A ten-gene methylation signature as a novel biomarker for improving prediction of prognosis and indicating gene targets in endometrial cancer

Abstract

Endometrial cancer (EC) is a common female reproductive tumor worldwide. Nonetheless, the pathogenesis of EC still remains ambiguous and associated epigenetic mechanism still to be explored. The goal of this study is to investigate whether gene methylation signature is associated with overall survival (OS) for EC patients. In this study, a 10-gene methylation risk model was built and the OS in high- and low-risk groups was significant different. The area under the ROC curve (AUC) of this model was 0.856 at 5 years survival. The nomogram could accurately predict the OS in EC patients, with concordance index and AUC at 5 year survival reached 0.796 and 0.792, respectively. Furthermore, we verified the nomogram with 24 patients in our center and the Kaplan-Meier survival curve also proved to be significantly different (p < 0.01). WGCNA revealed a key gene group for the model and further bioinformatics analysis indicated 6 genes as the hub genes in the module. Knockdown of MMP12 inhibited the proliferation, invasion and metastasis of EC cells. After all, a methylation signature and a nomogram based on this signature were constructed, and they could both predict survival in patients with EC. Moreover, WGCNA model identified MMP12 as a potential target for the treatment of EC.