Sève Pascal, Isaac Sylvie, Trédan Olivier, Souquet Pierre-Jean, Pachéco Yves, Pérol Maurice, Lafanéchère Laurence, Penet Aurélie, Peiller Eva-Laure, Dumontet Charles
Service de Médecine Interne, Hôtel Dieu, Hospices Civils de Lyon, Lyon, France.
Clin Cancer Res. 2005 Aug 1;11(15):5481-6. doi: 10.1158/1078-0432.CCR-05-0285.
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).
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.
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 Delta2 alpha-tubulin expression was associated with a shorter overall survival (P = 0.018). Tubulin II 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 Delta2 alpha-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).
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.
确定局部晚期或转移性非小细胞肺癌（NSCLC）患者肿瘤中微管成分表达的患病率及其预后价值。
对93例未经治疗的III期和IV期NSCLC患者的肿瘤样本进行微管成分表达的免疫组化检测。所有患者均接受以长春瑞滨为基础的化疗。化疗反应、无进展生存期和总生存期与微管蛋白的表达相关。
缓解率为27.3%（77例有价值的患者中有21例部分缓解）。虽然微管成分的表达与缓解率无关，但高III类β-微管蛋白表达与对长春瑞滨的耐药性相关，定义为治疗期间疾病进展。肿瘤表达高水平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（分别为P = 0.002和0.001）。高Delta2α-微管蛋白表达与较短的总生存期相关（P = 0.018）。未发现微管蛋白II水平与患者预后相关。多因素分析考虑了性别、年龄、组织学、分期、体重减轻以及II类β-微管蛋白、III类β-微管蛋白和Delta2α-微管蛋白水平，证实III类β-微管蛋白表达与无进展生存期（P = 0.04）和总生存期（P = 0.012）独立相关。
这些发现表明，肿瘤细胞中高水平的III类β-微管蛋白表达与对长春瑞滨的耐药性以及接受以长春瑞滨为基础化疗的NSCLC患者的不良预后相关。
