Wang Yanping, Wang Huan, Wei Shuai, Gao Zhiliang, Gao Haili, Wang Xinwei, Liang Haijun, Yang Daokun
Department of Infectious Diseases, The First Affiliated Hospital of Xinxiang Medical University, Xinxiang, Henan.
Department of Pharmacy, The Fifth Medical Center of Chinese PLA General Hospital, Beijing.
Eur J Gastroenterol Hepatol. 2025 Sep 1;37(9):1040-1048. doi: 10.1097/MEG.0000000000003021. Epub 2025 Jul 30.
Chronic hepatitis B virus (HBV) infection can increase the risk of developing liver cirrhosis (LC) and hepatocellular carcinoma (HCC). Timely detection of precancerous lesions for patients with chronic HBV infection is critical in preventing worse consequences. The purpose of this study is to reveal the key serum metabolic biomarkers that can be applied to the early recognition of HCC in patients with HBV-associated cirrhosis.
Blood samples from patients with LC, HCC, and healthy subjects were collected, and endogenous metabolites in serum were detected by ultra high performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UHPLC-Q-TOF/MS). Differential metabolites (DM) were screened, and metabolic pathways and Kyoto Encyclopedia of Genes and Genomes signals involved in DM were analyzed.
Metabolomics results revealed that patients with LC and HCC had significantly different metabolic characteristics. Patients with LC and HCC shared 22 biomarkers, LC had six different biomarkers, and HCC had 10 different biomarkers. The expressions of these metabolites all showed significant differences between groups. Pathway enrichment analysis revealed that the differential biomarkers of LC were primarily involved in the regulation of phospholipid biosynthesis, while the differential biomarkers of HCC were mainly involved in the regulation of endogenous androgen signaling, mitochondrial fatty acid metabolism, and purine metabolism signaling. The common biomarkers are enriched in bile acid metabolism, amino acid metabolism, and arachidonic acid metabolism.
We clarified the blood metabolism characteristics of LC and HCC. These findings provided potential endogenous metabolic indicators for early recognition of HBV-chronically infected cirrhotic patients who may progress to HCC.
慢性乙型肝炎病毒（HBV）感染会增加发生肝硬化（LC）和肝细胞癌（HCC）的风险。及时检测慢性HBV感染患者的癌前病变对于预防更严重的后果至关重要。本研究的目的是揭示可用于早期识别HBV相关性肝硬化患者HCC的关键血清代谢生物标志物。
收集LC、HCC患者及健康受试者的血液样本，采用超高效液相色谱-四极杆飞行时间质谱（UHPLC-Q-TOF/MS）检测血清中的内源性代谢物。筛选差异代谢物（DM），并分析DM涉及的代谢途径和京都基因与基因组百科全书信号。
代谢组学结果显示，LC和HCC患者具有显著不同的代谢特征。LC和HCC患者共有22种生物标志物，LC有6种不同的生物标志物，HCC有10种不同的生物标志物。这些代谢物的表达在各组之间均显示出显著差异。通路富集分析显示，LC的差异生物标志物主要参与磷脂生物合成的调节，而HCC的差异生物标志物主要参与内源性雄激素信号传导、线粒体脂肪酸代谢和嘌呤代谢信号传导的调节。共同的生物标志物富集于胆汁酸代谢、氨基酸代谢和花生四烯酸代谢。
我们阐明了LC和HCC的血液代谢特征。这些发现为早期识别可能进展为HCC的慢性HBV感染肝硬化患者提供了潜在的内源性代谢指标。
