Assessment of IAP (inhibitor of apoptosis) proteins as predictors of response to chemotherapy in advanced non-small-cell lung cancer patients
Assessment of IAP (inhibitor of apoptosis) proteins as predictors of response to chemotherapy in advanced non-small-cell lung cancer patients
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DOI：
10.1023/a:1011167113067
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发表时间：
2001-06-01
影响因子：
50.5
通讯作者：
Giaccone, G
中科院分区：
文献类型：
--
作者：
Ferreira, CG;van der Valk, P;Giaccone, G
背景资料：细胞凋亡抑制因子家族蛋白（IAP）的表达在体外已显示通过半胱天冬酶抑制降低化疗敏感性。然而，IAP作为癌症患者化疗反应的预测因子的作用仍有待确定。患者和方法：使用免疫组织化学，我们评估了55例接受化疗的晚期非小细胞肺癌（NSCLC）患者肿瘤上IAP蛋白c-IAP 1、c-IAP 2和XIAP的表达，并将其与观察到的化疗反应相关联，结果：IAP蛋白的染色模式存在差异。c-IAP 2和XIAP的表达仅在细胞质中，而c-IAP 1也显示细胞核染色。c-IAP 1、c-IAP 2和XIAP的肿瘤细胞中位表达分别为70%、45%和25%，并且在c-IAP 1和c-IAP 2（P = 0.004）以及c-IAP 1和XIAP表达（P = 0.013）之间观察到相关性。然而，这些蛋白质的表达与性别、年龄、肿瘤大小、分期、组织学和分化程度之间没有相关性。有趣的是，c-IAP 1、c-IAP 2和XIAP的表达并不能预测对化疗的反应。此外，IAP的表达没有影响的时间进展或这组patients.Conclusions的总生存期：我们的研究结果表明：1）有差异的表达水平和亚细胞分布的c-IAP 1，c-IAP 2，和XIAP来源于NSCLC患者的肿瘤。2)c-IAP 1、c-IAP 2和XIAP的表达不能预测晚期NSCLC患者对化疗的反应。3)癌症患者中IAP表达与化疗敏感性之间的关系可能比体外数据预期的更复杂。
Background: Expression of inhibitor of apoptosis family proteins (IAPs) has been shown in vitro to decrease chemosensitivity through caspase inhibition. However, the role of IAPs as predictors of response to chemotherapy in cancer patients remains to be determined.Patients and methods: Using immunohistochemistry, we assessed the expression of the IAP proteins c-IAP1, c-IAP2, and XIAP on tumors from 55 patients with advanced non-small-cell lung cancer (NSCLC) treated with chemotherapy, and correlated that with the observed response to chemotherapy, time to progression and overall survival.Results: Differences were observed in the pattern of staining among the IAP proteins. The expression of c-IAP2 and XIAP was exclusively cytoplasmic, whereas c-IAP1 also displayed nuclear staining. The median expression of tumor cells for c-IAP1, c-IAP2, and XIAP was 70%, 45%, and 25%, respectively, and a correlation was observed between c-IAP1 and c-IAP2 (P = 0.004), and c-IAP1 and XIAP expression (P = 0.013). However, no association was seen between the expression of these proteins and sex, age, tumor size, stage, histology and grade of differentiation. Interestingly, expression of c-IAP1, c-IAP2, and XIAP did not predict response to chemotherapy. In addition, the expression of IAPs had no impact on the time to progression or overall survival of this group of patients.Conclusions: Our results indicate that: 1) there are differences in the level of expression and in the subcellular distribution of c-IAP1, c-IAP2, and XIAP in tumors derived from NSCLC patients. 2) The expression of c-IAP1, c-IAP2 and XIAP does not predict the response to chemotherapy in patients with advanced NSCLC. 3) The relation between expression of IAPs and chemosensitivity in cancer patients may be more complex than anticipated by in vitro data.