Ⅱb/Ⅲa期非小细胞肺癌患者肿瘤RRM1蛋白的表达意义

Expression and clinical significance of RRM1 protein in non-small cell lung cancer at stage of Ⅱb/Ⅲa

摘要:

目的：研究核苷酸还原酶M1亚基（Ribonucleotide reductase subunit M1，RRM1）蛋白在Ⅱb/Ⅲa期非小细胞肺癌（Non-small cell lung cancer，NSCLC）术后患者中的表达及RRM1蛋白表达对辅助化疗无疾病生存期（Disease free survival，DFS）的影响。方法：采用链霉菌抗生物素蛋白-过氧化酶染色（Streptavidin-perosidase，SP）法回顾性检测100例Ⅱb/Ⅲa期NSCLC根治术后患者肿瘤组织RRM1蛋白表达，分析其表达状况与患者临床特征之间的关系，并使用SPSS 13.0进行统计，研究分析其对患者预后的影响。结果：（1）RRM1蛋白在不同的性别、吸烟状况、分化程度、病理分期及不同治疗组中表达无明显差异（P >0.05），RRM1蛋白表达在鳞癌患者中高于非鳞癌患者，但无统计学差异（44.1%/30.3%，P=0.172）；（2）在入组患者中，RRM1蛋白低表达较RRM1蛋白高表达患者DFS时间明显延长（中位时间，14月/8月，P=0.019 4）；（3）亚组分析中，吉西他滨/顺铂方案辅助化疗组，鳞癌患者较非鳞癌患者DFS时间明显延长（中位时间，14月/11月，P=0.011 9）；接受吉西他滨/顺铂方案辅助化疗组的患者中，RRM1蛋白低表达患者DFS较高表达患者明显延长（中位时间，13月/6月，P=0.021 7），但在单纯接受手术组的患者中不同RRM1蛋白表达的患者中DFS无明显差异（中位时间，15.5月/13月，P >0.05）；（4）COX多因素分析显示只有RRMl蛋白表达和病理类型是Ⅱb/Ⅲa期NSCLC的独立影响因素（P均<0．005）。结论：在Ⅱb/Ⅲa 期NSCLC患者中，RRM1蛋白可能是患者吉西他滨/顺铂辅助化疗方案疗效的预测因子。

Abstract:

Objective：To investigate the postoperative expression of ribonucleotide reductase subunit M1（RRM1） protein in non-small cell lung cancer（NSCLC） at stage of Ⅱ b/Ⅲ and to discuss the effect of RRM1 protein expression on disease free survival（DFS） of patients underwent adjuvant chemotherapy. Methods：Totally 100 patients with NSCLC at stage of Ⅱb/Ⅲa who underwent radical surgery were included in this study. The expression of RRM1 protein in tumor specimens was assayed by streptavidin-perosidase（SP）immunohistochemistry retrospectively. Correlations between the expression of RRM1 protein and the clinical features or DFS time af－ter operation were analyzed. SPSS 13.0 was used to analyze the effect of RRM1 protein expression on the patients’ prognosis. Results：（1）No difference in the expression of RRM1 protein was found among patients with different genders，ages，smoking habits，patho－logical differentiation and stages（P＞0.05）. RRM1 protein expression was increased in squamous carcinoma than in non-squamous car－cinoma although there was no significant difference（44.1% vs. 30.3%，P=0.172）；（2）Patients with lower RRM1 protein expression ex－perienced longer DFS time compared with those with higher RRM1 protein expression（median DFS，14 months vs. 8 months，P=0.019 4）；（3）In patients with adjuvant chemotherapy of Gemcitabine/Cisplatin，squamous carcinoma led to longer DFS time than non squamous carcinoma（median DFS，14 months vs. 11 months，P=0.011 9）；lower RRM1 protein expression led to longer DFS time than higher RRM1 protein expression（median DFS，13 months vs. 6 months，P=0.021 7）. No difference in the length of DFS time was found in the patients with only surgery（median DFS，15.5 months vs. 13 months，P >0.05）. （4）COX multivariate regression analysis showed that the expression of RRM1 protein and pathological type were the independent prognostic factors of DFS in NSCLC at stage of Ⅱb/Ⅲa. Conclusion：RRM1 protein is a valuable predictive factor for Gemcitabine/Cisplatin adjuvant chemotherapy in NSCLC at stage of Ⅱb/Ⅲa.