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

doi:10.3969/j.issn.1004-616x.2024.04.007

癌变·畸变·突变 ›› 2024, Vol. 36 ›› Issue (4): 288-293,297.doi: 10.3969/j.issn.1004-616x.2024.04.007

• 论著 • 上一篇

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

朱文标¹, 闫春梅¹, 丘波², 谢寿城¹, 肖焕钦¹, 刘高敏³

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

收稿日期:2024-04-16 修回日期:2024-06-11 发布日期:2024-08-06
通讯作者: 刘高敏
作者简介:朱文标，E-mail：piaoran7907@126.com。
基金资助:
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)

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

ZHU Wenbiao¹, YAN Chunmei¹, QIU Bo², XIE Shoucheng¹, XIAO Huanqin¹, LIU Gaomin³

1. Department of Pathology, Meizhou Clinical Institute of Shantou University Medical College/Meizhou People's Hospital, Meizhou 514031;
2. Molecular Biology Laboratory/Department of Pathology, Jiaying University, Meizhou 514031;
3. Department of Hepatobiliary Surgery, Meizhou Clinical Institute of Shantou University Medical College/Meizhou People's Hospital, Meizhou 514031, Guangdong, China

Received:2024-04-16 Revised:2024-06-11 Published:2024-08-06

摘要/Abstract

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(χ²=24.596；P<0.01)。sFRP4蛋白在不同组织学分级(χ²=11.877，P<0.05)、组织学亚型(χ²=3.873，P<0.05)及微血管侵犯(χ²=6.493，P<0.05)的HCC组织中表达水平差异有统计学意义，sFRP4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。

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

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 (χ²=24.596，P<0.01). Its expression in HCC tissues were significant for different histological grade (χ²=11.877，P<0.05)，histological subtype (χ²=3.873，P<0.05) and microvascular invasion (χ²=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.

Key words: hepatocellular carcinoma, secreted frizzled-related protein 4, clinicopathological index, prognosis

中图分类号:

R730.2

朱文标, 闫春梅, 丘波, 谢寿城, 肖焕钦, 刘高敏. 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[J]. 癌变·畸变·突变, 2024, 36(4): 288-293,297.

ZHU Wenbiao, YAN Chunmei, QIU Bo, XIE Shoucheng, XIAO Huanqin, LIU Gaomin. Expression of secreted frizzled-related protein 4 in hepatocellular carcinoma, and relationship with clinicopathological index and prognosis[J]. Carcinogenesis, Teratogenesis & Mutagenesis, 2024, 36(4): 288-293,297.

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

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