成纤维细胞活化蛋白在非小细胞肺癌组织中的表达及其临床意义

Expression and clinical significance of fibroblast activation protein in non-small cell lung cancer

目的:检测人非小细胞肺癌(non-small cell lung cancer,NSCLC)组织中成纤维细胞活化蛋白(fibroblast activationprotein,FAP)mRNA的表达,探讨FAP mRNA与NSCLC临床特征及预后之间的关系。方法:2004年6月至2006年12月选取天津医科大学附属肿瘤医院组织库中247例NSCLC患者瘤组织标本和对应的48例癌旁组织标本,患者随访至2011年12月1日。采用实时荧光PCR检测NSCLC组织和正常肺组织中FAP mRNA。临床病理参数与FAP mRNA相对表达量的相关性分析采用Mann-Whitney U检验,以Kaplan-Meier法绘制生存曲线,用log-Rank检验比较患者的生存差异,采用Cox回归模型评估独立的预后因素。结果:FAP mRNA在NSCLC组织中过表达。NSCLC组织中FAP mRNA表达水平与NSCLC患者KPS评分成正相关(P<0.05),而与肿瘤原发部位、肿块大小、淋巴结转移、临床分期、组织学类型等其他病理特征无明显关系(P>0.05)。高表达FAP mRNA的NSCLC患者与低表达者相比,中位总生存时间(overall survival,OS)无明显差异(43 vs 39个月,P>0.05)。进一步以组织学类型分层分析显示,肺腺癌患者FAP mRNA表达量与临床分期成负相关(P=0.031),与KPS评分成正相关(P=0.041)。高表达FAP mRNA的肺腺癌患者与低表达者相比,中位OS时间显著延长(42 vs 26个月,P<0.05),多因素分析进一步证实FAP mRNA表达是影响肺腺癌患者预后的独立因素。结论:FAP在NSCLC组织中高表达,FAP mRNA高表达与肺腺癌的临床分期呈负相关,并与肺腺癌患者的预后密切相关。

Objective： To investigate the expression of fibroblast activation protein （FAP） mRNA in non-small cell lung cancer （NSCLC） tissue, and to evaluate its relationship with clinical characteristic and prognosis of NSCLC. Methods： Two hundred and forty-seven tumor specimens with NSCLC and forty-eight cases of corresponding adjacent tumor tissues selected from the Department of Biotherapy, Tumor Hospital Affiliated to Tianjing Medical University from June 2004 to December 2006. All cases were followed up until December 1,2011. The FAP mRNA was detected by real- time PCR in NSCLC and normal tissues. Mann-Whitney-Wilcoxon U-Test was used to evaluate the association between clinicopathological parameters and FAP mRNA expression. Survival curves were plotted using Kaplan-Meier method, and survival difference was compared by the Log-rank, with Cox regression model to evaluate the independent prognostic fac- tors. Results： FAP was over-expressed in NSCLC tissues. FAP mRNA expression level in NSCLC tissues were positively related to the Karnofsky Performance Score （KPS） （ P 〈 0.05 ） , but not to the primary tumor location, size of tumor,lymph node metastasis, clinical stage and pathologic type of tumor （P 〉 0.05 ）. The median overall survival （OS） be- tween patients with high FAP expression and low FAP expression showed no statistical significance （43 vs 39 months, P 〉 0.05）. Further histology hierarchical analysis showed that FAP mRNA expression in lung adenocarcinoma cancer patients was found to correlate inversely with clinical stages （P = 0. 031 ）, and correlate positively with KPS （P =0. 041 ）. Lung adenocarcinoma lung cancer patients with high FAP expression had longer OS than did patients with low FAP expression （42 vs 26 months, P 〈 0.05 ）. Multivariate analyses showed that FAP expression was an independent prognostic predictor of lung adenocarcinoma cancer patients. Conclusion： FAP is over-expressed in NSCLC tissues. FAP is found to correlate inversely with clinical stage of lung adenocarcinoma cancer, and the expression of FAP is closely related to prognosis of lung adenocarcinoma cancer patients.