Liver Tissue Proteins Improve the Accuracy of Plasma Proteins as Biomarkers in Diagnosing Metabolic Dysfunction-Associated Steatohepatitis.

IF 2.1 4区生物学 Q3 BIOCHEMICAL RESEARCH METHODS

PROTEOMICS – Clinical Applications Pub Date : 2024-11-01 Epub Date: 2024-07-28 DOI:10.1002/prca.202300236

Achuthan Sourianarayanane, Michelle R Salemi, Brett S Phinney, Arthur J McCullough

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引用次数: 0

Abstract

Background: Biomarkers for metabolic dysfunction-associated steatohepatitis (MASH) have been considered based on proteomic and lipidomic data from plasma and liver tissue without clinical benefits. This study evaluated proteomics-based plasma and liver tissue biomarkers collected simultaneously from patients with metabolic dysfunction-associated steatotic liver disease (MASLD).

Methods: Liver tissue and plasma samples were collected during liver biopsy to diagnose MASLD. Untargeted proteomics was performed on 64 patients.

Results: Twenty plasma proteins were up- or downregulated in patients with MASH compared with those without MASH. The potential biomarkers utilizing the best combinations of these plasma proteins had an area under the receiver operating curve (AUROC) of 0.671 for detecting those with MASH compared with those without it. However, none of the 20 plasma proteins were represented among the significantly regulated liver tissue proteins in patients with MASH. Ten of them displayed a trend and relevance in liver tissue with MASLD progression. These 10 plasma proteins had an AUROC of 0.793 for MASH identification and higher positive and negative predictive values.

Conclusion: The plasma and liver protein expressions of patients with MASH were not directly comparable. Plasma protein biomarkers that are also expressed in liver tissue can help improve MASH detection.

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肝组织蛋白提高了血浆蛋白作为生物标记物诊断代谢功能障碍相关性脂肪性肝炎的准确性

背景：代谢功能障碍相关性脂肪性肝炎（MASH）的生物标志物一直是根据血浆和肝组织的蛋白质组和脂质组数据考虑的，但没有临床效益。本研究评估了同时从代谢功能障碍相关性脂肪性肝病（MASLD）患者身上采集的基于蛋白质组学的血浆和肝组织生物标记物：方法：在肝脏活检过程中收集肝组织和血浆样本，以诊断MASLD。对64名患者进行了非靶向蛋白质组学研究：结果：与非 MASH 患者相比，MASH 患者有 20 种血浆蛋白被上调或下调。利用这些血浆蛋白最佳组合的潜在生物标志物的接收操作曲线下面积（AUROC）为 0.671，可检测出 MASH 患者与非 MASH 患者。然而，在 20 种血浆蛋白中，没有一种蛋白在 MASH 患者的肝组织蛋白中具有显著调节作用。其中有 10 种蛋白在 MASLD 进展的肝组织中显示出趋势和相关性。这10种血浆蛋白在MASH鉴定中的AUROC为0.793，阳性和阴性预测值均较高：结论：MASH 患者的血浆蛋白和肝脏蛋白表达没有直接可比性。结论：MASH 患者的血浆蛋白和肝脏蛋白表达并不具有直接的可比性，在肝脏组织中也有表达的血浆蛋白生物标志物有助于提高 MASH 的检测率。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

PROTEOMICS – Clinical Applications 医学-生化研究方法

CiteScore

5.20

自引率

5.00%

发文量

审稿时长

1 months

期刊介绍： PROTEOMICS - Clinical Applications has developed into a key source of information in the field of applying proteomics to the study of human disease and translation to the clinic. With 12 issues per year, the journal will publish papers in all relevant areas including: -basic proteomic research designed to further understand the molecular mechanisms underlying dysfunction in human disease -the results of proteomic studies dedicated to the discovery and validation of diagnostic and prognostic disease biomarkers -the use of proteomics for the discovery of novel drug targets -the application of proteomics in the drug development pipeline -the use of proteomics as a component of clinical trials.