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首页> 外文期刊>British Journal of Cancer >X-chromosome-linked inhibitor of apoptosis as a key factor for chemoresistance in clear cell carcinoma of the ovary
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X-chromosome-linked inhibitor of apoptosis as a key factor for chemoresistance in clear cell carcinoma of the ovary

机译：X染色体连锁的凋亡抑制剂是卵巢透明细胞癌化学耐药的关键因素

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Background: X-chromosome-linked inhibitor of apoptosis (XIAP) is one of the anti-apoptotic proteins leading to chemoresistance in several cancers. The aim of this study is to evaluate the impact of XIAP expression upon ovarian clear cell carcinoma (CCC) that has a platinum-resistant phenotype.Methods: Tissue microarrays made from 90 CCC patients were analysed for immunohistochemical expression levels of XIAP, c-Met, p-Akt and Bcl-XL. In addition, CCC cell lines were evaluated whether XIAP silencing could modulate sensitivity to platinum agent in vitro. Results: High XIAP expression was observed in 30 (33%) of 90 CCC cases, and was associated with c-Met (<0.01) and Bcl-XL (<0.01) expression. Cases with high XIAP expression had lower response rate to primary platinum-based chemotherapy (10% vs 65%, P =0.02). In stages II–IV tumours, high XIAP expression was related with worse progression-free survival (PFS, P =0.02). Furthermore, high XIAP expression was identified as an independent worse prognostic factor for PFS and overall survival. Finally, downregulation of XIAP using XIAP-specific small interfering RNA increased sensitivity to cisplatin in human cancer cells derived from CCC.Conclusions: X-chromosome-linked inhibitor of apoptosis expression was correlated with chemoresistance of primary chemotherapy, and identified as a prognostic marker for CCC. X-chromosome-linked inhibitor of apoptosis could be a candidate for new therapeutic target in CCC.
机译：背景：X染色体连锁的细胞凋亡抑制剂（XIAP）是导致几种癌症化学耐药性的抗凋亡蛋白之一。这项研究的目的是评估XIAP表达对具有铂抗性表型的卵巢透明细胞癌（CCC）的影响。方法：分析了90例CCC患者的组织芯片，​​分析了XIAP，c-Met的免疫组织化学表达水平。 ，p-Akt和Bcl-XL。此外，评估了CCC细胞系XIAP沉默能否在体外调节对铂试剂的敏感性。结果：90例CCC患者中有30例（33％）观察到高XIAP表达，并与c-Met（<0.01）和Bcl-XL（<0.01）表达相关。 XIAP表达高的病例对基于铂的原发化疗的反应率较低（10％比65％，P = 0.02）。在II–IV期肿瘤中，高XIAP表达与较差的无进展生存期相关（PFS，P = 0.02）。此外，XIAP高表达被确定为PFS和总体生存的独立不良预后因素。最后，使用XIAP特异性小干扰RNA来下调XIAP可以增加源自CCC的人类癌细胞对顺铂的敏感性。 CCC。 X染色体连锁的细胞凋亡抑制剂可能是CCC新治疗靶点的候选药物。

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