Utility of Serum miR-125b as a Diagnostic and Prognostic Indicator and Its Alliance with a Panel of Tumor Suppressor Genes in Epithelial Ovarian Cancer

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.

A Pilot Study of Circulating MicroRNA-125b as a Diagnostic and Prognostic Biomarker for Epithelial Ovarian Cancer

“…In addition, expression level of serum miR-125b was found to be significantly lower in late stages (III and IV) than early stages (I and II). Patients with lymph node and distant metastasis showed significantly lower serum miRNA levels 28. Our data were in consistence to their findings.…”

“…Our data were in consistence to their findings. However, possibly due to smaller sample size and shorter follow-up period, serum miRNA-125b levels were not significantly associated with OS in their study 28. These data imply that miRNA-125b may play an important role in ovarian carcinogenesis and that it might play a different role as cancer progresses.…”

Circulating biomarkers in epithelial ovarian cancer diagnosis: from present to future perspective

“…Zuberi et al documented the high expression of miR125b in serum of OC women and reported for miR-125b an AUC of 0.73 (95% CI: 0.64-0.81) to discriminate patients with malignant OC from healthy controls. At the best cutoff, the sensitivity and specificity were 62.3% and 77.1%, respectively (104).…”

MicroRNA‐125b as a tumor suppressor by targeting MMP11 in breast cancer

“…Therefore, a microRNA has many downstream target genes that can cause extensive protein changes, thereby inducing or suppressing the occurrence or development of tumor. A large number of studies have shown that miRNA‐125b is significantly increased in tumor tissues of oral and endometrial cancers, and can promote tumor cell proliferation through various pathways . MicroRNA, as a population with significant abnormal expression, regulates mRNA expression mainly at the post‐transcriptional level.…”