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中国癌症防治杂志

中国癌症防治杂志 ›› 2025, Vol. 17 ›› Issue (2): 180-187.doi: 10.3969/j.issn.1674-5671.2025.02.07

• 论著 • 上一篇    下一篇

纤维化相关的RBP4蛋白作为肝细胞癌生物标志物的研究

  

  1. 广西医科大学公共卫生学院;广西医科大学实验动物中心；区域性高发肿瘤早期防治研究教育部重点实验室（广西医科大学）;靶向肿瘤学国家重点实验室
  • 出版日期:2025-04-25 发布日期:2025-05-15
  • 通讯作者: 何敏 E-mail：hemin@gxmu.edu.cn
  • 基金资助:
    广西重点研发项目（AB24010127）

FAM50A  gene  knockdown suppresses malignant biological behaviors of colorectal cancer cells via the Caspase-3/PARP-mediated apoptotic signaling

  • Online:2025-04-25 Published:2025-05-15

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摘要： 目的 探讨视黄醇结合蛋白4（retinol⁃binding protein 4，RBP4）在肝细胞癌（hepatocellular carcinoma，HCC）与肝纤维化(liver fibrosis，LF)中的表达特征及其临床意义。 方法 通过TCGA数据库分析RBP4在HCC中的表达水平及其与临床病理特征和预后的关系；多反应监测（multi⁃response monitoring, MRM）质谱技术对24例HCC患者、10例慢性乙型肝炎(chronic hepatitis B，CHB)患者、10例LF患者和13名健康对照者(health control，HC)血清中RBP4蛋白进行定量；杂交瘤的方式制备高纯度抗RBP4单克隆抗体，应用该抗体对11例HCC患者肝组织中RBP4的蛋白表达进行免疫组化法（immunohistochemistry，IHC）检测。 结果 TCGA数据集分析结果显示，肝癌组织中RBP4表达水平较正常肝组织显著降低（P<0.0001）；RBP4表达水平与肝癌临床分期、病理分级及人种有关（均P<0.05）；RBP4高表达HCC患者的预后显著优于低表达患者（均P<0.05）。血清MRM质谱检测结果显示，HCC及LF组RBP4蛋白含量均较HC组及CHB组显著降低（均P<0.001）。制备的高纯度抗RBP4单克隆抗体效价高达1∶729 000，且能特异性识别RBP4蛋白。IHC检测结果显示，RBP4在HCC组织及LF组织中的表达水平均较HCC癌旁组织显著降低（均P<0.0001），且在LF组织中的表达水平显著低于HCC组织（P<0.05）。 结论 相较于正常组织，RBP4在HCC和LF组织中低表达，且与患者预后不良及纤维化进展有关。

关键词: 肝细胞癌, 视黄醇结合蛋白4, 单克隆抗体, 肝纤维化

Abstract: Objective To explore the expression characteristics of retinol⁃binding protein 4 (RBP4) in hepatocellular carcinoma (HCC) and liver fibrosis (LF), as well as its clinical significance. Methods The TCGA database was used to analyze the expression level of RBP4 in HCC and its relationship with clinicopathological characteristics and prognosis. Multi⁃response monitoring (MRM) mass spectrometry was used to quantify the serum RBP4 protein expression in 24 HCC patients, 10 chronic hepatitis B (CHB) patients, 10 LF patients and 13 healthy control (HC) population. A high⁃purity anti⁃RBP4 monoclonal antibody was prepared by hybridoma, and the protein expression level of RBP4 protein in the liver tissues of 11 HCC patients was detected by immunohistochemistry (IHC).  Results The results of TCGA dataset analysis showed that the expression levels of RBP4 protein level in HCC tissues were significantly reduced compared to normal liver tissues (P<0.0001). RBP4 expression correlated with the stage, pathological grade and ethnicity (all P<0.05). The prognosis of HCC patients with high RBP4 expression was significantly better than that of patients with low RBP4 expression (all P<0.05). The results of serum MRM mass spectrometry showed that serum RBP4 protein level in HCC and LF groups were significantly lower than those in the HC and CHB groups (all P<0.001). The high⁃purity anti⁃RBP4 monoclonal antibody was prepared with a titer of 1∶729 000 and could specifically recognize RBP4 protein. The results of IHC showed that the expression levels of RBP4 in HCC tissues and LF tissues were significantly lower than that in adjacent tissues (all P<0.0001), in LF tissues were significantly lower than that in HCC tissues (P<0.05). Conclusions Compared with normal tissues, RBP4 is downregulated in HCC and LF tissues, and is associated with poor prognosis and fibrotic progression. 

Key words: Hepatocellular carcinoma, RBP4, Monoclonal antibody, Liver fibrosis

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