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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 4in hepatocellular carcinoma,and relationship with clinicopathological index and prognosis

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【作者】 朱文标闫春梅丘波谢寿城肖焕钦刘高敏

【Author】 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;Molecular Biology Laboratory/Department of Pathology,Jiaying University;Department of Hepatobiliary Surgery,Meizhou Clinical Institute of Shantou University Medical College/Meizhou People’s Hospital;

【通讯作者】 刘高敏;

【机构】 汕头大学医学院梅州临床学院/梅州市人民医院病理科嘉应学院医学院分子生物学中心实验室/病理教研室汕头大学医学院梅州临床学院/梅州市人民医院肝胆外科

【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。

【Abstract】 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 patients had a poorer prognosis.In addition,its expression level was an independent risk factor for the prognosis of these patients after surgical resection.

【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)
  • 【文献出处】 癌变·畸变·突变 ,Carcinogenesis,Teratogenesis & Mutagenesis , 编辑部邮箱 ,2024年04期
  • 【分类号】R735.7
  • 【下载频次】9
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