Ascites-Derived Extracellular microRNAs as Potential Biomarkers for Ovarian Cancer

Abstract

Ovarian cancer as the most fatal gynecological malignancy is often manifested by excessive fluid accumulation known as ascites or effusion. Ascites-derived microRNAs (miRNAs) may be closely associated with ovarian cancer progression. However, our knowledge of their roles, altered expression, and clinical outcomes remained limited. In this study, large-scale expression profiling of 754 human miRNAs was performed using real-time quantitative polymerase chain reaction and 384-well TaqMan array human miRNA A and B cards to identify differentially expressed miRNAs between extracellular fraction of the ascitic fluid associated with high-grade serous ovarian carcinomas and control plasma. Of the 754 miRNAs, 153 were significantly differentially expressed relative to the controls. Expression of 7 individual miRNAs (miR-200a, miR-200b, miR-200c, miR-141, miR-429, miR-1290, and miR-30a-5p) was further validated in extended sample sets, including serous, endometrioid, and mucinous subtypes. All miR-200 family members and miR-1290 were conspicuously overexpressed, while miR-30a-5p was only weakly overexpressed. The ability of miRNAs expression to discriminate the pathological samples from the controls was strong. Receiver operating characteristic curve analyses found area under the curve (AUC) values of 1.000 for miR-200a, miR-200c, miR-141, miR-429, and miR-1290 and of AUC 0.996 and 0.885 for miR-200b and miR-30a-5p, respectively. Preliminary survival analyses indicated low expression level of miR-200b as significantly related to longer overall survival (hazard ratio [HR]: 0.25, mean survival 44 months), while high expression level was related to poor overall survival (HR: 4.04, mean survival 24 months). Our findings suggested that ascites-derived miRNAs should be further explored and evaluated as potential diagnostic and prognostic biomarkers for ovarian cancer.

Comprehensive analysis of mRNAs and miRNAs in the ovarian follicles of uniparous and multiple goats at estrus phase

“…Of these 14 highly expressed DEmiRNAs, miR-200a, miR-141, miR-1, miR-206, miR-133b, miR-133a-3p, miR-182, and miR-122 have been reported to play important roles in basic reproductive activities. miR-200a was frequently overexpressed and is closely related to the migratory, proliferative, and invasive abilities of OC cells [80][81][82]. miR-141 was shown to be significantly upregulated in OC cell lines and advanced metastatic OC [83,84], and can inhibit GC apoptosis by targeting DAPK1 through the MAPK signaling pathway, leading to the development of polycystic ovary syndrome (PCOS) [85].…”

Prognostic Values and Prospective Pathway Signaling of miR-30a in Ovarian Cancer: A Study Based on Gene Expression Omnibus and Bioinformatics Analysis

“…Subsequently, several other studies also supported the conclusion that the expression of miR-30a was upregulated in ovarian cancer tissues (14,16). Interestingly, the study of, Wang et al (15) showed that the expression level of miR-30a in poorly differentiated ovarian papillary serous carcinoma tissues was significantly higher than that in well differentiated ovarian papillary serous carcinoma tissues.…”

Bioinformatics Analysis of Prognostic value and prospective Pathway signal of miR-30a in Ovarian Cancer

“…Some studies showed that miR-30a expression was up-regulated in the tissues of ovarian cancer (14,16). Interestingly, the study of, Wang et al (15) showed that the level of miR-30a expression in poorly differentiated ovarian papillary serous carcinoma tissues was obviously higher than that in well differentiated ovarian papillary serous carcinoma tissues.…”