Identification and validation of a prognostic signature of mC-related genes for esophageal cancer.

BACKGROUND

Esophageal cancer (ESCA) is one of the most common malignancies, and has a poor prognosis. The role of 5-methylcytosine (mC) regulators has been linked to carcinogenesis in a number of cancers. However, the role of mC regulators in ESCA is unclear. This study sought to examine the relationships between mC regulators and the tumorigenesis of ESCA.

METHODS

Based on the expression of the mC regulators in 11 normal tissue and 142 tumor tissue samples from The Cancer Genome Atlas (TCGA) database, two ESCA subtypes were identified. The two ESCA subtypes, normal and tumor tissue samples from TCGA, and normal and tumor tissue samples from validation datasets were analyzed to identify the differentially expressed genes (DEGs). To investigate the biological function of the mC regulators in ESCA, a functional analysis was conducted, and a prognostic model was established. Using reverse transcription-quantitative polymerase chain reaction (RT-qPCR), , , and expression was detected in the ESCA and adjacent esophageal tissues.

RESULTS

The mC regulators, including , , , , , , and , were upregulated in the ESCA subtype 2 group. Further, the gene set variation analysis (GSVA) and correlation analysis revealed that the mC regulators were positively correlated with the promoter-binding factor () transcription factor 1 targets and the G2 phase to M phase checkpoint (G2M), and were negatively correlated with tumor necrosis factor-signaling via nuclear factor kappa beta pathways. Four independent prognostic genes (i.e., , , and ) were selected to construct a model to predict the prognosis of ESCA patients. According to the RT-qPCR analysis, expression was higher in the ESCA tissues than the adjacent tissues, while , , and expression was lower.

CONCLUSIONS

Two subtypes of mC regulators in ESCA patients were explored. Our findings may improve the understanding of mC regulators in the biology of ESCA.