Candidate microRNA biomarkers in human epithelial ovarian cancer: systematic review profiling studies and experimental validation

Abstract

Despite advances in detection and therapy, epithelial ovarian cancer (EOC) still represents the most lethal gynecologic malignancy in women worldwide. The high mortality of EOC is mainly due to late-stage diagnosis for more than 70% of patients. There is an urgent need to search for specific and sensitive biomarkers for early diagnosis of EOC. Recently, the cumulative data indicated an essential role for microRNA (miRNA), a class of small non-coding RNAs targeting multiple mRNAs and triggering translation repression and/or RNA degradation, in ovarian caner carcinogenesis and progression. Here, we reviewed the published miRNA expression profiling studies that compared the miRNA expression profiles between EOC tissues or cell lines and normal ovarian tissues or benign ovarian tumor or human primary cultured ovarian surface epithelial cells. A miRNA ranking system that takes the number of comparisons in agreement and direction of differential expression into the consideration was devised and used. Finally, five promising differentially miRNAs (miR-200a, miR-100, miR-141, miR-200b, and miR-200c) were reported with the consistent direction in four or more studies. MiR-200a, miR-200b, miR-200c, and miR-141, all of them belong to miR-200 family, were reported with consistently up-regulated in at least 4 studies, whereas miR-100 was reported with down-regulated in 4 studies. Furthermore, we validated these miRNAs in a clinical setting using qRT-PCR and their dysregulations in EOC tissues confirmed the findings. Conclusively, the five most consistently expressed miRNAs might provide some clues of the potential biomarkers in EOC. Further mechanistic and precise validation studies are needed for their clinical significances and roles in the progression of EOC.