铂类和紫杉类为基础的新辅助化疗和手术切除治疗的非小细胞肺癌患者中 ERCC1、BRCA1、XRCC1 和βIII-微管蛋白表达的预后意义。
The prognostic significance of ERCC1, BRCA1, XRCC1, and betaIII-tubulin expression in patients with non-small cell lung cancer treated by platinum- and taxane-based neoadjuvant chemotherapy and surgical resection.
机构信息
Department of Thoracic and Cardiovascular Surgery, Seoul National University Hospital, Seoul National University College of Medicine, 28 Yongon-dong, Chongro-gu, Seoul 110-744, South Korea.
出版信息
Lung Cancer. 2010 Jun;68(3):478-83. doi: 10.1016/j.lungcan.2009.07.004. Epub 2009 Aug 15.
OBJECTIVES
The DNA repair pathway and isotype composition of beta-tubulin are known to be associated with resistance to platinum- and taxane-based chemotherapy, respectively. The aim of this study was to identify the clinical significance of excision repair cross-complementation 1 (ERCC1), breast cancer susceptibility gene 1 (BRCA1), X-ray repair cross-complementation 1 (XRCC1) and betaIII-tubulin on the chemotherapy response and overall survival in patients with non-small cell lung cancer (NSCLC) who received neoadjuvant chemotherapy.
METHODS
Protein expression profiles were evaluated by immunohistochemistry on surgical specimens of 82 NSCLC patients who underwent platinum- and taxane-based neoadjuvant chemotherapy. The expression levels of proteins were measured semi-quantitatively and the correlation with tumor responses, pathologic cell death rate and survival were evaluated.
RESULTS
There were 73 (89.0%) clinical stage III patients. Lobectomy, bilobectomy, and pneumonectomy were performed in 54 (65.0%), 11 (13.4%), and 17 (20.7%) patients, respectively. There was no correlation between clinical response and protein expression. The expression levels of ERCC1, BRCA1, and XRCC1 increased proportionally to the cell death rate (p<0.05); however, betaIII-tubulin expression did not correlate with cell viability. Multivariate analysis demonstrated that early pathologic stage, adjuvant chemotherapy, high ERCC1 and low betaIII-tubulin expression were good prognostic factors for overall survival (p<0.05).
CONCLUSIONS
The inverse correlation between DNA repair proteins and cell viability suggests that these protein expression levels can be markers for chemotherapy responsiveness. However, only ERCC1 and betaIII-tubulin were prognostic factors after platinum- and taxane-based neoadjuvant chemotherapy following surgical resection.
目的
β-微管蛋白的 DNA 修复途径和同种型组成分别与铂类和紫杉烷类化疗耐药相关。本研究旨在确定切除修复交叉互补基因 1（ERCC1）、乳腺癌易感基因 1（BRCA1）、X 射线修复交叉互补基因 1（XRCC1）和βIII-微管蛋白在接受铂类和紫杉烷类新辅助化疗的非小细胞肺癌（NSCLC）患者化疗反应和总生存中的临床意义。
方法
对 82 例接受铂类和紫杉烷类新辅助化疗的 NSCLC 患者的手术标本进行免疫组织化学检测，评估蛋白质表达谱。采用半定量方法测量蛋白质的表达水平，并评估其与肿瘤反应、病理细胞死亡率和生存的相关性。
结果
73 例（89.0%）为临床 III 期患者。54 例（65.0%）患者行肺叶切除术、双肺叶切除术和全肺切除术，11 例（13.4%）和 17 例（20.7%）患者行肺段切除术和肺楔形切除术。临床反应与蛋白表达无相关性。ERCC1、BRCA1 和 XRCC1 的表达水平与细胞死亡率成正比（p<0.05）；然而，βIII-微管蛋白的表达与细胞活力无关。多变量分析表明，早期病理分期、辅助化疗、高 ERCC1 和低βIII-微管蛋白表达是总生存的良好预后因素（p<0.05）。
结论
DNA 修复蛋白与细胞活力呈负相关，提示这些蛋白表达水平可作为化疗反应性的标志物。然而，只有 ERCC1 和βIII-微管蛋白是铂类和紫杉烷类新辅助化疗后手术切除的预后因素。
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