TY - JOUR
T1 - Mir-29a is a candidate biomarker of better survival in metastatic high-grade serous carcinoma
AU - Nymoen, Dag Andre
AU - Slipicevic, Ana
AU - Holth, Arild
AU - Emilsen, Elisabeth
AU - Falkenthal, Thea E.Hetland
AU - Tropé, Claes G.
AU - Reich, Reuven
AU - Flørenes, Vivi Ann
AU - Davidson, Ben
N1 - Publisher Copyright:
© 2016 Elsevier Inc.
PY - 2016/8/1
Y1 - 2016/8/1
N2 - Summary 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.
AB - Summary 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.
KW - Effusions
KW - High-grade serous carcinoma
KW - MicroRNA
KW - Survival
KW - Targets
UR - http://www.scopus.com/inward/record.url?scp=84971325330&partnerID=8YFLogxK
U2 - 10.1016/j.humpath.2016.03.010
DO - 10.1016/j.humpath.2016.03.010
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C2 - 27063471
AN - SCOPUS:84971325330
SN - 0046-8177
VL - 54
SP - 74
EP - 81
JO - Human Pathology
JF - Human Pathology
ER -