Abstract
BackgroundOvarian cancer is the most fatal tumor of the female reproductive system and the fifth leading cause of cancer death among women in the USA. The prognosis is poor due to the lack of biomarkers for treatment options.ResultsThe methylation array data of 551 patients with ovarian serous cystadenocarcinoma (OSC) in The Cancer Genome Atlas (TCGA) database were assessed in this study to explore the methylation biomarkers associated with prognosis and improve the prognosis of patients. These patients were divided into training (first two thirds) and validation datasets (remaining one third). A five-DNA methylation signature was found to be significantly associated with the overall survival of patients with OSC using the Cox regression analysis in the training dataset. The Kaplan–Meier analysis showed that the five-DNA methylation signature could significantly distinguish the high- and low-risk patients in both training and validation sets. The receiver operating characteristic (ROC) analysis further confirmed that the five-DNA methylation signature exhibited high sensitivity and specificity to predict the prognostic survival of patients. Also, the five-DNA methylation signature was not only applicable in patients of different ages, stages, histologic grade, and size of residual tumor after surgery but also more accurate in predicting OSC prognosis compared with known biomarkers.ConclusionsThis five-DNA methylation signature demonstrated the potential of being a novel independent prognostic indicator and served as an important tool for guiding the clinical treatment of OSC to improve outcome prediction and management for patients. Hence, the findings of this study might have potential clinical significance.
Highlights
Ovarian cancer is the most fatal tumor of the female reproductive system and the fifth leading cause of cancer death among women in the USA
DNA methylation is well known to be associated with ovarian cancer and has great potential to serve as a biomarker in screening the disease, monitoring response to therapy, and predicting the prognosis [5, 6]
Patients with higher methylation levels of ABCA1 have shorter overall survival [10]; hypomethylation of CpG sites within the MSX1 gene is associated with resistant high-grade serous ovarian cancer [15]; and OPCML gene promoter methylation can serve as a useful biomarker for predicting the prognosis of patients with ovarian cancer [5]
Summary
Ovarian cancer is the most fatal tumor of the female reproductive system and the fifth leading cause of cancer death among women in the USA. DNA methylation is well known to be associated with ovarian cancer and has great potential to serve as a biomarker in screening the disease, monitoring response to therapy, and predicting the prognosis [5, 6]. Patients with higher methylation levels of ABCA1 have shorter overall survival [10]; hypomethylation of CpG sites within the MSX1 gene is associated with resistant high-grade serous ovarian cancer [15]; and OPCML gene promoter methylation can serve as a useful biomarker for predicting the prognosis of patients with ovarian cancer [5]. The reproducibility of prognostic methylation signature identified is limited by different specimens and the lack of adjustment for major confounding factors [16]
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