分泌型卷曲相关蛋白4在肝细胞癌中的表达及其与患者临床病理指标和预后的关系  

Expression of secreted frizzled-related protein 4 in hepatocellular carcinoma,and relationship with clinicopathological index and prognosis

作　　者：朱文标 闫春梅 丘波[2] 谢寿城 肖焕钦 刘高敏 ZHU Wenbiao;YAN Chunmei;QIU Bo;XIE Shoucheng;XIAO Huanqin;LIU Gaomin(Department of Pathology,Meizhou Clinical Institute of Shantou University Medical College/Meizhou People's Hospital,Meizhou 514031;Molecular Biology Laboratory/Department of Pathology,Jiaying University,Meizhou 514031;Department of Hepatobiliary Surgery,Meizhou Clinical Institute of Shantou University Medical College/Meizhou People's Hospital,Meizhou 514031,Guangdong,China)

机构地区：[1]汕头大学医学院梅州临床学院/梅州市人民医院病理科,广东梅州514031 [2]嘉应学院医学院分子生物学中心实验室/病理教研室,广东梅州514031 [3]汕头大学医学院梅州临床学院/梅州市人民医院肝胆外科,广东梅州514031

出　　处：《癌变．畸变．突变》2024年第4期288-293,297,共7页Carcinogenesis,Teratogenesis & Mutagenesis

基　　金：广东省医学科研基金(B2021140);梅州市人民医院科研培育项目(PY-C2020008)。

摘　　要：目的:探讨分泌型卷曲相关蛋白4(sFRP4)在肝细胞癌(HCC)中的表达及其与患者临床病理指标和预后的关系。方法:免疫组织化学法检测95例手术切除的HCC组织及癌旁组织中sFRP4蛋白的表达,分析sFRP4蛋白表达水平与患者临床病理指标及预后的关系,Cox比例风险回归模型分析影响HCC患者预后的因素。结果:sFRP4蛋白在HCC组织中的阳性表达率为48.42%(46/95),在癌旁组织中的阳性表达率为85.26%(81/95),sFRP4蛋白在HCC组织中的阳性表达率低于癌旁组织(χ^(2)=24.596;P<0.01)。sFRP4蛋白在不同组织学分级(χ^(2)=11.877,P<0.05)、组织学亚型(χ^(2)=3.873,P<0.05)及微血管侵犯(χ^(2)=6.493,P<0.05)的HCC组织中表达水平差异有统计学意义,s FRP4蛋白阴性组患者累积总生存期(OS)和累积无病生存期(PFS)显著短于阳性组(均为P<0.01)。多因素分析显示sFRP4蛋白表达水平[HR=0.238,95%CI(0.138,0.412),P<0.01]、中国肝癌临床分期[HR=2.438,95%CI(1.256,4.730),P<0.01]是影响HCC患者手术切除后PFS的独立风险因素,sFRP4蛋白表达水平[HR=0.226,95%CI(0.109,0.467),P<0.01]、组织学分级[HR=2.236,95%CI(1.199,4.170),P<0.05]是影响HCC患者手术切除后OS的独立风险因素。结论:sFRP4蛋白在HCC组织及癌旁组织中,以及不同病理特征的HCC组织中表达水平有差异,sFRP4蛋白阴性组患者预后较差,sFRP4蛋白表达水平是HCC患者手术切除后预后的独立风险因素。OBJECTIVE:To investigate expression of secreted frizzled-related protein 4(sFRP4)in hepatocellular carcinoma(HCC)and relationship with clinicopathological index and prognosis.METHODS:Immunohistochemical methods were used to detect the expression of sFRP4 protein in 95 surgically resected HCC tissues and paracancerous tissues;patients clinicopathological indexes were used to analyze relationships with expression levels of the sFRP4 protein;the Kaplan-Meier survival curves were used to analyze relationships between expression of the sFRP4 protein and prognosis of the patients based on their clinicopathological index;and proportional hazards model(COX)was used to analyze factors affecting the prognosis of HCC patients.RESULTS:The positivity rate of sFRP4 protein was 48.42%(46/95)in HCC tissues and 85.26%(81/95)in paracancerous tissues.sFRP4 protein was therefore less positive in HCC tissues than in paracancerous tissues(χ^(2)=24.596,P<0.01).Its expression in HCC tissues were significant for different histological grade(χ^(2)=11.877,P<0.05),histological subtype(χ^(2)=3.873,P<0.05)and microvascular invasion(χ^(2)=6.493,P<0.05).Patients with the sFRP4 protein-negativity had significantly worse cumulative overall survival(OS)and cumulative disease-free survival(PFS)than that of the positive group(both P<0.01).Cox multivariate analysis showed that sFRP4 protein[HR=0.238,95%CI(0.138,0.412),P<0.01],clinical stage of hepatocellular carcinoma in China[HR=2.438,95%CI(1.256,4.730),P<0.01]were independent risk factors affecting the PFS after surgical resection of HCC.In addition,the sFRP4 protein[HR=0.226,95%CI(0.109,0.467),P<0.01]and histological grade[HR=2.236,95%CI(1.199,4.170),P<0.05]were independent risk factors affecting the OS after surgical resection of HCC.CONCLUSION:Expression levels of the sFRP4 protein were differentially significant between the HCC and paracancerous tissues,as well as with histological grade,histological subtype and microvascular invasion in HCC tissues.The sFRP4 protein-negative group of patie

关 键 词：肝细胞癌 分泌型卷曲相关蛋白4 临床病理指标 预后 

分 类 号：R730.2[医药卫生—肿瘤]