MicroRNA expression in ovarian carcinoma and its correlation with clinicopathological features

Abstract

BackgroundMicroRNA (miRNA) expression is known to be deregulated in ovarian carcinomas. However, limited data is available about the miRNA expression pattern for the benign or borderline ovarian tumors as well as differential miRNA expression pattern associated with histological types, grades or clinical stages in ovarian carcinomas. We defined patterns of microRNA expression in tissues from normal, benign, borderline, and malignant ovarian tumors and explored the relationship between frequently deregulated miRNAs and clinicopathologic findings, response to therapy, survival, and association with Her-2/neu status in ovarian carcinomas.MethodsWe measured the expression of nine miRNAs (miR-181d, miR-30a-3p, miR-30c, miR-30d, miR-30e-3p, miR-368, miR-370, miR-493-5p, miR-532-5p) in 171 formalin-fixed, paraffin-embedded ovarian tissue blocks as well as six normal human ovarian surface epithelial (HOSE) cell lines using Taqman-based real-time PCR assays. Her-2/neu overexpression was assessed in ovarian carcinomas (n = 109 cases) by immunohistochemistry analysis.ResultsExpression of four miRNAs (miR-30c, miR-30d, miR-30e-3p, miR-370) was significantly different between carcinomas and benign ovarian tissues as well as between carcinoma and borderline tissues. An additional three miRNAs (miR-181d, miR-30a-3p, miR-532-5p) were significantly different between borderline and carcinoma tissues. Expression of miR-532-5p was significantly lower in borderline than in benign tissues. Among ovarian carcinomas, expression of four miRNAs (miR-30a-3p, miR-30c, miR-30d, miR-30e-3p) was lowest in mucinous and highest in clear cell samples. Expression of miR-30a-3p was higher in well-differentiated compared to poorly differentiated tumors (P = 0.02), and expression of miR-370 was higher in stage I/II compared to stage III/IV samples (P = 0.03). In multivariate analyses, higher expression of miR-181d, miR-30c, miR-30d, and miR-30e-3p was associated with significantly better disease-free or overall survival. Finally, lower expression of miR-30c, miR-30d, miR-30e-3p and miR-532-5p was significantly associated with overexpression of Her-2/neu.ConclusionsAberrant expression of miRNAs is common in ovarian tumor suggesting involvement of miRNA in ovarian tumorigenesis. They are associated with histology, clinical stage, survival and oncogene expression in ovarian carcinoma.

Expression of miR-146a in patients with ovarian cancer and its clinical significance

“…First, only tumors of serous histology were included in the present study and tumors of different origin may exhibit different patterns of miRNA expression. Previous profiling studies that included different histological types of ovarian cancer support this observation and reported different miRNA expression in serous, mucinous, endometrial and clear-cell types of cancer (33), as well as in borderline and invasive tumors (19). It has also been demonstrated that miR-146a expression was downregulated in highly metastatic breast cancer.…”

“…The level of miR-370 expression was increased in FIGO stage I/II samples compared with FIGO stage III/IV tissue samples. Additionally, upregulated expression of miR-181d, miR-30c, miR-30d and miR-30e-3p significantly improved disease-free survival or OS (19). To the best of our knowledge, miR-146a expression has not been associated with clinical outcomes of ovarian cancer.…”

“…The expression of miR-30a-3p was increased in well-differentiated tumors compared with poorly differentiated tumors (19). Detection of high levels of plasma miR-205 and low Let-7f expression levels combined with high serum cancer antigen 125 (CA125) levels improved the accuracy of ovarian cancer detection (20).…”

Low expression of microRNA-30c promotes prostate cancer cells invasion involved in downregulation of KRAS protein

“…Lee et al (15) previously reported that mir-30c had significantly lower expression in ovarian cancer tissue compared with normal ovarian tissue, and additional multivariate analysis revealed that patients with ovarian cancer mir-30c high expression had longer survival and overall survival rate. Zhou et al (16) revealed that miR-30c is a tumor suppressor gene that can inhibit the growth of endometrial cancer by targeting the expression of metastasis-associated 1.…”

Recent findings on epigenetic gene abnormalities involved in uterine cancer

“…Zhou et al demonstrated that miR-30c overexpression inhibited metastasis-associated gene-1 (MTA1) (59). miR-30c is decreased in endometrial, ovarian, breast and gastric cancer (60)(61)(62)(63) and it is involved in carcinogenesis through its association with MTA1.…”