肝星状细胞分泌因子在乙型肝炎相关肝纤维化/肝硬化诊断中的价值
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Diagnostic value of the factors secreted by hepatic stellate cells in hepatitis B-related liver fibrosis and cirrhosis
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    摘要:目的通过分析单细胞测序数据,明确肝纤维化和肝硬化的相关血清学标志物。方法选取GSE136103数据集,分析肝硬化组患者肝脏组织中的细胞群体改变状况,确定肝星状细胞(HSC)的改变,并在GSE168933数据集中进行验证。检测HSC的信号传入/传出,并对HSC特异性的受体-配体的相对贡献度进行排序,根据前20位的受体-配体结合对,选取相应的细胞因子,并对2019年9月至2021年5月于宁波开发区医院就诊的300例肝病患者进行各项实验室血清学指标检测,构建Logistic回归诊断模型,进一步探讨该模型对肝纤维化和肝硬化的诊断价值。结果在GSE136103与GSE168933数据集中,HSC在肝硬化患者肝脏组织中呈特异性升高;基于受体-配体的相对贡献度,最终得到14种HSC特异性分泌的细胞因子,包括:生长停滞特异性基因6蛋白(Gas6)、第3类半胱氨酸丰富结构域蛋白F(Sema3f)、第3类半胱氨酸丰富结构域蛋白A(Sema3a)等。该特异性细胞因子在诊断肝纤维化+肝硬化时的ROC曲线下面积(AUC)为O.92,单独诊断肝纤维化的AUC为0.89,单独诊断肝硬化的AUC为0.88,而使用FIB-4标准诊断的AUC分别为0.86(仅肝纤维化)、0.86(仅肝硬化)。结论基于单细胞测序数据分析得到的HSC特异性细胞因子,对肝纤维化与肝硬化具有良好的诊断价值,且优于现有的FIB-4标准。

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    Abstract: ObjectiveTo identify the serological biomarkers associated with liver fibrosis and cirrhosis by analyzing single-cell sequencing data. MethodsThe GSE136103 dataset was selected to analyze the changes in cellular populations in liver tissues of the cirrhosis groupand determine the changes in hepatic stellatecells(HSC).Then,the GSE168933dataset was used to validate them.Concurrent- ly,the signal input and output of HSC cells were detected, and the relative contribution of HSC-specific receptor-ligand pairs was ranked. Based on the top 20 receptor-ligand pairs,the corresponding cytokines were selected.Additionally,the serological markers for 300 patients with liver diseases who visited Ningbo Development Zone Hospital from September 2019 to May 2021 were detected. A Logistic regression diagnostic model was constructed, and its diagnostic value in liver fibrosis and cirhosis was further explored. Results In the GSE136103 and GSE168933 datasets, HSCs were specifically elevated in liver tissues of the patients with cirrhosis. Based on the relative contribution of receptor-ligand pairs,14 cytokines specifically secreted by HSCs,including growth arrestspecific protein 6 (Gas6),semaphorin3F (Sema3f),semaphorin3A(Sema3a),and etc.,were ultimately obtained. The area under the ROC curve (AUC) of these specific cytokines in the diagnosis of liver fibrosis and cirrhosis was O.92. The AUC for the diagnosis of liver fibrosis alone and cirrhosis alone were O.89 and O.88, respectively. While,the AUC of the FIB4 criteria in the diagnosis of liver fibrosis alone and cirhosis alone were both O.86. ConclusionThe HSC-specific cytokines obtained from single-cell sequencing data have god diagnostic value for liver fibrosis and cirhosis,which is superior to the existing FIB-4 criteria.

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张雪丹,姚燕峰,舒鹏.肝星状细胞分泌因子在乙型肝炎相关肝纤维化/肝硬化诊断中的价值[J].临床检验杂志,2026,44(04):248-254

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  • 收稿日期:2025-06-30
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  • 在线发布日期: 2026-06-10
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