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Deregulation of miR-519a, 153, and 485-5p and its clinicopathological relevance in ovarian epithelial tumours.

Histopathology. 2010 Nov;57(5):734-43. doi:10.1111/j.1365-2559.2010.03686.x
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摘要


AIMS:The pathological and clinical significance of aberrant miRNA expression in ovarian tumours has yet to be adequately documented. The aim of this study was to assess the differences in miRNA expression of human ovarian tumours according to histological subtype, and to determine whether miRNAs are potential diagnostic and prognostic markers in ovarian cancers. METHOD AND RESULTS:The miRNA expression profiles of 103 human ovarian tumours were evaluated. Via a bead-based miRNA microarray, five aberrant miRNAs were selected which were expressed differentially in malignant serous tumours from borderline and benign ovarian tumours, including miRNA (miR)-519a, miR-18b (up-regulation) and miR-153, miR-511 and miR-485-5p (down-regulation). We conducted quantitative real-time reverse transcription-polymerase chain reaction (qRT-PCR) in order to confirm that these miRNAs are differentially expressed in different histological subtypes of ovarian tumours, and compared the expression profiles of these miRNAs between different clinical subsets. The expression of these miRNAs was correlated with clinicopathological parameters. miR-519a, miR-153 and miR-485-5p were differentially expressed in four major histotypes of ovarian cancers (P < 0.05), which suggests that they might be of potential importance as diagnostic biomarkers. Down-regulation of miR-153 and miR-485-5p was correlated significantly with FIGO grade 3 (P < 0.05). Down-regulation of miR-153 and up-regulation of miR-519a were correlated significantly with advanced clinical stage (P < 0.05). The results of Kaplan-Meier survival analysis indicated that the higher expression of miR-519a in late stage serous carcinoma was associated significantly with poor progression-free survival (P = 0.0058). CONCLUSIONS:A significant correlation was detected between the deregulation of specific types of miRNAs, such as miR-519a, miR-153 and miR-485-5p, and clinical variables as well as histological subtypes in ovarian cancers. Hence, these miRNAs may perform functions as diagnostic or prognostic biomarkers.

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