ERCC1基因蛋白表达与非小细胞肺癌顺铂辅助化疗的关系

山东大学学报(医学版)

ERCC1基因蛋白表达与非小细胞肺癌顺铂辅助化疗的关系

吴铭生¹,王苹²,林俊豪³,王谦⁴,吴树明³

山东大学齐鲁医院 1. 胸外科； 2. 放射科； 3. 心外科； 4. 检验科，济南 250012

收稿日期:2008-02-05 修回日期:1900-01-01 出版日期:2008-06-16 发布日期:2008-06-16
通讯作者: 吴树明

ERCC1 expression and cisplatin based adjuvant chemotherapy in non-small cell lung cancer

WU Ming-sheng¹, WANG Ping², LIN Jun-hao¹, WANG Qian³, WU Shu-ming¹

1. Department of Thoracic Surgery; 2. Department of Xray; 3. Department of Cardiac Surgery;4. Department of Laboratory, Qilu Hospital of Shandong University

Received:2008-02-05 Revised:1900-01-01 Online:2008-06-16 Published:2008-06-16
Contact: WU Shu-ming

摘要/Abstract

摘要： 目的探讨核苷酸切除修复交叉互补组（ERCC1）基因蛋白表达与非小细胞肺癌(NSCLC)顺铂辅助化疗之间的关系及铂类药物在NSCLC辅助化疗中发生耐药的机制。方法应用免疫组化方法对112例NSCLC患者手术切除标本石蜡包埋组织切片ERCC1基因蛋白表达进行了测定，并结合患者年龄、组织病理学类型、TNM分期、化疗及生存情况尤其是ERCC1基因蛋白表达与NSCLC患者铂类药物辅助化疗之间的生存情况进行分析。结果ERCC1基因蛋白表达阳性NSCLC患者，应用顺铂辅助化疗，其生存时间明显低于未用顺铂辅助化疗者，差异有统计学意义（P＜0.01）；ERCC1基因蛋白表达阴性NSCLC患者，应用顺铂辅助化疗其生存时间与未用顺铂辅助化疗者的生存时间无统计学意义（P＞0.05），但前者有优于后者的趋势。在排除了ERCC1基因蛋白表达的影响后，NSCLC患者不同年龄、TNM分期、组织病理学类型与生存时间关系的分析显示，NSCLC患者年龄与生存时间之间无明显相关性（χ²=1.008, P=0.297）；TNM分期与生存时间之间呈明显相关性（χ²=51.326, P=0.000）；组织病理学类型与生存时间之间有相关性（χ²=6.339, P=0.012），腺癌的生存时间要高于鳞癌。分析结果显示，ERCC1基因蛋白表达阳性患者无论在年龄、TNM分期、病理类型等方面，其生存时间均都明显长于阴性者。结论① ERCC1基因蛋白表达阴性患者应用顺铂辅助化疗可能获得生存受益；② ERCC1基因蛋白表达阳性提示对于铂类药物耐药而言，ERCC1基因蛋白表达可能成为NSCLC患者是否应用顺铂辅助化疗的指标之一；③ ERCC1基因蛋白表达可能成为NSCLC患者的一个重要的预后指标。

关键词: 化学疗法, 辅助, 核苷酸切除修复交叉互补组基因蛋白, 顺铂, 非小细胞肺, 癌

Abstract: To explore the relationship between excision repair crosscomplementation group 1 (ERCC1) protein expression and clinical outcome of cis-platinum based adjuvant chemotherapy in non small cell lung cancer (NSCLC), in order to understand the possible mechanism of cisplatinum resistance in NSCLC and provide predictive bio-markers to tailor adjuvant chemotherapy regimens and improve survival and response in NSCLC patients. Methods We examined the ERCC1 expression in 112 NSCLC patients by immunohistochemical staining of paraffin embedded tumor tissues, analyzed the relationship between the ERCC1 expression and NSCLC patients′ age, pathology category, TNM stage, chemotherapy and survival, especially focusing on the relationship between the ERCC1 expression and adjuvant cis-platinum based chemotherapy and survival of NSCLC patients. ResultsIn NSCLC patients with positive ERCC1 protein expression, the survival of those who received adjuvant cis-platinum chemotherapy was significantly shorter than that of those did not receive adjuvant cis-platinum chemotherapy (P＜0.01); in NSCLC patients with negative ERCC1 expression, there were no significant differences between the survival of those with and without adjuvant cisplatin chemotherapy (P＞0.05), but there were trends that the former was longer than the latter. After excluding ERCC1 expression, survival was not related to patient age (χ²=1.008, P=0.297), but related to TNM stages; the earlier the TNM stages, the longer the survival (χ²=51.326, P=0.000); also it was related to pathological categories: the survival of adenocarcinoma was longer than that of squamous cell carcinoma (χ²=6.339, P=0.012). In all subgroups (patient age, TNM stage, pathology category), the survival of ERCC1 positive patients was longer than that of ERCC1 negative patients. Conclusion1. Cis-platinum chemotherapy may benefit the NSCLC patient with negative expression of ERCC1. 2. Positive ERCC1 expression indicates cisplatinum resistance, so ERCC1 may be used as a predictive bio-marker to tailor adjuvant chemotherapy. 3. ERCC1 protein expression might be an important index for prognosis.

Key words: Carcinoma, nonsmall cell lung, Excision repair crosscomplementation group 1, Cisplatin, Chemotherapy, adjuvant

中图分类号:

R319

吴铭生,王苹,林俊豪,王谦,吴树明 . ERCC1基因蛋白表达与非小细胞肺癌顺铂辅助化疗的关系[J]. 山东大学学报(医学版), 2008, 46(6): 556-560.

WU Ming-sheng,WANG Ping,LIN Jun-hao,WANG Qian,WU Shu-ming. ERCC1 expression and cisplatin based adjuvant chemotherapy in non-small cell lung cancer[J]. JOURNAL OF SHANDONG UNIVERSITY (HEALTH SCIENCES), 2008, 46(6): 556-560.

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