Expression of class III β-tubulin is predictive of patient outcome in patients with non-small cell lung cancer receiving vinorelbine-based chemotherapy
Expression of class III β-tubulin is predictive of patient outcome in patients with non-small cell lung cancer receiving vinorelbine-based chemotherapy
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DOI：
10.1158/1078-0432.ccr-05-0285
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发表时间：
2005-08-01
影响因子：
11.5
通讯作者：
Dumontet, C
中科院分区：
文献类型：
--
作者：
Sève, P;Isaac, S;Dumontet, C
目的：探讨微管成分在局部晚期或转移性非小细胞肺癌(NSCLC)患者肿瘤中的表达及其预后价值。实验设计：采用免疫组织化学方法检测93例初治III、IV期非小细胞肺癌患者肿瘤组织中微管成分的表达。所有患者均接受了以长春瑞滨为基础的化疗。微管蛋白的表达与化疗疗效、无进展生存期和总生存期相关。结果：77例患者中有21例部分缓解，有效率为27.3%。虽然微管成分的表达与应答率无关，但III型β-微管蛋白的高表达与对长春瑞滨的耐药性有关，长春瑞滨被定义为治疗下的疾病进展。高表达III类β-微管蛋白亚型的患者无进展生存期和总生存期较短(P分别为0.002和0.001)。Delta2α微管蛋白的高表达与总生存期缩短有关(P=0.018)。未发现微管蛋白11水平与患者预后相关。考虑到性别、年龄、组织学、分期、体重减轻、II类β微管蛋白、III类β微管蛋白和Delta 2β微管蛋白水平的多因素分析证实，III类β微管蛋白的表达与无进展生存期(P=0.04)和总生存期(P=0.012)独立相关。结论：在接受长春瑞滨化疗的非小细胞肺癌患者中，III类β微管蛋白的高表达与长春瑞滨耐药和预后不良有关。
Purpose: To determine the prevalence and the prognostic value of microtubule component expression in tumors of patients with locally advanced or metastatic non-small cell lung cancer (NSCLC).Experimental Design: Expression of microtubular components was immunohistochemically examined in 93 tumor samples from untreated patients with stage III and IV NSCLC. All patients received vinorelbine-based chemotherapy. Response to chemotherapy, progression-free survival, and overall survival were correlated with the expression of microtubule proteins.Results: The response rate was 27.3% (21 partial responses among 77 valuable patients). Although expression of microtubule components was not associated with the response rate, high class III beta-tubulin expression was correlated with resistance to vinorelbine, defined as disease progression under treatment. Patients whose tumors expressed high levels of class III beta-tubulin isotype had shorter progression-free survival and overall survival (P = 0.002 and 0.001, respectively). High Delta 2 alpha-tubulin expression was associated with a shorter overall survival (P = 0.018). Tubulin 11 levels were not found to be correlated with patient outcome. A multivariate analysis, taking into account sex, age, histology, stage, weight loss, and class II beta-tubulin, class III beta-tubulin, and Delta 2 beta-tubulin levels, confirmed that class III beta-tubulin expression was independently correlated with progression-free survival (P = 0.04) and overall survival (P = 0.012).Conclusions: These findings suggest that a high level of expression of class III beta-tubulin in tumor cells is associated with resistance to vinorelbine and a poor prognosis in patients with NSCLC receiving vinorelbine-based chemotherapy.