Abstract

MicroRNAs (miRNAs) have been found to be dysregulated in epithelial ovarian cancer (EOC) and may function as either tumor suppressor genes (TSGs) or as oncogenes. Hypermethylation of miRNA silences the tumour suppressive function of a miRNA or hypermethylation of a TSG regulating that miRNA (or vice versa) leads to its loss of function. The present study aims to evaluate the impact of aberrant microRNA-125b (miR-125b) expression on various clinicopathological features in epithelial ovarian cancer and its association with anomalous methylation of several TSGs. We enrolled 70 newly diagnosed cases of epithelial ovarian cancer, recorded their clinical history and 70 healthy female volunteers. Serum miR-125b levels were determined by quantitative reverse transcription polymerase chain reaction (qRT-PCR) and the methylation status of various TSGs was investigated by methylation specific PCR. ROC curves were constructed to estimate the diagnostic and prognostic usefulness of miR-125b. The Kaplan—Meier method was applied to compare survival curves. Expression of miR-125b was found to be significantly upregulated (p<0.0001) in comparison with healthy controls. The expression level of miR-125b was found to be significantly associated with FIGO stage, lymph node and distant metastasis. ROC curve for diagnostic potential yielded significant AUC with an equitable sensitivity and specificity. ROC curves for prognosis yielded significant AUCs for histological grade, distal metastasis, lymph node status and survival. The expression of miR-125b also correlated significantly with the hypermethylation of TSGs. Our results indicate that DNA hypermethylation may be involved in the inactivation of miR-125b and miR-125b may function as a potential independent biomarker for clinical outcome in EOC.

Highlights

  • Ovarian cancer is the leading cause of cancer related deaths worldwide

  • The present study aims to evaluate the impact of aberrant microRNA-125b expression on various clinicopathological features in epithelial ovarian cancer and its association with anomalous methylation of several tumor suppressor genes (TSGs)

  • Serum miR-125b levels were determined by quantitative reverse transcription polymerase chain reaction and the methylation status of various TSGs was investigated by methylation specific PCR

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Summary

Introduction

Ovarian cancer is the leading cause of cancer related deaths worldwide. The high rate of mortality may be due to difficulties in diagnosing it at an early stage and lack of effective treatments for patients with an advanced or recurrent disease[1]. Taking into account the important regulatory roles miRNA play in cancer development and progression, several studies have been conducted to identify miRNA as potential biomarkers for cancer diagnosis, prognosis and personalized therapy[3]. Aberrant miRNA expression has been frequently observed in various types of human tumors. Recent studies reported dysregulation of miR-125b in various cancers[5,6]. The mechanism by which miR-125b contributes to epithelial ovarian cancer (EOC) has not been documented and is still relatively unclear. High expression of miR-125 had been observed in gliomas and prostate cancer[7,8] while miR-125 levels were seen to decrease in breast and gastric cancer[9,10]. The expression level of miR-125b in epithelial ovarian cancer is not clear yet. As per the putative promoter region, the promoter of miR-125b is embedded in CpG island[11]

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