Ⅲ型纤维连接蛋白结构域蛋白3B在胰腺癌组织的表达及其临床意义  

The expression and clinical significance of fibronectin typeⅢdomain containing 3B in pancreatic cancer

作　　者：沈雁兵 马丹丹 李中虎 尚作宏 林振宇 钟彬 张建新 金炜东 Shen Yanbing;Ma Dandan;Li Zhonghu;Shang Zuohong;Lin Zhenyu;Zhong Bin;Zhang Jianxin;Jin Weidong(Department of General Surgery,General Hospital of Central Theater Command of PLA,Wuhan 430070,China)

机构地区：[1]中国人民解放军中部战区总医院普通外科,武汉430070

出　　处：《中华实验外科杂志》2021年第11期2239-2242,共4页Chinese Journal of Experimental Surgery

基　　金：国家自然科学基金项目(81902501)。

摘　　要：目的探讨Ⅲ型纤维连接蛋白结构域蛋白3B(FNDC3B)在胰腺癌中的表达差异与临床病理特征和预后的关系,并探讨其可能发生相互作用的蛋白网络及其在胰腺癌发生发展中调控的可能信号通路。方法采用蛋白质印迹法(Western blot)检测FNDC3B在胰腺癌组织及癌旁组织中的蛋白表达差异,用GEPIA分析FNDC3B在胰腺癌组织及正常胰腺组织中的mRNA表达差异。在癌症基因组图谱(TCGA)数据库获取胰腺癌病例资料,利用SPSS 25.0分析FNDC3B表达差异与胰腺癌患者临床病理特征和预后的关系。采用Kaplan-Meier法绘制胰腺癌患者生存曲线。STRING数据库分析与FNDC3B相互作用的蛋白网络。基因集富集分析(GSEA)预测FNDC3B在胰腺癌中调控的可能信号通路。计数资料比较采用χ^(2)检验,单因素及多因素分析采用COX回归分析,组间比较采用t检验。结果 Western blot检测结果显示FNDC3B在胰腺癌组织中的蛋白表达量高于癌旁组织(1.038±0.103比0.341±0.027,t=22.807,P<0.01)。GEPIA数据库分析结果显示FNDC3B在胰腺癌组织中的mRNA表达量高于正常胰腺组织(P均<0.05)。FNDC3B基因表达水平与胰腺癌患者的年龄(χ^(2)=12.115,P<0.01)、病理分级(χ^(2)=11.490,P<0.01)和N分期(χ^(2)=3.962,P<0.05)密切相关,与性别、病理分期、T分期、M分期无明显相关(P均>0.05)。单因素Cox分析结果显示N分期[风险比(HR)=2.001,95%可信区间(CI)=1.193~3.354,P<0.01]和FNDC3B mRNA表达水平(HR=1.595,95%CI=1.051~2.421,P<0.05)对胰腺癌患者的预后存在显著影响。多因素Cox分析结果显示FNDC3B mRNA表达水平(HR=1.565,95%CI=1.011~2.423,P<0.05)是胰腺癌患者预后的独立危险因素。FNDC3B高表达组胰腺癌患者的生存时间显著低于FNDC3B低表达组患者(χ^(2)=4.898,P<0.05,中位生存时间为592 d比634 d)。STRING数据库分析结果表明,与FNDC3B相互作用蛋白有FAM46A(分值=0.687)、ZNF469(分值=0.672)、B3GNT7(分值=0.647)等。GSEA研究结果�Objective To investigate the expression of fibronectin typeⅢdomain containing 3B(FNDC3B)in pancreatic cancer and its association with clinicopathological features and prognosis.And to predict the interactions protein network and the possible signal pathways of FNDC3B in pancreatic cancer.Methods Western blotting was used to analyze the FNDC3B protein expression difference between pancreatic cancer tissues and adjacent normal tissues.Meanwhile,the mRNA expression difference of FNDC3B between pancreatic cancer tissues and pancreatic tissues were analyzed by GEPIA.The pancreatic cancer dataset was collected from the Cancer Genome Atlas(TCGA)database.Statistic software SPSS 25.0 was used to analyze the correlation between expression level of FNDC3B and clinicopathological features and prognosis of pancreatic cancer patients.The survival curve of pancreatic cancer patients was analyzed by Kaplan-Meier method.The STRING database was used to analyze the network of proteins interacting with FNDC3B.Gene set enrichment analysis(GSEA)was used to predict the possible signal pathways of FNDC3B in pancreatic cancer.Results Western blotting results showed that FNDC3B protein expression in pancreatic cancer tissues was higher than in adjacent tissues(1.038±0.103 vs.0.341±0.027,t=22.807,P<0.01).While,GEPIA results showed that FNDC3B mRNA expression in pancreatic cancer tissues was higher than in normal pancreatic tissues(P all<0.05).And FNDC3B mRNA expression level was associated with age(χ^(2)=12.115,P<0.01),pathological grade(χ^(2)=11.490,P<0.01)and N stage(χ^(2)=3.962,P<0.05),not with gender,pathological stage,T stage,M stage(P all<0.05).Univariate Cox analysis results showed that N stage[hazard ratio(HR)=2.001,95%confidence interval(CI)=1.193-3.354,P<0.01]and FNDC3B mRNA expression level(HR=1.595,95%CI=1.051-2.421,P<0.05)were correlated with the prognosis of pancreatic cancer patients.Results of multivariate Cox analysis showed that FNDC3B mRNA expression level(HR=1.565,95%CI=1.011-2.423,P<0.05)was independent factors

关 键 词：Ⅲ型纤维连接蛋白结构域蛋白3B 胰腺癌 表达 临床意义 

分 类 号：R735.9[医药卫生—肿瘤]