PDF(Pubmed)
Abstract：
UNASSIGNED: Histological assessment of liver biopsies is the gold standard for diagnosis of non-alcoholic steatohepatitis (NASH), the progressive form of non-alcoholic fatty liver disease (NAFLD), despite its well-established limitations. Therefore, non-invasive biomarkers that can offer an integrated view of the liver are needed to improve diagnosis and reduce sampling bias. Hepatic stellate cells (HSCs) are central in the development of hepatic fibrosis, a hallmark of NASH. Secreted HSC-specific proteins may, therefore, reflect disease state in the NASH liver and serve as non-invasive diagnostic biomarkers.
UNASSIGNED: We performed RNA-sequencing on liver biopsies from a histologically characterised cohort of obese patients (n = 30, BMI >35 kg/m2) to identify and evaluate HSC-specific genes encoding secreted proteins. Bioinformatics was used to identify potential biomarkers and their expression at single-cell resolution. We validated our findings using single-molecule fluorescence in situ hybridisation (smFISH) and ELISA to detect mRNA in liver tissue and protein levels in plasma, respectively.
UNASSIGNED: Hepatic expression of SPARC-related modular calcium-binding protein 2 (SMOC2) was increased in NASH compared to no-NAFLD (p.adj <0.001). Single-cell RNA-sequencing data indicated that SMOC2 was primarily expressed by HSCs, which was validated using smFISH. Finally, plasma SMOC2 was elevated in NASH compared to no-NAFLD (p <0.001), with a predictive accuracy of AUROC 0.88.
UNASSIGNED: Increased SMOC2 in plasma appears to reflect HSC activation, a key cellular event associated with NASH progression, and may serve as a non-invasive biomarker of NASH.
UNASSIGNED: Non-alcoholic fatty liver disease (NAFLD) and its progressive form, non-alcoholic steatohepatitis (NASH), are the most common forms of chronic liver diseases. Currently, liver biopsies are the gold standard for diagnosing NAFLD. Blood-based biomarkers to complement liver biopsies for diagnosis of NAFLD are required. We found that activated hepatic stellate cells, a cell type central to NAFLD pathogenesis, upregulate expression of the secreted protein SPARC-related modular calcium-binding protein 2 (SMOC2). SMOC2 was elevated in blood samples from patients with NASH and may hold promise as a blood-based biomarker for the diagnosis of NAFLD.
UNASSIGNED: We performed RNA-sequencing on liver biopsies from a histologically characterised cohort of obese patients (n = 30, BMI >35 kg/m2) to identify and evaluate HSC-specific genes encoding secreted proteins. Bioinformatics was used to identify potential biomarkers and their expression at single-cell resolution. We validated our findings using single-molecule fluorescence in situ hybridisation (smFISH) and ELISA to detect mRNA in liver tissue and protein levels in plasma, respectively.
UNASSIGNED: Hepatic expression of SPARC-related modular calcium-binding protein 2 (SMOC2) was increased in NASH compared to no-NAFLD (p.adj <0.001). Single-cell RNA-sequencing data indicated that SMOC2 was primarily expressed by HSCs, which was validated using smFISH. Finally, plasma SMOC2 was elevated in NASH compared to no-NAFLD (p <0.001), with a predictive accuracy of AUROC 0.88.
UNASSIGNED: Increased SMOC2 in plasma appears to reflect HSC activation, a key cellular event associated with NASH progression, and may serve as a non-invasive biomarker of NASH.
UNASSIGNED: Non-alcoholic fatty liver disease (NAFLD) and its progressive form, non-alcoholic steatohepatitis (NASH), are the most common forms of chronic liver diseases. Currently, liver biopsies are the gold standard for diagnosing NAFLD. Blood-based biomarkers to complement liver biopsies for diagnosis of NAFLD are required. We found that activated hepatic stellate cells, a cell type central to NAFLD pathogenesis, upregulate expression of the secreted protein SPARC-related modular calcium-binding protein 2 (SMOC2). SMOC2 was elevated in blood samples from patients with NASH and may hold promise as a blood-based biomarker for the diagnosis of NAFLD.
