title: LIN-28B/let-7a/IGF-II axis molecular subtypes are associated with epithelial ovarian cancer prognosis.
abstract: OBJECTIVE
  Aberrant expressions of LIN-28B, let-7a and IGF-II occur in epithelial ovarian cancer, and the LIN-28B/let-7a/IGF-II axis is associated with human disease. The purpose of this study was to investigate the associations between LIN-28B/let-7a/IGF-II axis molecular subtypes and epithelial ovarian cancer prognosis.
  
  
  METHODS
  Using quantitative reverse transcription PCR, we analyzed LIN-28B, let-7a and IGF-II mRNA in 211 primary epithelial ovarian cancer tissues, and also performed Classification and Regression Tree (CART) and survival analyses.
  
  
  RESULTS
  Four terminal subtypes were identified in the CART analysis in combination with survival analysis. Kaplan-Meier survival curves showed that subtypes LIN-28B(low)let-7a(low) and LIN-28B(low)let-7a(high)IGF-II(low) had significantly better survival than subtypes LIN-28B(high) or LIN-28B(low)let-7a(high)IGF-II(high) (p<0.0001 for overall, p=0.017 for progression-free survival, respectively). Multivariate Cox regression models showed that compared to subtype LIN-28B(high), subtypes LIN-28B(low)let-7a(low) and LIN-28B(low)let-7a(high)IGF-II(low) had significantly reduced mortality and reduced relapse risks. Moreover, subtype LIN-28B(low)let-7a(low) had better response to chemotherapy than subtype LIN-28B(high).
  
  
  CONCLUSIONS
  These results suggest that molecular subtypes of the LIN-28B/let-7a/IGF-II axis associate with heterogeneous progression and may have clinical implications in predicting epithelial ovarian cancer prognosis.
authors.affiliation: Department of Chronic Disease Epidemiology, School of Public Health, School of Medicine, Yale Cancer Center, Yale University, New Haven, CT 06520-8034, USA. Electronic address: lingeng.lu@yale.edu.
authors.forename: Lingeng
authors.initials: L
authors.lastname: Lu
authors.affiliation: Department of Surgical Science, A O Città della Salute e della Scienza di Torino, S.Anna Hospital, 10126 Turin, Italy.
authors.forename: Dionyssios
authors.initials: D
authors.lastname: Katsaros
authors.affiliation: Department of Surgical Science, A O Città della Salute e della Scienza di Torino, S.Anna Hospital, 10126 Turin, Italy.
authors.forename: Emilie Marion
authors.initials: EM
authors.lastname: Canuto
authors.affiliation: Department of Surgical Science, Division of Obstetrics and Gynecology, University of Torino School of Medicine, Mauriziano Hospital, 10128 Turin, Italy.
authors.forename: Nicoletta
authors.initials: N
authors.lastname: Biglia
authors.affiliation: Department of Chronic Disease Epidemiology, School of Public Health, School of Medicine, Yale Cancer Center, Yale University, New Haven, CT 06520-8034, USA.
authors.forename: Harvey A
authors.initials: HA
authors.lastname: Risch
authors.affiliation: Cancer Epidemiology Program, University of Hawaii Cancer Center, Honolulu, HI 96813, USA.
authors.forename: Herbert
authors.initials: H
authors.lastname: Yu
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000077216:Carcinoma, Ovarian Epithelial; D005260:Female; D006801:Humans; D007335:Insulin-Like Growth Factor II / Q000235:genetics / Q000502:physiology*; D035683:MicroRNAs / Q000235:genetics / Q000502:physiology*; D008875:Middle Aged; D009375:Neoplasms, Glandular and Epithelial / Q000235:genetics / Q000401:mortality* / Q000473:pathology; D010051:Ovarian Neoplasms / Q000235:genetics / Q000401:mortality* / Q000473:pathology; D011379:Prognosis; D016016:Proportional Hazards Models; D016601:RNA-Binding Proteins / Q000235:genetics / Q000502:physiology*
chemical_list: C516326:LIN28B protein, human; D035683:MicroRNAs; D016601:RNA-Binding Proteins; C487931:mirnlet7 microRNA, human; D007335:Insulin-Like Growth Factor II
keywords: Epithelial ovarian cancer; LIN-28B/let-7a/IGF-II axis; Molecular subtype; Prognosis