The online version of this article (doi:10.1186/1477-7819-10-174) contains supplementary material, which is available to authorized users.
The authors have no commercial or other associations that might pose a conflict of interest.
HL, CP, GD, and JM conducted the experiments and HL drafted the manuscript. JS analyzed the data and SH assisted in the manuscript preparation. ES provided HOSE cell lines and assisted during the experiments and in the manuscript preparation. NK and QF conceptualized, edited, and revised the manuscript. All authors have read and approved the final manuscript.
MicroRNA (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.
We 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.
Expression 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.
Aberrant 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.
Additional file 1: miRNA expression in HOSE cell lines, normal ovaries, and benign ovarian tumors. Expression of miR-181d, miR-368, and miR-370 was significantly different between cell lines and normal ovaries as well as between cell lines and benign tumors. In addition, expression of miR-30c and miR-30e-3p was significantly different between cell lines and normal ovaries, and expression of miR-30c was significantly different between normal ovaries and benign tumors. (PDF 49 kb) (PDF 50 KB)12957_2012_1049_MOESM1_ESM.pdf
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- MicroRNA expression in ovarian carcinoma and its correlation with clinicopathological features
Chul Soo Park
Joshua E Stern
Stephen E Hawes
Nancy B Kiviat
- BioMed Central
Neu im Fachgebiet Chirurgie
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