Wee1 is a novel independent prognostic marker of poor survival in post-chemotherapy ovarian carcinoma effusions
Wee1 is a novel independent prognostic marker of poor survival in post-chemotherapy ovarian carcinoma effusions
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DOI：
10.1016/j.ygyno.2014.07.102
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发表时间：
2014-10-01
影响因子：
4.7
通讯作者：
Florenes, Vivi Ann
中科院分区：
文献类型：
--
作者：
Slipicevic, Ana;Holth, Arild;Florenes, Vivi Ann
目标。Wee1样激酶（Wee1）是一种酪氨酸激酶，在G2期向m期过渡时负调控有丝分裂的进入，并在s期抑制非预定的DNA复制。本研究探讨了Wee1在晚期（FIGO III-IV）卵巢浆液性癌中的临床作用。采用免疫组化方法分析287例积液中Wee1蛋白的表达。分析表达与临床病理参数（包括生存）的关系。另外用Western blotting对45例积液进行了研究。通过siRNA敲低SKOV3和OVCAR8细胞，进一步沉默Wee1，并观察其增殖情况。免疫组化和免疫印迹法分别在265/287（92%）和45/45（100%）的肿瘤细胞积液中观察到Wee1的核表达。与诊断时获得的化疗前积液相比，化疗后疾病复发中免疫组织化学检测的Wee1表达显著升高（p = 0.002）。SKOV3和OVCAR8细胞中Wee1的沉默降低了细胞的增殖。在整个队列的单因素生存分析中，观察到Wee1高表达（bbbb25 %的细胞）与总生存差之间的趋势（p = 0.083）。109例化疗后积液患者的生存分析显示，Wee1表达与总生存差有显著相关性（p = 0.004），这一发现在Cox多因素分析中仍具有独立的预后作用（p = 0.003）。Wee1在卵巢浆液性癌积液中频繁表达，化疗后表达明显增高。本研究首次报道Wee1是浆液性卵巢癌的独立预后标志物。(C) 2014爱思唯尔公司版权所有。
Objective. Wee1-like kinase (Wee1) is a tyrosine kinase which negatively regulates entry into mitosis at the G2 to M-phase transition and has a role in inhibition of unscheduled DNA replication in S-phase. The present study investigated the clinical role of Wee1 in advanced-stage (FIGO III-IV) ovarian serous carcinoma.Methods. Wee1 protein expression was analyzed in 287 effusions using immunohistochemistry. Expression was analyzed for association with clinicopathologic parameters, including survival. Forty-five effusions were additionally studied using Western blotting. Wee1 was further silenced in SKOV3 and OVCAR8 cells by siRNA knockdown and proliferation was assessed.Results. Nuclear expression of Wee1 in tumor cells was observed in 265/287 (92%) and 45/45 (100%) effusions by immunohistochemistry and Western blotting, respectively. Wee1 expression by immunohistochemistry was significantly higher in post-chemotherapy disease recurrence compared to pre-chemotherapy effusions obtained at diagnosis (p = 0.002). Wee1 silencing in SKOV3 and OVCAR8 cells reduced proliferation. In univariate survival analysis of the entire cohort, a trend was observed between high (>25% of cells) Wee1 expression and poor overall survival (p = 0.083). Survival analysis for 109 patients with post-chemotherapy effusions showed significant association between Wee1 expression and poor overall survival (p = 0.004), a finding which retained its independent prognostic role in Cox multivariate analysis (p = 0.003).Conclusions. Wee1 is frequently expressed in ovarian serous carcinoma effusions, and its expression is significantly higher following exposure to chemotherapy. The present study is the first to report that Wee1 is an independent prognostic marker in serous ovarian carcinoma. (C) 2014 Elsevier Inc. All rights reserved.