人类YB-1蛋白表达对肺腺癌术后患者预后及复发的影响

摘要

Background and purpose:The human Y-box binding protein, YB-1, is one of multifunctional proteins that regulates gene expression at both the transcriptional and translational levels. YB-1 has the potential to be used as a biomarker and predictor of multidrug resistance and prognosis in human cancers. This study was designed to detect YB-1 expression in lung adenocarcinoma by using immunohistochemical staining, and to evaluate the expression of YB-1 in patients with resected lung adenocarcinoma as well as its impact on their prognosis and recurrence. Methods:A total number of 174 lung adenocarcinoma patients who underwent surgical treatment were enrolled in this study. There were 99 men and 75 women with age of 65.0 years (range from 32 to 85). Immunohistochemical staining was done using by a streptavidin-biotin-peroxidase complex method (polyclonal anti-YB-1 antibody). The statistical significance was evaluated using the Pearson’s χ2 test. Survival curves were plotted according to the Kaplan–Meier method, and differences between the curves were analyzed by the log-rank test. The Cox proportional hazards model was applied to the univariate and multivariate survival analysis. Results:Positive expression of YB-1 was detected in the cytoplasm of tumor cells in 92 of 174 patients (52.9%) with lung adenocarcinoma. The positive expression of YB-1 was associated with poorly differentiated tumor (P=0.003), poor pathologic stage (P<0.001), lymph node metastasis (P=0.005) and tumor recurrence (P<0.001). The lung adenocarcinoma patients with positive YB-1 expression had a poorer prognosis than those with negative YB-1 expression, using both univariate and multivariate analyses (overall survival risk: P<0.001 and P=0.035, respectively). In addition, multivariate analysis of the clinicopathological characteristics with stageⅠlung adenocarcinoma indicated that the positive expression of YB-1 was a significant independent factor for predicting poor prognosis and early recurrence (P=0.048, HR=2.370 and P=0.057, HR=2.242, respectively). Conclusion:The expression of YB-1 plays an important role in predicting prognosis and recurrence in patients with resected lung adenocarcinoma, particularly patients with stageⅠdiseases.%　　背景与目的：人类Y盒结合蛋白,即YB-1蛋白是多功能蛋白之一,在转录与翻译两个水平调控基因表达,可作为预测人类恶性肿瘤多药耐药及判断预后的生物标记物.本文通过检测肺腺癌患者YB-1蛋白表达水平,评估YB-1蛋白在肺腺癌术后患者中的表达和对预后及复发的影响.方法：共收入174例接受肺腺癌切除术患者.其中99例男性,75例女性,平均年龄65.0岁(32~85岁).采用S-P法进行免疫组织化学染色(抗YB-1多克隆抗体).利用χ2检验进行统计学分析,Kaplan-Meier法绘制生存曲线,log-rank检验比较曲线间差异,Cox比例危险模型进行单因素及多因素分析.结果：在174例肺腺癌患者中,92例(52.9%)YB-1蛋白细胞质表达阳性.YB-1蛋白表达阳性组肿瘤细胞的分化较差(P=0.003),病理分期较晚(P<0.001),淋巴结转移较显著(P=0.005),肿瘤复发较早(P<0.001).单因素及多因素分析表明,YB-1蛋白表达阳性组预后明显较YB-1蛋白表达阴性组差(总体生存风险分别为P<0.001和P=0.035).此外,在对其中102例Ⅰ期肺腺癌患者各临床病理因子的多因素分析提示,YB-1蛋白表达阳性是预测患者预后不良及肿瘤早期复发的独立危险因子(分别为P=0.048, HR=2.370和P=0.057,HR=2.242).结论：YB-1蛋白表达水平可作为预测肺腺癌术后患者(尤其是Ⅰ期肺腺癌患者)预后及复发的指标.