ASTN1表达与肝细胞癌侵袭转移及预后的关系  

Relationship between ASTN1 expression and invasion,metastasis,prognosis of hepatocellular carcinoma

作　　者：陈奇峰 黄涛 沈露俊[1] 李旺[1] 吴沛宏[1] Chen Qifeng;Huang Tao;Shen Lujun;Li Wang;Wu Peihong(Department of Minimally Invasive Intervention,Sun Yat-sen University Cancer Center,State Key Laboratory of Oncology in South China,Collaborative Innovation Center for Cancer Medicine,Guangzhou 510060,China)

机构地区：[1]中山大学肿瘤防治中心微创介入科,华南肿瘤学国家重点实验室,肿瘤医学协同创新中心,广州510060

出　　处：《中华肝脏外科手术学电子杂志》2020年第3期278-282,共5页Chinese Journal of Hepatic Surgery(Electronic Edition)

基　　金：国家自然科学基金(81801804)。

摘　　要：目的探讨星形肌动蛋白1(astrotactin 1,ASTN1)与肝细胞癌(HCC)侵袭转移的关系及其对患者预后的影响。方法从癌症基因组图谱(TCGA)公共数据库下载HCC的RNA表达谱数据和临床信息,比较HCC组织和癌旁对照组织ASTN1 mRNA的表达水平。ASTN1 mRNA在癌与癌旁组织差异分析采用Wilcoxon符号秩和检验。根据ASTN1表达高低绘制Kaplan-Meier生存曲线,两组生存分析采用Log-rank检验。Cox比例风险回归模型分析ASTN1的表达与预后的关系。采用siRNA技术沉默HCC细胞中的ASTN1基因,Transwell小室检测细胞侵袭能力的变化,细胞划痕实验检测细胞迁移能力的变化。穿膜细胞数比较采用单因素方差分析和LSD-t检验。结果HCC组织ASTN1 mRNA相对表达量为0.022(0~0.137),明显低于癌旁组织的0.037(0.004~0.216)(Z=-12.297,P<0.05)。生存分析显示ASTN1高表达组患者的总体生存预后更好(HR=0.480,P<0.05)。Cox回归分析显示,ASTN1低表达是影响HCC患者总体生存预后的独立危险因素(HR=1.852,95%CI:1.635~2.313,P<0.05)。Transwell侵袭实验显示,siRNA-1和siRNA-2组穿膜细胞数为(88±7)、(89±5)个,明显高于对照组的(38±3)个(LSD-t=11.720,15.150;P<0.05)。细胞划痕实验显示,沉默ASTN1基因后细胞的侵袭转移能力增强。结论ASTN1高表达是影响HCC患者总体生存预后的独立保护因素,ASTN1低表达患者预后更差。ASTN1可作为判断HCC患者生存预后的生物学标志物。Objective To investigate the relationship between astrotactin 1(ASTN1)and the invasion,metastasis of hepatocellular carcinoma(HCC)and its effect on clinical prognosis of HCC patients.Methods RNA expression profile data and clinical information of HCC were downloaded from The Cancer Genome Atlas(TCGA)public database.The expression levels of ASTN1 mRNA in the liver cancer tissues and paracancerous tissues were statistically compared by Wilcoxon signed rank sum test.Kaplan-Meier survival curve was delineated according to the expression level of ASTN1.The survival analysis between two groups was analyzed by Log-rank test.The relationship between ASTN1 expression and prognosis was assessed by Cox's proportional hazards regression model.ASTN1 gene in the HCC cells was silenced by siRNA technology.The change of cell invasion ability was evaluated by Transwell chamber test.The change of cell migration ability was assessed by cell scratch test.The number of membrane-penetrating cells was compared by one-way analysis of variance and LSD-t test.Results The relative expression level of ASTN1 mRNA in the HCC tissues was 0.022(0-0.137),significantly lower than 0.037(0.004-0.216)in the paracancerous tissues(Z=-12.297,P<0.05).Survival analysis demonstrated that patients with high ASTN1 expression obtained better overall survival(HR=0.480,P<0.05).Cox's proportional hazards model showed that the low expression of ASTN1 was an independent risk factor for the overall survival of HCC patients(HR=1.852,95%CI:1.635-2.313,P<0.05).Transwell chamber demonstrated that the number of membranepenetrating cells in siRNA-1 and siRNA-2 groups was respectively 88±7 and 89±5,significantly higher than 38±3 in control group(LSD-t=11.720,15.150;P<0.05).Cell scratch test revealed that the invasion and metastasis ability of cells was enhanced after the silencing of ASTN1 gene.Conclusions High expression of ASTN1 is an independent protective factor for the overall survival of HCC patients.Patients with low expression of ASTN1 obtain poor clinical pro

关 键 词：癌 肝细胞 ASTN1 预后 生物学标志物 

分 类 号：R735.7[医药卫生—肿瘤]