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Mol Carcinog. 2016 Apr;55(4):357-65. doi: 10.1002/mc.22285. Epub 2015 Jan 28.

MicroRNA let-7a modifies the effect of self-renewal gene HIWI on patient survival of epithelial ovarian cancer.

Author information

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

Abstract

Aberrant expressions of self-renewal gene HIWI and microRNA (miRNA) let-7a are observed in epithelial ovarian cancer (EOC). A U-shape association between HIWI expression and overall survival is seen in several human cancers but unknown in EOC. HIWI directly and/or indirectly interacts with let-7a, but the clinical relevance of this interaction is yet to be addressed. Here, we analyzed HIWI and let-7a expressions in 211 primary EOC tissues using quantitative reverse-transcription PCR to investigate HIWI and its interaction with let-7a in the prognostic significance of EOC. Associations of HIWI and its interaction with miRNA let-7a with patient survival were analyzed using the Kaplan-Meier survival curves and Cox proportional hazard regression models. Kaplan-Meier survival curves showed that patients with medium HIWI had poorer overall survival than those with low or high HIWI. An 89% increased death risk (HR = 1.89, 95% CI: 1.29-2.98) was observed in the medium HIWI group in multivariate Cox proportional hazard regression analyses. Among patients with high let-7a expression, those with medium HIWI had an increased risk of death compared to those with low HIWI (HR = 2.62, 95% CI: 1.30-5.30), whereas among those with low let-7a, no significant association between HIWI expression and overall survival was observed (HR = 1.63, 95% CI: 0.86-3.08). Moreover, HIWI expression also affected chemotherapy response. The results suggested that miRNA let-7a could modify the effect of HIWI expression on patient survival of EOC, expanding our understanding of the clinical relevance of HIWI and let-7a interaction in EOC prognosis.

KEYWORDS:

epithelial ovarian cancer; let-7a; piwi-like RNA-mediated gene silencing 1 (PIWIL1 or HIWI); prognosis

PMID:
25630839
DOI:
10.1002/mc.22285
[Indexed for MEDLINE]
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