肝细胞癌生物标志物识别及靶向中药预测*
作者：袁 媛1，张睿添2，秦秋云3，李妞妞3，夏 猛3，李相玲4，张 萌3
单位：1.广西中医药大学公共卫生与管理学院，广西 南宁 530200； 2.广西中医药大学壮医药学院，广西 南宁 530200； 3.广西中医肝脾藏象重点研究室，广西 南宁 530200； 4.广西中医药大学中医药壮瑶医药研究院，广西 南宁 530200
引用：引用：袁媛，张睿添，秦秋云，李妞妞，夏猛，李相玲，张萌.肝细胞癌生物标志物识别及靶向中药预测[J].中医药导报,2025,31(7):195-203.
DOI：10.13862/j.cn43-1446/r.2025.07.032
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摘要：
目的：发掘肝细胞癌（HCC）生物标志物，并预测其靶向中药及活性成分，以期为HCC提供新的治疗策略及用药参考。方法：在TCGA（癌症基因组图谱）数据库肝癌数据集中筛选差异基因，通过加权基因共表达网络分析（WGCNA）确定关键模块基因。利用京都基因与基因组百科全书（KEGG）和基因本体（GO）富集分析揭示其生物学功能。使用机器学习算法评估生物标志物的诊断效能、染色体定位及单细胞特征。采用CIBERSORT算法分析免疫细胞浸润情况。利用中药系统药理学数据库和分析平台（TCMSP）预测生物标志物潜在靶向中药及其活性成分。结果：关键模块基因KEGG通路富集在细胞周期、细胞衰老等信号通路。筛选出MDK（中期因子）、RASGRF2（Ras鸟苷酸释放因子2）、CYP2C9（细胞色素P4502C9酶）、TERT（端粒逆转录酶）、LCAT（卵磷脂胆固醇酰基转移酶）和ADRA2B（α2B肾上腺素能受体）共6种生物标志物。免疫细胞浸润分析显示，活化记忆CD4+T细胞、T滤泡辅助细胞、M0巨噬细胞、静息肥大细胞等在HCC发生机制中与上述标志物密切相关。中药预测结果表明，包括洋金花、延胡索和华山参在内的48种中药及其57种活性成分可能作为潜在治疗手段。结论：MDK、RASGRF2、CYP2C9、TERT、LCAT和ADRA2B通过影响免疫细胞浸润参与HCC发生发展，可作为HCC的生物标志物。中医药及其活性成分能通过调控这些关键基因发挥治疗作用，为HCC提供了新的治疗策略和用药参考。
关键词：肝细胞癌；生物信息学；生物标志物；免疫细胞浸润；中药预测
Abstract：Objective: To identify hepatocellular carcinoma (HCC)
biomarkers and predict their targeted traditional Chinese medicine (TCM) and
active components, aiming to provide new therapeutic strategies and medication
references for HCC. Methods: Differential genes were screened from the liver
cancer dataset in The Cancer Genome Atlas (TCGA) database, and key module genes
were identified through weighted gene co-expression network analysis (WGCNA).
Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO)
enrichment analyses were used to reveal their biological functions. Machine learning
algorithms were applied to evaluate the diagnostic efficacy, chromosomal
localization, and single-cell characteristics of the biomarkers. The CIBERSORT
algorithm was used to analyze immune cell infiltration. The Traditional Chinese
Medicine Systems Pharmacology Database and Analysis Platform (TCMSP) was
utilized to predict potential targeted TCM and their active components for the
biomarkers. Results: The key module gene KEGG pathway is enriched in signaling
pathways such as the cell cycle and cell senescence. Six biomarkers were
screened out, including MDK (midkine), RASGRF2 (Ras guanine nucleotide release
factor 2), CYP2C9 (cytochrome P450 2C9), TERT (telomerase reverse
transcriptase), LCAT (lecithin-cholesterol acyltransferase), and ADRA2B (alpha-2B
adrenergic receptor). Immune cell infiltration analysis showed that activated
memory CD4+ T cells, T follicular helper cells, M0 macrophages, resting mast
cells, etc., were closely related to the above biomarkers in the pathogenesis
of HCC. TCM prediction results indicated that 48 kinds of TCM, including
Yangjinhua (Daturae Flos), Yanhusuo (Corydalis Rhizoma), and Huashanshen
(Physochlainae Radix), along with their 57 active components, might serve as
potential therapeutic agents. Conclusion: MDK, RASGRF2, CYP2C9, TERT, LCAT, and
ADRA2B are involved in the occurrence and development of HCC by affecting
immune cell infiltration and can be used as biomarkers for HCC. TCM and their
active components can exert therapeutic effects by regulating these key genes,
providing new therapeutic strategies and medication references for HCC.
Key words：hepatocellular carcinoma; bioinformatics; biomarkers; immune cell infiltration; traditional Chinese medicine prediction
发布时间：2026-01-06
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