卡培他滨相关代谢酶在肝细胞癌中的差异表达及其临床价值：一项回顾性队列研究

Differential expression of capecitabine-related metabolic enzymes in hepatocellular carcinoma and its clinical value: a retrospective cohort study.

作者信息

Lu Jianing, Yin Zhiqi, Zhuang Yan, Wang Zhenglu, Zheng Hong, Cao Lei, Kong Dejun, Duan Jinliang, Chen Shaofeng, Chen Tao

机构信息

The First Central Clinical College, Tianjin Medical University, No. 24 Fukang Road, Nankai District, Tianjin, 300070, China.

Department of Pathology, Tianjin First Central Hospital, First Central Clinical College, Tianjin Medical University, No. 24 Fukang Road, Nankai District, Tianjin, 300192, China.

出版信息

Discov Oncol. 2025 Jun 12;16(1):1066. doi: 10.1007/s12672-025-02807-6.

DOI:10.1007/s12672-025-02807-6

PMID:40504344

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12162402/

Abstract

BACKGROUND

Capecitabine (CAP) is widely used in cancer treatment for its oral convenience and tumor targeting. However, its effectiveness in hepatocellular carcinoma (HCC) is suboptimal, possibly due to metabolic enzyme expression differences. This study aims to analyze these enzymes' expression differences and explore their correlation with clinical pathological factors, to inform personalized CAP treatment.

METHODS

This retrospective study used Immunohistochemistry (IHC) to analyze tumor and non-tumorous samples from HCC patients for CAP metabolic enzyme expression. PRM protein quantification was performed on 10% of samples to validate IHC results. Clinical and pathological data were collected, and multivariable linear regression was used to identify independent risk factors.

RESULTS

This study analyzed 60 HCC patients with hepatitis B and cirrhosis, revealing significant differences in CAP metabolic enzymes expression between tumor and non-tumorous tissues, with greater individual differences in tumors. Cytidine deaminase (CDA) levels in tumors decreased as liver function deteriorated (P = 0.023), while thymidine phosphorylase (TP) levels increased (P < 0.001). Tumor tissue had lower levels of carboxylesterase 1-2 (CES1-2), CDA, and dihydropyrimidine dehydrogenase (DPYD) but higher TP levels than non-tumorous and normal liver tissues. In tumor tissue, CDA (CV: 118.70%, SD: 3.897) and CES2 (CV: 94.90%, SD: 2.910) showed the greatest individual variability. Multivariable linear regression identified independent risk factors affecting CAP metabolic enzyme expression.

CONCLUSION

This study has found significant variability in the expression of CAP metabolic enzymes across individuals and tissues. Developing a treatment flowchart based on metabolic enzymes provides a foundation for personalized HCC treatment and enhances the effectiveness of CAP therapy.

CLINICAL TRIAL NUMBER

Not applicable.

摘要

背景

卡培他滨（CAP）因其口服便捷和肿瘤靶向性而广泛应用于癌症治疗。然而，其在肝细胞癌（HCC）中的疗效欠佳，可能是由于代谢酶表达差异所致。本研究旨在分析这些酶的表达差异，并探讨它们与临床病理因素的相关性，以为CAP个性化治疗提供依据。

方法

本回顾性研究采用免疫组织化学（IHC）分析HCC患者的肿瘤和非肿瘤样本中CAP代谢酶的表达。对10%的样本进行PRM蛋白定量以验证IHC结果。收集临床和病理数据，并采用多变量线性回归确定独立危险因素。

结果

本研究分析了60例乙型肝炎和肝硬化的HCC患者，发现肿瘤组织和非肿瘤组织中CAP代谢酶的表达存在显著差异，肿瘤中的个体差异更大。随着肝功能恶化，肿瘤中的胞苷脱氨酶（CDA）水平降低（P = 0.023），而胸苷磷酸化酶（TP）水平升高（P < 0.001）。肿瘤组织中羧酸酯酶1-2（CES1-2）、CDA和二氢嘧啶脱氢酶（DPYD）的水平低于非肿瘤组织和正常肝组织，但TP水平高于它们。在肿瘤组织中，CDA（变异系数：118.70%，标准差：3.897）和CES2（变异系数：94.90%，标准差：2.910）的个体变异性最大。多变量线性回归确定了影响CAP代谢酶表达的独立危险因素。