title: MicroRNA let-7a modifies the effect of self-renewal gene HIWI on patient survival of epithelial ovarian cancer.
abstract: Aberrant expressions of self-renewal gene HIWI and microRNA (miRNA) let-7a are observed in epithelial ovarian cancer (EOC). A U-shape association between HIWI expression and overall survival is seen in several human cancers but unknown in EOC. HIWI directly and/or indirectly interacts with let-7a, but the clinical relevance of this interaction is yet to be addressed. Here, we analyzed HIWI and let-7a expressions in 211 primary EOC tissues using quantitative reverse-transcription PCR to investigate HIWI and its interaction with let-7a in the prognostic significance of EOC. Associations of HIWI and its interaction with miRNA let-7a with patient survival were analyzed using the Kaplan-Meier survival curves and Cox proportional hazard regression models. Kaplan-Meier survival curves showed that patients with medium HIWI had poorer overall survival than those with low or high HIWI. An 89% increased death risk (HR = 1.89, 95% CI: 1.29-2.98) was observed in the medium HIWI group in multivariate Cox proportional hazard regression analyses. Among patients with high let-7a expression, those with medium HIWI had an increased risk of death compared to those with low HIWI (HR = 2.62, 95% CI: 1.30-5.30), whereas among those with low let-7a, no significant association between HIWI expression and overall survival was observed (HR = 1.63, 95% CI: 0.86-3.08). Moreover, HIWI expression also affected chemotherapy response. The results suggested that miRNA let-7a could modify the effect of HIWI expression on patient survival of EOC, expanding our understanding of the clinical relevance of HIWI and let-7a interaction in EOC prognosis. © 2015 Wiley Periodicals, Inc.
authors: Department of Chronic Disease Epidemiology, Yale School of Public Health, School of Medicine, Yale Cancer Center, Yale University, New Haven, Connecticut.
authors: Lingeng
authors: L
authors: Lu
authors: Department of Surgical Science, A O Città della Salute e della Scienza di Torino, S. Anna Hospital, Turin, Italy.
authors: Dionyssios
authors: D
authors: Katsaros
authors: Department of Chronic Disease Epidemiology, Yale School of Public Health, School of Medicine, Yale Cancer Center, Yale University, New Haven, Connecticut.
authors: Harvey A
authors: HA
authors: Risch
authors: Department of Surgical Science, A O Città della Salute e della Scienza di Torino, S. Anna Hospital, Turin, Italy.
authors: Emilie Marion
authors: EM
authors: Canuto
authors: Department of Surgical Science, Division of Obstetrics and Gynecology, University of Torino School of Medicine, Mauriziano Hospital, Turin, Italy.
authors: Nicoletta
authors: N
authors: Biglia
authors: Department of Chronic Disease Epidemiology, Yale School of Public Health, School of Medicine, Yale Cancer Center, Yale University, New Haven, Connecticut.|Cancer Epidemiology Program, University of Hawaii Cancer Center, Honolulu, Hawaii.
authors: Herbert
authors: H
authors: Yu
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D060565:Argonaute Proteins / Q000235:genetics*; D000077216:Carcinoma, Ovarian Epithelial; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D053208:Kaplan-Meier Estimate; D035683:MicroRNAs / Q000235:genetics*; D008875:Middle Aged; D009375:Neoplasms, Glandular and Epithelial / Q000175:diagnosis* / Q000235:genetics* / Q000473:pathology; D010051:Ovarian Neoplasms / Q000175:diagnosis* / Q000235:genetics* / Q000473:pathology; D010053:Ovary / Q000378:metabolism / Q000473:pathology*; D011379:Prognosis
chemical_list: D060565:Argonaute Proteins; D035683:MicroRNAs; C421088:PIWIL1 protein, human; C487931:mirnlet7 microRNA, human
keywords: epithelial ovarian cancer; let-7a; piwi-like RNA-mediated gene silencing 1 (PIWIL1 or HIWI); prognosis