Novel potential biomarkers for severe alcoholic liver disease.
Novel potential biomarkers for severe alcoholic liver disease.
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严重酒精性肝病的新型生物标志物。
DOI：
10.3389/fimmu.2022.1051353
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发表时间：
2022
影响因子：
7.3
通讯作者：
中科院分区：
文献类型：
--
作者：
酒精性肝病（ALD）是晚期肝病的主要原因;然而，早期轻微的临床症状经常导致诊断和治疗延迟。侵入性肝活检是诊断ALD的金标准，不适合重复分析。本研究旨在确定可能有助于非侵入性疾病筛查和监测的潜在血清生物标志物。进行无标记LC-MS/MS定量蛋白质组学分析以鉴定发现队列中差异表达的蛋白质，然后基于KEGG、GO和String数据库进行生物信息学分析。随后通过定量测定验证优先化的蛋白质。受试者工作特征曲线下面积（AUROC）用于评估潜在生物标志物的诊断性能。在发现队列中共鉴定了161个差异表达蛋白，其中123个上调，38个下调。对B2 M、IGFALS和IGFBP 3进行了评价，当区分重度ALD患者和健康对照时，所有患者均表现出良好的诊断性能，AUROC超过0.9。B2 M、IGFBP 3和IGFALS的AUROC值分别为0.7131、0.8877和0.9896，用于区分重度ALD和非重度ALD以指示疾病严重程度。B2 M可以区分非重度ALD患者和HC参与者，AUROC值为0.8985。这些生物标志物的多种组合的效率上级优于用于监测疾病进展的现有肝纤维化评估指标，AUROC值超过0.9。IGFALS与ALT/AST呈正相关（r=0.4648，P=0.0009），可作为治疗靶点。这项蛋白质组学研究确定了三个新的候选蛋白作为有前途的循环生物标志物的临床诊断和疾病进展，也提供了蛋白质组图谱ALD的病理生理机制。
Alcoholic liver disease (ALD) is a leading cause of advanced liver disease; however, minor clinical symptoms in the early stage frequently result in delayed diagnosis and therapy. Invasive liver biopsy, the gold standard for diagnosing ALD, is unsuitable for repetitive analysis. This study aims to identify potential serum biomarkers that could contribute to non-invasive disease screening and monitoring. Label-free LC-MS/MS quantitative proteomics analysis was performed to identify differentially expressed proteins in the discovery cohort, followed by bioinformatics analysis based on the KEGG, GO, and String databases. Prioritized proteins were validated subsequently by quantitative assays. The area under the receiver operating characteristic curve (AUROC) was used to assess the diagnosis performance of potential biomarkers. A total of 161 differentially expressed proteins were identified in the discovery cohort, of which 123 were up-regulated and 38 were down-regulated. B2M, IGFALS, and IGFBP3 were evaluated, and all demonstrated excellent diagnosis performance with AUROCs of over 0.9 when distinguishing patients with severe ALD from healthy controls. The AUROC values of B2M, IGFBP3, and IGFALS were 0.7131, 0.8877, and 0.9896 for differentiating severe ALD from non-severe ALD to indicate disease severity. B2M could distinguish patients with non-severe ALD and HC participants with an AUROC value of 0.8985. The efficiency of multiple combinations of these biomarkers was superior to that of the existing liver fibrosis evaluation indices used to monitor disease progression, with AUROC values of over 0.9. IGFALS showed a positive correlation with ALT/AST (r=0.4648, P=0.0009) and may be developed as a therapeutic target. This proteomic study identified three novel candidate proteins as promising circulating biomarkers for clinical diagnosis and disease progression and also provided the proteomic atlas for ALD pathophysiological mechanisms.
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影响因子：
3.8
作者：
Amuzie, Chidozie J.;Pestka, James J.
通讯作者：
Pestka, James J.
影响因子：
4.1
作者：
Lizarazo D;Zabala V;Tong M;Longato L;de la Monte SM
通讯作者：
de la Monte SM
人类慢性酒精相关肝病中的胰岛素抵抗，神经酰胺的积累和内质网应激。
影响因子：
--
作者：
Longato L;Ripp K;Setshedi M;Dostalek M;Akhlaghi F;Branda M;Wands JR;de la Monte SM
通讯作者：
de la Monte SM
影响因子：
4.3
作者：
Lee, Seung Soo;Park, Seong Ho
通讯作者：
Park, Seong Ho
影响因子：
5.8
作者：
Heath, Karen E.;Argente, Jesus;Campos-Barros, Angel
通讯作者：
Campos-Barros, Angel