Lu Lingeng, Katsaros Dionyssios, Risch Harvey A, Canuto Emilie Marion, Biglia Nicoletta, Yu Herbert
Department of Chronic Disease Epidemiology, Yale School of Public Health, School of Medicine, Yale Cancer Center, Yale University, New Haven, Connecticut.
Department of Surgical Science, A O Città della Salute e della Scienza di Torino, S. Anna Hospital, Turin, Italy.
Mol Carcinog. 2016 Apr;55(4):357-65. doi: 10.1002/mc.22285. Epub 2015 Jan 28.
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. © 2015 Wiley Periodicals, Inc.
在上皮性卵巢癌（EOC）中观察到自我更新基因HIWI和微小RNA（miRNA）let-7a的异常表达。HIWI表达与总生存期之间呈U形关联，这在几种人类癌症中可见，但在EOC中尚不清楚。HIWI直接和/或间接与let-7a相互作用，但其临床相关性仍有待探讨。在此，我们使用定量逆转录PCR分析了211例原发性EOC组织中的HIWI和let-7a表达，以研究HIWI及其与let-7a的相互作用在EOC预后中的意义。使用Kaplan-Meier生存曲线和Cox比例风险回归模型分析了HIWI及其与miRNA let-7a的相互作用与患者生存的相关性。Kaplan-Meier生存曲线显示，HIWI表达中等的患者总生存期比HIWI表达低或高的患者更差。在多变量Cox比例风险回归分析中，中等HIWI组的死亡风险增加了89%（HR = 1.89，95%CI：1.29 - 2.98）。在let-7a高表达的患者中，HIWI表达中等的患者与HIWI表达低的患者相比，死亡风险增加（HR = 2.62，95%CI：1.30 - 5.30），而在let-7a低表达的患者中，未观察到HIWI表达与总生存期之间的显著关联（HR = 1.63，95%CI：0.86 - 3.08）。此外，HIWI表达还影响化疗反应。结果表明，miRNA let-7a可以改变HIWI表达对EOC患者生存的影响，扩展了我们对HIWI与let-7a相互作用在EOC预后中的临床相关性的理解。© 2015 Wiley Periodicals, Inc.
