DEP结构域蛋白1B在肝细胞癌中的表达及功能  

Expression and function of DEP domain-containing protein 1B in hepatocellular carcinoma

作　　者：夏辉[1] 戴斌 冉君[2] 王威[1] 龚昭[1] 周程[1] Hui Xia;Bin Dai;Jun Ran;Wei Wang;Zhao Gong;Cheng Zhou(Department of Hepatobiliary Surgery,First Hospital of Wuhan,Wuhan 430000,China;Department of Radiology,Tongji Hospital,Tongji Medical College of Huazhong University of Science and Technology,Wuhan 430000,China)

机构地区：[1]武汉市第一医院肝胆外科,430000 [2]华中科技大学同济医学院附属同济医院放射科,武汉430000

出　　处：《中华肝脏外科手术学电子杂志》2024年第2期205-213,共9页Chinese Journal of Hepatic Surgery(Electronic Edition)

基　　金：湖北省自然科学基金(2022CFB980);武汉市卫生健康委员会医学科研项目(WZ21Q11)。

摘　　要：目的:探讨DEP结构域蛋白1B(DEPDC1B)在肝细胞癌(肝癌)中的表达及功能。方法:检索公共癌症数据库(UALCAN、HPA)分析DEPDC1B在肝癌中的表达;从癌症基因组图谱(TCGA)数据库()获得肝癌的RNAseq数据(level3)和相应的临床信息,Log-rank用于检验Kaplan-Meier生存分析比较上述两组或多组之间的生存差异;单因素及多因素Cox分析DEPDC1B的预后价值并构建列线图。利用siRNA抑制DEPDC1B表达,通过Transwell小室实验检测细胞侵袭、迁移变化;利用STRING构建DEPDC1B蛋白质相互作用网络(PPI)并分析其在肝癌中潜在作用机制。结果:肝癌组织中DEPDC1B基因表达量明显高于正常组织(P<0.05)。肝癌DEPDC1B蛋白的阳性表达率为70%,在20种常见癌症的阳性表达率中排名第一。TCGA数据分析显示,DEPDC1B高表达肝癌患者总体生存期和无病生存期均较差(HR=1.673,1.434;P<0.05),其可作为肝癌的独立预后因子且能效预测患者生存率。Transwell小室实验结果显示,siRNA能明显抑制MHCC97-H、Hep3B肝癌细胞DEPDC1Bb表达;下调DEPDC1B表达后,肿瘤细胞的侵袭及迁移能力减弱。PPI网络构建分析显示,DEPDC1B与TsC/mTOR、RTK、RAS/MAPK、PI3K/AKT、雌激素受体、雄激素受体、上皮间质转化、DNA损伤反应、细胞周期和细胞凋亡等肿瘤标志性信号通路密切相关。结论:DEPDC1B在肝癌中高表达,其高表达与患者预后差相关,下调其表达肝癌细胞侵袭迁移能力下降。Objective To investigate the expression and function of DEP domain-containing protein 1B(DEPDC1B)in hepatocellular carcinoma(HCC).Methods Public cancer databases(UALCAN,HPA)were searched to analyze the expression profile of DEPDC1B in HCC.RNAseq data(level 3)and corresponding clinical information of HCC were obtained from The Cancer Genome Atlas(TCGA)(https://portal.gdc.com).Kaplan-Meier survival analysis was performed using Log-rank test to compare the survival differences between two groups or among multiple groups.Prognostic value of DEPDC1B was assessed by using univariate and multivariate Cox analysis and the nomogram was established.The expression of DEPDC1B was inhibited by siRNA.The changes of cell invasion and migration were detected by Transwell chamber assay.Protein-protein interaction(PPI)of DEPDC1B was constructed by using STRING and the underlying mechanism in HCC was unraveled.Results The expression level of DEPDC1B gene in HCC tissues was significantly higher than that in normal tissues(P<0.05).The positive expression rate of DEPDC1B protein in HCC was 70%,ranking the first among 20 common cancers.TCGA data analysis showed that the overall survival and disease-free survival of HCC patients with high DEPDC1B expression were poor(HR=1.673,1.434;P<0.05),which could be utilized as an independent prognostic factor of HCC and effectively predict the survival rate of HCC patients.Transwell chamber assay revealed that siRNA could significantly inhibit the expression levels of DEPDC1Bb in MHCC97-H and Hep3B cells.After down-regulating the expression of DEPDC1B,the invasion and migration capabilities of tumor cells were weakened.PPI network showed that DEPDC1B was intimately associated with tumor signaling pathways,such as TsC/mTOR,RTK,RAS/MAPK,PI3K/AKT,estrogen receptor,androgen receptor,epithelial-mesenchymal transition,DNA damage response,cell cycle and apoptosis,etc.Conclusions DEPDC1B is highly expressed in HCC.High expression of DEPDC1B is correlated with poor prognosis of HCC patients.Down-regulating

关 键 词：癌 肝细胞 DEP结构域蛋白1B 预后 侵袭 迁移 

分 类 号：R735.7[医药卫生—肿瘤]