HPV-Related Promoter Methylation-Based Gene Signature Predicts Clinical Prognosis of Patients With Cervical Cancer

Abstract

Persistent high-risk HPV infection drives tumorigenesis in various human malignancies, including cervical, oropharyngeal, anal, and vulvar carcinomas. Although HPV-related tumors arise in several different sites, they share many common genetic and epigenetic events. Complex and heterogeneous genomic aberrations and mutations induced by high-risk HPV contribute to the initiation and progression of cervical cancer (CC). However, the associations between high-risk HPV infection and DNA methylation have not been clearly investigated. In the present study, HPV-related gene promoter methylation signature was comprehensively analyzed using multiple interactive platforms. CC patients were successfully classified into high-risk and low-risk groups with significant differences in clinical outcomes based on the HPV-related gene promoter methylation signature. Moreover, the protein levels of ALDH1A2 and clinical prognostic value were confirmed in the CC patients cohort. In summary, our study provides compelling evidence that HPV-related gene promoter methylation signature serves as a strong prognostic signature for CC patients. Clinical investigations in large CC patient cohorts are greatly needed to pave the way to implement epigenetic biomarkers into better clinical management.