非小细胞肺癌血管内皮Nestin表达与临床病理指标及预后的相关性

Nestin expression in vascular endothelial cells in association with pathological indices and prognosis in non-small cell lung cancer

目的检测非小细胞肺癌组织血管内皮中Nestin的表达,分析其与非小细胞肺癌患者临床病理指标及预后的相关性。方法采用免疫组织化学方法检测非小细胞肺癌组织血管内皮中Nestin的表达。采用Mann-WhitneyU检验及Kruskal-Wallis法检验Nestin标志微血管密度(MVD)与临床病理指标的关系,采用Kaplan-Meier生存曲线计算无病生存期和生存时间,采用Log-rank检验进行差异检验,采用Cox分析评估各指标与患者生存之间的关系。结果患者组的Nestin-MVD计数水平显著高于对照组(P<0.01)。患者组中,不同病理类型、病理分期、T分期、N分期及血管侵犯情况患者的Nestin-MVD计数的差异均有统计学意义(P值均<0.05)。其中,腺癌患者的Nestin-MVD中位值(26.6)显著高于鳞癌患者(20.8,P=0.008);Ⅱ期和ⅢA期肺癌患者的Nestin-MVD中位值(23.0、25.1)显著高于ⅠB期患者(15.5,P值均=0.000);T1期和T3期患者的Nestin-MVD中位值(28.6、29.6)显著高于T2期患者(21.3,P值均=0.025);术中有淋巴结转移者(N分期为1～2)的Nestin-MVD中位值(23.7、24.8)显著高于未转移者(17.7,P值均=0.002);存在血管侵犯的肺癌患者的Nestin-MVD中位值(26.6)显著高于无血管侵犯者(21.3,P=0.021)。Nestin-MVD中位值>22.0的患者的中位无病生存期(DFS,16.5个月)、中位生存时间(OS,44.3个月)显著短于Nestin-MVD中位值≤22.0的患者(36.0和58.3个月,P值分别为0.002、0.004),其Nestin-MVD计数与DFS、OS呈负相关(Log-rank值分别为9.679和8.525,P值分别为0.002、0.004)。Cox单因素分析结果显示,病理分期(95%CI为1.222～2.175,P=0.001)、N分期(95%CI为1.175～2.062,P=0.002)、T分期(95%CI为1.050～2.705,P=0.031)、Nestin-MVD计数(95%CI为1.205～2.670,P=0.004)及有无血管侵犯(95%CI为1.007～2.282,P=0.046)均影响患者的OS;而年龄、性别、吸烟史、肿瘤大小、病理类型、分化程度及肿瘤组织有无坏死与患者的生存预后不相关(P值均>0.05)。Cox多因素分析结果显示,病理分期(95%CI为0.100～0.945,P=0.039)、N分期(95%CI为1.537～12.167,P=0.006)、T分期(95%CI为1.646～7.147,P=0.001)、Nestin-MVD计数(95%CI为1.139～2.795,P=0.012)为影响OS的独立危险因素。结论非小细胞肺癌血管内皮Nestin表达与肿瘤血管新生、转移及预后密切相关。

Objective To detect the expression of Nestin in vascular endothelial cells and to evaluate its correlation with pathological indices and prognosis in patients with non-small cell lung cancer （NSOLO）. Methods The expression of Nestin was detected by immunohistochemical staining. The relationship between microvessel desity （MVD） and pathological indexes was analyzed by Mann-Whitney U test and KruskaI-Wallis test. The disease-free survival and overall survival were calculated by Kaplan-Meier method. The difference in survival curves was evaluated with a Log-rank test. Univariate and multivariate analysis were carried out with Cox proportional-hazard model. Results Nestin-MVD level was significantly higher in cancers （P〈 0. 01 ）. Nestin-MVD was related to histologic classification, pathological stages, than in normal samples T stage, N stage and vascular invasion （all P〈0.05）. The median Nestin-MVD in adenocarcinoma was significantly higher than that in squamous cell carcinoma （26.2 vs. 20.8, P = 0. 008）. Compared with that in stage I （ 15.5）, the median Nestin- MVD was significantly increased in stage Ⅱ and stage Ⅲ（23.0 and 25. 1, both P = 0. 000）. The median Nestin- MVD in T1 and T3 stage was significantly higher than that in T2 stage （28.6 and 29.6 vs. 21.3, P = 0. 025）. The median Nestin-MVD in N1 stage and N2 stage was significantly higher than that in NO stage （23.7 and 24.8 vs. 17.7, P = 0. 002）. The median Nestin-MVD was significantly higher in NSCLC with vascular invasion than that without vascular invasion （26.6 vs. 21.3, P =0. 021）. The median Nestin-MVD value was slightly higher in NSCLC with necrosis than that without necrosis, while the differences had not statistical significance （P〉0.05）. Nestin-MVD was not related to age, sex, smoking status, tumor size or cell differentiation （all P〉0.05）. The disease-free survival was significantly shorter in the patients with Nestin-MVD〉22.0 than that in the patients with Nestin-MVD≤22.0 （16.5 months vs. 36.0 months, P = 0. 002）. So was the overall survival （44.3 months vs. 58.3 months, P = 0. 004）. Nestin-MVD level in patients with NSCLC was negatively related to DFS （Log rank= 9. 679, P= 0. 002） and OS （Log-rank = 8. 535, P = 0. 004）. Cox univariate analysis showed that TNM stage （95%CI 1.222-2. 175, P=0.001）, N stage （95%CI 1. 175-2.062, P=0.002）, T stage （95%C/ 1.050- 2.705, P = 0. 031）, Nestin-MVD level （95% CI 1. 205 - 2. 670, P = 0. 004） and vascular invasion （95% CI 1. 007-2. 282, P=0. 046） were related to overall survival of the NSCLC patients, while age, sex, smoking status, tumor size, histologic classification, cell differentiation and necrosis were not related to overall survival （all P〉0.05）. Cox multivariate analysis showed that TNM stage （95 % CI 0. 100 - 0. 945, P = 0. 039）, N stage （95 % CI 1. 537- 12. 167, P = 0. 006）, T stage （95 % OI 1. 646 - 7. 147, P = 0.001 ） and Nestin-MVD level （95 % CI 1. 139-2. 795, P = 0. 012） were the independent risk factors in these patients. Conclusion The expression of Nestin in vascular endothelial cells is closely related to tumor angiogenesis, metastasis and prognosis in NSCLC patients.