Methylation of OPCML promoter in ovarian cancer tissues predicts poor patient survival

Abstract

BACKGROUND: Ovarian cancer is a lethal gynecological malignancy largely due to the lack of biomarkers for early detection and treatment options. Opioid binding protein/cell adhesion molecule-like gene (OPCML) has a tumor-suppressor function in ovarian cancer, and epigenetic inactivation of OPCML induces oncogenic transformation of human ovarian surface epithelial cells. METHODS: This study investigated OPCML promoter methylation levels in ovarian cancer tissues. A total of 30 normal ovarian, 85 benign ovarian tumor, and 102 ovarian cancer tissues were subjected to quantitative methylation-specific PCR analysis of OPCML methylation. Four ovarian cancer cell lines were cultured and treated with the DNA demethylation agent 5-aza-2'-deoxycytidine (5-AZA) for restoring OPCML expression. RESULTS: The data showed that 80 of 102 (78.4%) ovarian cancer tissues and 28 of 85 (32.9%) benign ovarian tumors had a methylated OPCML gene promoter. In contrast, there was no OPCML gene promoter methylation in any of the 30 normal ovarian samples. OPCML promoter methylation was significantly associated with an older age of the patients (p=0.022), an advanced pathological stage of ovarian cancer (p=0.023), and poor overall survival of ovarian cancer patients (p<0.001). Multivariate analysis data showed that pathological stage, age, and OPCML promoter methylation were all independent factors to predict overall survival of patients. Furthermore, 5-AZA was able to restore expression of OPCML mRNA and protein in ovarian cancer cell lines. CONCLUSIONS: These data indicate that detection of OPCML gene promoter methylation could be a useful biomarker for predicting the prognosis of ovarian cancer patients and disease progression.