Clinical significance of promoter hypermethylation of genes in ovarian cancer

Abstract

// Xinxin Zhu 1, 2 and Jinghe Lang 1 1 Department of Obstetrics and Gynecology, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, China 2 Department of Obstetrics and Gynecology, Institute for Wound Research, University of Florida, Gainesville, Florida, USA Correspondence to: Jinghe Lang, email: langjh@hotmail.com , doctorlangjh@163.com Keywords: epigenetic; DNA methylation; gene silencing; immunotherapy; ovarian cancer Received: August 02, 2017      Accepted: December 18, 2017      Published: December 29, 2017 ABSTRACT Ovarian cancer is the most lethal condition in gynecologic oncology. The known prognostic factors for ovarian cancer include tumor stage, histological grade, lymph node, and distant metastasis; however, handy and reliable molecular biomarkers for prevention, diagnosis, personalized treatment, and prognosis are scarce. Despite histological differences, the clinical treatment strategy is similar for ovarian cancers. The survival rate for ovarian cancer, however, remains relatively low. Accumulating evidence suggests that hypermethylated promoters of genes can be promising candidates as molecular biomarkers in ovarian cancer risk evaluation, early detection, personalized treatment, and prognosis. With advancements in immunology, hypermethylation of gene promoters was found to alter the tumor immune microenvironment, and gene methyltransferase inhibitors can contribute to ovarian cancer immunotherapy by boosting tumor immunogenicity and immune response and decreasing immunosuppression. Although DNMTis demonstrate high efficacy in hematologic malignancies, the application of DNMTis in solid tumors is just in its beginning. This article, drawing on both preclinical and clinical data, systematically reviews the common hypermethylated genes in ovarian cancer and their clinical applications, evaluating their usefulness in early diagnosis, personalized treatment, prognosis prediction, and the establishment of combined therapy of methyltransferase inhibitors and immunotherapy.