多项肿瘤标记物的检测与晚期非小细胞肺癌化疗疗效及预后的关系

Relationship between the protein expression of ERCC1, BRCA, β-tubulin and K-ras and the efficacy and prognosis in advanced non-small cell lung cancer

目的检测以铂类为基础联合化疗的晚期非小细胞肺癌（NSCLC）患者中核苷酸切除修复交叉互补基因1（ERCC1）、乳腺癌敏感蛋白1型（BRCA1）、β微管蛋白（β-tubulin）和K-ras蛋白表达，探讨其与化疗疗效及预后的关系。方法采用免疫组化方法，检测136例以铂类为基础联合化疗的晚期NSCLC患者组织标本中ERCC1、BRCA1、β-tubulin和K—ras蛋白的表达，并分析表达状况与化疗疗效、预后之间的关系。结果（1）ERCC1阴性患者化疗后的客观有效率（ORR，38．6％）高于ERCC1阳性患者（26．4％，P〈0．017），ERCC1阴性患者的中位生存时间（MST，15个月）长于阳性患者（12个月，P〈0．05），两者无病生存时间（PFS）均为6个月（P〉0．05）。（2）BRCA1阴性患者的临床分期相对早于BRCA1阳性患者（P〈0．05），BRCA1阴性患者与阳性患者化疗后ORR分别为48．5％和37．1％，差异无统计学意义（P〉0．017）；BRCA1阴性患者的MST（16个月）长于阳性患者（9个月，P〈0．05），BRCA1阴性患者的PFS（7个月）长于阳性患者（6个月，P〈0．05）。（3）β-tubulin蛋白表达阴性患者与阳性患者化疗后ORR分别为42．9％和27．3％，差异无统计学意义（P〉0．017）；两者的MS与PFS比较，差异无统计学意义（P〉0．05）。（4）K—ras阴性患者化疗后ORR（36．0％）高于阳性患者（30．0％，P〈0．017），两者的MST与PFS比较，差异无统计学意义（P〉0．05）。（5）多因素分析显示，ERCC1蛋白表达是晚期NSCLC患者总生存的独立预后因素（P〈0．05）。结论ERCC1、BRCA1、β-tubulin和K-ras蛋白，对晚期NSCLC患者的化疗疗效及预后具有预测价值。

Objective To investigate the relationship between the expression of ERCC1, BRCA1, β-tubulin and K-ras and the clinical efficacy, prognosis in advanced non-small cell lung cancer treated by platinum-based chemotherapy. Methods Expression of ERCC1, BRCA1, β-tubulin and K-ras proteins were detected by immunohistochemistry in 136 patients. The relation between gene protein expression and efficacy, prognosis was analyzed. Results （ 1 ） The efficacy of chemotherapy （ORR） in the ERCC1 negative group was better than that in the ERCC1 positive group （ 38.6% vs. 26.4%, P 〈 0. 017 ）. The median survival time in the ERCC1 negative group was longer than that in the ERCC1 positive group（ 15 months vs. 12 months,P 〈0.05）. There was no significant difference in PFS. （2） The clinical stage in the BRCA1 negative group was earlier than that of positive group the BRCA1 negative group or BRCA1 positive group. There was no significant difference in ORR in either But both MST and PFS in the BRCA1 negative group was longer than that in the BRCA1 positive group （ 16 months vs. 9 months, P 〈 0.05 and 7 months vs. 7 months,P 〈0.05 ）, respcctovely. （3）There were no significant differences between the β-tubulin negative group and positive group in MST, PFS and ORR. （4）The ORR in the K-ras negative group was better than that in the K-ras positive group. There was no significant difference between the K-ras negative and positive groups in MST and PFS. （5）ERCC1 protein was an independent prognostic factor determined by multivariate analysis. Conclusions Muhi-biomarker detection may provide important predictive value for chemotherapy efficacy and prognosis in advanced NSCLC.