纤维连接蛋白1在膀胱癌组织的表达及临床意义  

Cfinical significance of expression of fibronecfin 1 in bladder cancer

作　　者：陈子坚[1] 陈明坤[1] 黄仲曦[2] 李欣[2] 秦自科[3] 温伟杰[3] 杨建昆[1] 卞军[1] 周俊豪[1] 杨诚[1] 夏慧[1] 刘存东[1] 

机构地区：[1]南方医科大学第三附属医院泌尿外科,广州510630 [2]南方医科大学肿瘤研究所,广州510515 [3]中山大学肿瘤防治中心泌尿外科,广州510060

出　　处：《中华实验外科杂志》2016年第6期1444-1447,共4页Chinese Journal of Experimental Surgery

基　　金：基金项目：广东省医学科研基金（A2014430）;广东省自然科学基金-博士启动项目（2104A030310017）;南方医科大学优秀青年科研人员启动项目（PY2013N064）

摘　　要：目的检测纤维连接蛋白1（FN1）在膀胱癌组织中的表达水平及对膀胱癌预后的影响。方法从Gene expression omnibus（GEO）数据库下载4套膀胱癌基因芯片数据集，共有132例肌层浸润性和55例表浅性膀胱癌组织的基因芯片数据纳入实验分析。生物信息学分析FN1在膀胱癌中的表达，并用实时荧光定量聚合酶链反应（FQ-PCR）验证FN1在59例膀胱癌和23例癌旁组织（第1数据组）中的表达。分析FN1表达水平与患者肿瘤分级、分期等临床资料的相关性，探讨FN1对患者预后的影响。结果生物信息学和临床标本验证结果显示FN1在肌层浸润性膀胱癌中显著高于表浅性膀胱癌（P〈0．01）。临床样本验证还发现FN1RNA在膀胱癌中显著高于癌旁组织（P〈0．01）；FN1在第1数据组和GSE31684数据组中表浅性和肌层浸润性膀胱癌的高表达率分别为31．O％比67．0％和6．7％比57．7％，差异均有统计意义（P〈0．05）；在无淋巴结转移组和淋巴结转移组的高表达率分别为27．8％比71．4％和27．7％比64．0％，差异均有统计意义（P〈0．05）；GSE31684数据组中，FN1在复发组和无复发组高表达率为63．9％和40．4％，差异有统计学意义（P〈0．05）；此外，FN1高表达比低表达的患者无复发生存时间缩短（P〈0．05）并且总生存时间显著减少（P〈0．01）；多因数分析结果显示FN1是预测膀胱癌患者总生存时间的独立危险因素（相对危险度=1．724，95％可信区间：1．00—2．96，P〈0．05）。结论FN1在膀胱癌中高表达，FN1高表达预示预后不良，提示FN1可作为判断膀胱癌患者预后的生物标志物。Objective To investigate the expression of fibronectin 1 （FN1） in bladder cancer and explore its clinical significance. Methods Four gene microarray datasets of bladder cancer were downloaded from Gene expression omnibus （GEO）. Microarrays with 55 superficial bladder cancer and 132 muscle -in- vasive bladder cancer tissues were used for analysis of FN1 expression. 59 bladder cancer specimens and 23 adjacent tissues （ cohort 1 ） were used to validate FN1 expression by real - time fluorescent quantitative pol- ymerase chain reaction （ FQ - PCR）. The correlation of FN1 expression with clinical features was analyzed in patients with bladder cancer. Results Bioinformatics analysis identified that FN1 expression in muscle - invasive bladder cancer tissues was significantly higher than in superficial bladder cancer （ P 〈 0. 01 ）. Our results revealed that the expression of FN1 was remarkably up - regulated in bladder cancer tissues as compared with adjacent non - tumor bladder tissues detected by FQ - PCR （P 〈 O. 01 ）, and the expression of FN1 was higher in muscle - invasive bladder cancer than in superficial bladder cancer （P 〈 0.01 ）. Meanwhile, the expression of FN1 was associated with clinical stage （31.0% vs. 67.0%, P 〈 O. 05 for cohort 1 and 6. 7% vs. 57. 7%, P 〈 0.05 for cohort GSE31684） and lymph node metastasis （27.8% vs. 71.4% ,P 〈0.05 for cohort 1 and 64. 0% vs. 27.7% ,P 〈0.05 for cohort GSE31684）. In GSE31684 cohort, the expression of FN1 RNA in recurrent eases was higher than in recurrence - free cases （63.9% vs. 40. 4% ,P 〈0. 05）. More importantly, patients with high expression levels of FN1 had a shorter overall survival （ OS ,P 〈 0. 05 ） and disease - free survival （ P 〈 O. 05 ） time than those with low expression. Univariate and multivariate analysis showed that FN1 was a significant and independent prognostic predictor for OS of patients with bladder cancer （ hazard ratio = 1. 724, 95% C1 = 1.004 - 2. 958, P 〈 0. 05 ）. Conclu- s

关 键 词：膀胱癌 纤维连接蛋白1 预后 

分 类 号：R737.14[医药卫生—肿瘤]