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MiR‐221 and MiR‐222 alterations in sporadic ovarian carcinoma: Relationship to CDKN1B, CDKNIC and overall survival
Author(s) -
Wurz Kaitlyn,
Garcia Rochelle L.,
Goff Barbara A.,
Mitchell Patrick S.,
Lee Jun Haeng,
Tewari Muneesh,
Swisher Elizabeth M.
Publication year - 2010
Publication title -
genes, chromosomes and cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.754
H-Index - 119
eISSN - 1098-2264
pISSN - 1045-2257
DOI - 10.1002/gcc.20768
Subject(s) - microrna , epigenetics , biology , immunohistochemistry , somatic cell , cancer research , methylation , cell cycle , ovarian carcinoma , oncology , ovarian cancer , medicine , cancer , gene , genetics , immunology
MicroRNAs are often aberrantly expressed in human neoplasms and are postulated to play a role in neoplastic initiation and progression. miR‐221 and miR‐222 negatively regulate expression of CDKN1B (p27) and CDKN1C (p57), two cell cycle regulators expressed in ovarian surface epithelium and down‐regulated in ovarian carcinomas. We characterized miR‐221 and miR‐222 expression in 49 sporadic high grade ovarian carcinomas and determined whether somatic mutation or epigenetic alterations explained the differences in expression of these miRNAs. We correlated these findings with protein expression of CDKN1B and CDKN1C as assessed by immunohistochemistry. Expression of miR‐221 and miR‐222 were closely correlated with each other ( P = 0.0001). Interestingly, a lower ratio of miR‐221 to miR‐222 expression was significantly correlated with worse overall survival ( P = 0.01) and remained a significant predictor of overall survival in multivariate analysis using the covariate adequacy of surgical cytoreduction ( P = 0.03). Higher miR‐222 and miR‐221 expression were significantly associated with decreased CDKN1C expression ( P = 0.009 and 0.01). In contrast, CDKN1B expression was not associated with miR‐221 or miR‐222 expression. Neither somatic mutations nor methylation of the studied region explained the alterations in miR‐221 and miR‐222 expression in most carcinomas. © 2010 Wiley‐Liss, Inc.