LIN-28B/let-7a/IGF-II Axis Molecular Subtypes are Associated with Epithelial Ovarian Cancer Prognosis.
By: Lingeng Lu, Dionyssios Katsaros, Emilie Marion Canuto, Nicoletta Biglia, Harvey A Risch, Herbert Yu

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.
2015-8-18; doi: 10.1016/j.ygyno.2015.12.035
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 association 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.



Copyright © 2015. Published by Elsevier Inc.

PMID:26751131






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