摘要：
未经证实：肝活检的组织学评估是非酒精性脂肪性肝炎（NASH）诊断的金标准，非酒精性脂肪性肝病（NAFLD）的进行性形式，尽管它有很好的局限性。因此,需要能够提供肝脏综合视图的非侵入性生物标志物,以改善诊断和减少采样偏倚.肝星状细胞（HSC）是肝纤维化发展的核心，NASH的标志。分泌的HSC特异性蛋白可能，因此,反映NASH肝脏的疾病状态，并作为非侵入性诊断生物标志物。
UNASSIGNED：我们对一组组织学特征的肥胖患者（n=30，BMI>35kg/m2）的肝活检进行了RNA测序，以鉴定和评估编码分泌蛋白的HSC特异性基因。生物信息学用于鉴定潜在的生物标志物及其在单细胞分辨率下的表达。我们使用单分子荧光原位杂交（smFISH）和ELISA来验证我们的发现，以检测肝组织中的mRNA和血浆中的蛋白质水平，分别。
UNASSIGNED：与非NAFLD相比，NASH中SPARC相关模块钙结合蛋白2（SMOC2）的肝表达增加（p。adj<0.001)。单细胞RNA测序数据表明SMOC2主要由HSC表达，这是用smFISH验证的。最后,与非NAFLD相比，NASH中血浆SMOC2升高（p<0.001），预测准确度为AUROC0.88。
未经证实：血浆中SMOC2增加似乎反映了HSC激活，与NASH进展相关的关键细胞事件，并且可以作为NASH的非侵入性生物标志物。
未经评估：非酒精性脂肪性肝病（NAFLD）及其进展形式，非酒精性脂肪性肝炎（NASH），是慢性肝病最常见的形式。目前,肝活检是诊断NAFLD的金标准.需要基于血液的生物标志物来补充肝活检以诊断NAFLD。我们发现激活的肝星状细胞，NAFLD发病机制的核心细胞类型，上调分泌蛋白SPARC相关模块钙结合蛋白2(SMOC2)的表达。SMOC2在NASH患者的血液样本中升高，并且可能有望作为诊断NAFLD的基于血液的生物标志物。
UNASSIGNED：我们对一组组织学特征的肥胖患者（n=30，BMI>35kg/m2）的肝活检进行了RNA测序，以鉴定和评估编码分泌蛋白的HSC特异性基因。生物信息学用于鉴定潜在的生物标志物及其在单细胞分辨率下的表达。我们使用单分子荧光原位杂交（smFISH）和ELISA来验证我们的发现，以检测肝组织中的mRNA和血浆中的蛋白质水平，分别。
UNASSIGNED：与非NAFLD相比，NASH中SPARC相关模块钙结合蛋白2（SMOC2）的肝表达增加（p。adj<0.001)。单细胞RNA测序数据表明SMOC2主要由HSC表达，这是用smFISH验证的。最后,与非NAFLD相比，NASH中血浆SMOC2升高（p<0.001），预测准确度为AUROC0.88。
未经证实：血浆中SMOC2增加似乎反映了HSC激活，与NASH进展相关的关键细胞事件，并且可以作为NASH的非侵入性生物标志物。
未经评估：非酒精性脂肪性肝病（NAFLD）及其进展形式，非酒精性脂肪性肝炎（NASH），是慢性肝病最常见的形式。目前,肝活检是诊断NAFLD的金标准.需要基于血液的生物标志物来补充肝活检以诊断NAFLD。我们发现激活的肝星状细胞，NAFLD发病机制的核心细胞类型，上调分泌蛋白SPARC相关模块钙结合蛋白2(SMOC2)的表达。SMOC2在NASH患者的血液样本中升高，并且可能有望作为诊断NAFLD的基于血液的生物标志物。
