ZNF671 DNA methylation as a molecular predictor for the early recurrence of serous ovarian cancer

Abstract

Serous ovarian cancer is the most frequent type of epithelial ovarian cancer. Despite the use of surgery and platinum‐based chemotherapy, many patients suffer from recurrence within 6 months, termed platinum resistance. Currently, the lack of relevant molecular biomarkers for the prediction of the early recurrence of serous ovarian cancers is linked to the poor prognosis. To identify an effective biomarker for early recurrence, we analyzed the genome‐wide DNA methylation status characteristic of early recurrence after treatment. The patients in The Cancer Genome Atlas (TCGA) dataset who showed a complete response after the first therapy were categorized into 2 groups: early recurrence serous ovarian cancer (ERS, recurrence ≤12 months, n = 51) and late recurrence serous ovarian cancer (LRS, recurrence >12 months, n = 158). Among the 12 differently methylated probes identified between the 2 groups, we found that ZNF671 was the most significantly methylated gene in the early recurrence group. A validation cohort of 78 serous ovarian cancers showed that patients with ZNF671 DNA methylation had a worse prognosis (P < .05). The multivariate analysis revealed that the methylation status of ZNF671 was an independent factor for predicting the recurrence of serous ovarian cancer patients both in the TCGA dataset and our cohort (P = .049 and P = .021, respectively). Functional analysis revealed that the depletion of ZNF671 expression conferred a more migratory and invasive phenotype to the ovarian cancer cells. Our data indicate that ZNF671 functions as a tumor suppressor in ovarian cancer and that the DNA methylation status of ZNF671 might be an effective biomarker for the recurrence of serous ovarian cancer after platinum‐based adjuvant chemotherapy.

Epigenetic Biomarkers in the Management of Ovarian Cancer: Current Prospectives

“…This might offer utility in improving survival outcomes of patients with ovarian cancer (Fang et al, 2018). Another recent study has highlighted the tumor suppressor role of ZNF671 and its methylation could act as a predictor for early recurrence of serous ovarian carcinoma (Mase et al, 2019). Another important study by M. Keita et al has for the first time reported the exclusive association of massive DNA hypomethylation with poorly differentiated tumors, which correlates with disease aggressiveness and progression.…”

Integrated analysis of DNA methylation and mRNA expression profiles to identify key genes in head and neck squamous cell carcinoma

“…Furthermore, multiple genes were validated to be mediated by aberrant DNA methylation, acting as diagnostic, treatment, and prognostic markers for esophageal squamous carcinoma [16]. Also, the methylation status of ZNF671 was utilized as an independent marker for predicting ovarian cancer recurrence [20]. As with these different kinds of tumors, a series of methylation-related gene dysregulation has been detected in HNSCC, including p16, CDH1, DAPK and MGMT [21], implying their potential functions in HNSCC pathogenesis.…”

Development and validation of a DNA methylation signature to predict the progression-free survival in patients with advanced-stage ovarian cancer

“…Numerous studies have reported that DNA methylation can be a promising biomarker in cancer. DNA methylation of NKD1, RUNX3, and ZNF671 were reported to be predictors of progression-free survival (PFS) in patients with OC [9][10][11]. Furthermore, a previous study reported that a DNA methylation signature can predict overall survival in patients with OC [12].…”