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

Abstract

Objectives 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-28Blowlet-7alow and LIN-28Blowlet-7ahigh IGF-IIlow had significantly better survival than subtypes LIN-28Bhigh or LIN-28Blow let-7ahigh 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-28Bhigh, subtypes LIN-28Blowlet-7alow and LIN-28Blowlet-7ahighIGF-IIlow had significantly reduced mortality and reduced relapse risks. Moreover, subtype LIN-28Blow let-7alow had better response to chemotherapy than subtype LIN-28Bhigh. 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.