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Gynecol Oncol. 2016 Apr;141(1):121-7. doi: 10.1016/j.ygyno.2015.12.035. Epub 2016 Jan 2.

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

Author information

1
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.
2
Department of Surgical Science, A O Città della Salute e della Scienza di Torino, S.Anna Hospital, 10126 Turin, Italy.
3
Department of Surgical Science, Division of Obstetrics and Gynecology, University of Torino School of Medicine, Mauriziano Hospital, 10128 Turin, Italy.
4
Department of Chronic Disease Epidemiology, School of Public Health, School of Medicine, Yale Cancer Center, Yale University, New Haven, CT 06520-8034, USA.
5
Cancer Epidemiology Program, University of Hawaii Cancer Center, Honolulu, HI 96813, USA.

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-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.

KEYWORDS:

Epithelial ovarian cancer; LIN-28B/let-7a/IGF-II axis; Molecular subtype; Prognosis

PMID:
26751131
DOI:
10.1016/j.ygyno.2015.12.035
[Indexed for MEDLINE]
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