title: MiR-29a is a candidate biomarker of better survival in metastatic high-grade serous carcinoma.
abstract: The objective of this study was to analyze the clinical role of 9 microRNAs (miRs) previously found to be overexpressed in ovarian carcinoma effusions compared with primary ovarian carcinomas. High-grade serous carcinoma effusions (n=148) were analyzed for expression of miR-29a, miR-31, miR-99b, miR-182, miR-210, miR-221, miR-222, miR-224, and miR-342 using quantitative polymerase chain reaction. Expression levels were analyzed for association with clinicopathological parameters and survival. miR-29a and miR-31 levels were further assessed for association with protein expression of their targets Stathmin and DNA methyltransferase-3A (DNMT3A) by immunohistochemistry and Western blotting, respectively. miRNA levels were unrelated to clinicopathological parameters. However, higher miR-29a levels were significantly related to longer overall survival in univariate (P=.007) and Cox multivariate survival analysis (P=.045). miR-29a levels were inversely related to those of its target DNMT3A (P=.048), and higher DNMT3A expression was significantly related to poor overall survival in univariate (P=.03) and Cox multivariate (P=.016) survival analysis. In contrast, miR-31 levels were directly related to cytoplasmic phospho-Stathmin expression (P=.029) and unrelated to Stathmin and nuclear phospho-Stathmin, and both Stathmin and phospho-Stathmin expressions were unrelated to survival. miR-29a and its target DNMT3A are novel candidate biomarkers of longer and shorter survival, respectively, in metastatic high-grade serous carcinoma.
authors.affiliation: Department of Pathology, Oslo University Hospital, Norwegian Radium Hospital, N-0310 Oslo, Norway.
authors.forename: Dag Andre
authors.initials: DA
authors.lastname: Nymoen
authors.affiliation: Department of Pathology, Oslo University Hospital, Norwegian Radium Hospital, N-0310 Oslo, Norway.
authors.forename: Ana
authors.initials: A
authors.lastname: Slipicevic
authors.affiliation: Department of Pathology, Oslo University Hospital, Norwegian Radium Hospital, N-0310 Oslo, Norway.
authors.forename: Arild
authors.initials: A
authors.lastname: Holth
authors.affiliation: Department of Pathology, Oslo University Hospital, Norwegian Radium Hospital, N-0310 Oslo, Norway.
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Emilsen
authors.affiliation: Department of Oncology, Oslo University Hospital, Norwegian Radium Hospital, N-0310 Oslo, Norway.
authors.forename: Thea E
authors.initials: TE
authors.lastname: Hetland Falkenthal
authors.affiliation: Department of Gynecologic Oncology, Oslo University Hospital, Norwegian Radium Hospital, N-0310 Oslo, Norway; Faculty of Medicine, Institute of Clinical Medicine, University of Oslo, N-0316 Oslo, Norway.
authors.forename: Claes G
authors.initials: CG
authors.lastname: Tropé
authors.affiliation: Institute of Drug Research, School of Pharmacy, Faculty of Medicine, The Hebrew University of Jerusalem, Jerusalem 91120, Israel.
authors.forename: Reuven
authors.initials: R
authors.lastname: Reich
authors.affiliation: Department of Pathology, Oslo University Hospital, Norwegian Radium Hospital, N-0310 Oslo, Norway.
authors.forename: Vivi Ann
authors.initials: VA
authors.lastname: Flørenes
authors.affiliation: Department of Pathology, Oslo University Hospital, Norwegian Radium Hospital, N-0310 Oslo, Norway; Faculty of Medicine, Institute of Clinical Medicine, University of Oslo, N-0316 Oslo, Norway. Electronic address: bend@medisin.uio.no.
authors.forename: Ben
authors.initials: B
authors.lastname: Davidson
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000032:analysis / Q000235:genetics*; D004248:DNA (Cytosine-5-)-Methyltransferases / Q000032:analysis; D000090205:DNA Methyltransferase 3A; D018572:Disease-Free Survival; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D020022:Genetic Predisposition to Disease; D006801:Humans; D053208:Kaplan-Meier Estimate; D035683:MicroRNAs / Q000235:genetics*; D008875:Middle Aged; D015999:Multivariate Analysis; D060787:Neoplasm Grading; D018297:Neoplasms, Cystic, Mucinous, and Serous / Q000737:chemistry / Q000235:genetics* / Q000401:mortality / Q000556:secondary; D010051:Ovarian Neoplasms / Q000737:chemistry / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D010641:Phenotype; D010766:Phosphorylation; D016016:Proportional Hazards Models; D012307:Risk Factors; D050777:Stathmin / Q000032:analysis; D013997:Time Factors; D015854:Up-Regulation
chemical_list: D014408:Biomarkers, Tumor; C000717967:DNMT3A protein, human; C532045:MIRN29a microRNA, human; D035683:MicroRNAs; C493995:STMN1 protein, human; D050777:Stathmin; D004248:DNA (Cytosine-5-)-Methyltransferases; D000090205:DNA Methyltransferase 3A
keywords: Effusions; High-grade serous carcinoma; MicroRNA; Survival; Targets