LIN-28B/let-7a/IGF-II axis molecular subtypes are associated with epithelial ovarian cancer prognosis

• Both LIN-28Bhigh, and LIN-28Blow/let-7ahigh/IGF-IIhigh signatures had high risks of relapse and overall mortality in EOC.
• EOC patients with the LIN-28Blow/let-7alow pattern had better response to chemotherapy.
• Four molecular subtypes were classified for EOC patients based on LIN-28B/let-7a/IGF-II axis.

ObjectivesAberrant 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.MethodsUsing 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.ResultsFour terminal subtypes were identified in the CART analysis in combination with survival analysis. Kaplan–Meier survival curves showed that subtypes LIN-28Blowlet-7alow and LIN-28Blowlet-7ahighIGF-IIlow had significantly better survival than subtypes LIN-28Bhigh or LIN-28Blowlet-7ahighIGF-IIhigh (p < 0.0001 for overall, p = 0.017 for progression-free survival, respectively). Multivariate Cox regression models showed that compared to subtype LIN-28Bhigh, subtypes LIN-28Blowlet-7alow and LIN-28Blowlet-7ahighIGF-IIlow had significantly reduced mortality and reduced relapse risks. Moreover, subtype LIN-28Blowlet-7alow had better response to chemotherapy than subtype LIN-28Bhigh.ConclusionsThese 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.