differentially expressed genes (DEGs) of two ESCA subtypes, normal and tumor tissues from TCGA, and normal and tumor tissues from validation datasets were analyzed. Inter-DEGs were filtered from the overlap of three sets of DEGs which named inter-DEGs. Functional analysis, immune infiltration analysis, drug sensitivity analysis, prognosis model was carried out to investigate the biological function and potential role of m5C regulators in ESCA. The expression of PLA2G2F, HHIP, TNXB, and STK31 in ESCA and adjacent esophageal tissues was detected by RT-qPCR. Results The expression of m5C regulators, namely TRDMT1, NSUN2, NSUN4, NSUN6, DNMT1, ALYREF, and YBX1, were upregulated in ESCA subtype 2 group. Correlation analysis demonstrated that m5C regulators positively correlated with E2F targets, G2M checkpoint, MYC targets V1, while negatively correlated with TNF-α signaling via NF-kB, and Notch signaling pathway. Additionally, the immune infiltration analysis indicated that m5C regulators was positively correlated with Macrophages M0, and negatively correlated with T cells CD8 infiltration. 4 independent prognostic genes, including PLA2G2F, HHIP, TNXB, and STK31, were selected to construct prognostic model and exhibited good function in predicting the prognosis of ESCA patients. RT-qPCR was used to validate the gene expression that the PLA2G2 had higher expression in ESCA tissues compared to adjacent tissues, while the expression of STK31, HHIP, and TNXB showed down regulation in ESCA tissues. Conclusions This study explored the comprehensive feature of 2 subtypes of m5C regulators in ESCA patients, which may improve understanding of m5C regulation in the tumor biology of ESCA.