MiRNA-200a/c as potential biomarker in epithelial ovarian cancer (EOC): evidence based on miRNA meta-signature and clinical investigations.

Yue Teng,Xuan Su,Wenquan Niu,Kai Qu,Yan Zhang,Chen Li,Xing Zhang,Chang Liu

doi:10.18632/oncotarget.13154

Abstract

Extensive effort has been put on miRNA expression signatures in epithelial ovarian cancer (EOC). Unfortunately, consistent conclusion rarely yielded from diverse studies, mainly due to the high inter-lab variability and small sample sizes. To overcome above limitations, an integrated analysis of miRNA expression signature was performed by employing Robust Rank Aggregation (RRA) method. Diagnostic analysis, Kaplan-Meier survival curves and pathway enrichment analysis were used to investigate the clinical values and biological functions of meta-signature miRNAs. A total of 519 EOC and 248 noncancerous samples were included. Seven mostly dysregulated miRNAs were identified by RRA method and two miRNAs (miR-200a-3p and miR-200c-3p) remained statistically significant after Bonferroni-correction. Diagnostic meta-analysis showed reliable diagnostic capacity of miR-200a-3p (with a pooled sensitivity of 0.84 and specificity of 0.83) and miR-200c-3p (with a pooled sensitivity of 0.75 and specificity of 0.66) for EOC. Pathway enrichment analysis and expression correlation analysis suggested miR-200a/c might contribute EOC progression by affecting cellular adhesion process. Kaplan-Meier survival analysis based on two independent cohorts revealed a strong association between miR-200a/c and overall survival in EOC patients. miR-200a/c was identified as the mostly dysregulated miRNAs in EOC and might be novel diagnostic and prognostic biomarkers for patients with EOC.

Highlights

Epithelial ovarian cancer (EOC) accounts for 25% of all malignancies affecting the female genital tract and is the most lethal gynecological malignancy, accounting for 4.2 % of all cancer-related deaths in women
According to the search criteria, a total of 14 independent full-text studies retrieved from public databases were used to build the epithelial ovarian cancer (EOC) miRNA expression profiling datasets [17,18,19,20,21,22,23,24,25,26,27,28,29]
When employing the miRPath algorithm to calculate the combinatorial effect of miR200a-3p and miR-200c-3p in cellular pathway, our results showed that miR-200a/c might affect cellular adhesionrelated pathways (KEGG_04520 Adherens junction with a false discovery rate (FDR) of 5.76E-07; KEGG_04510 Focal adhesion with a FDR of 1.40E-02) (Figure 5A and Supplementary Table S2)

Summary

Introduction

Epithelial ovarian cancer (EOC) accounts for 25% of all malignancies affecting the female genital tract and is the most lethal gynecological malignancy, accounting for 4.2 % of all cancer-related deaths in women. Most EOC patients are diagnosed at late stages, leaving little chance for survival due to the lack of effective treatments [1, 2]. Incidence of EOC has been slowly yet steadily increasing, while development of more effective treatment has lagged behind, leading to little, if not none, improvement in overall survival. Most EOC patients recur after a few years and turn to be resistant to existing treatments [3, 4]. Despite the use of aggressive treatment, recurrence is frequently seen among EOC patients, and cancerous metastasis is one of the predominant causes www.impactjournals.com/oncotarget of mortality. Exploration of novel biomarkers for early diagnosis, prognosis prediction, and effective therapies will definitely contribute to current EOC treatment and management

Methods

Results

Conclusion