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年龄相关性肌肉减少症患者的血浆生物标志物:蛋白质组学探索与实验验证

Plasma biomarkers in patients with age-related sarcopenia: a proteomic exploration and experimental validation.

作者信息

Lin Qinqing, Li Kangyong, Li Liwei, Guan Lichang, Zeng Yingtong, Cai Dake, Zhou Jing, Xu Lishu

机构信息

Department of Geriatric Gastroenterology, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, China.

Shantou University Medical College, Shantou, Guangdong, China.

出版信息

Aging Clin Exp Res. 2024 Dec 27;37(1):13. doi: 10.1007/s40520-024-02903-7.

Abstract

BACKGROUND

Various biomarkers associated with sarcopenia have been identified. However, there is a scarcity of studies exploring and validating biomarkers in individuals with age-related sarcopenia.

AIMS

This study aimed to investigate the proteome and identify potential biomarkers for age-related sarcopenia.

METHODS

Proteomic analysis and experimental validation were conducted using plasma from hospitalized older adults. Sarcopenia diagnosis was based on the Asian Working Group for Sarcopenia 2019 criteria. Data-independent acquisition-based proteomics was performed on plasma from 60 participants, with 30 diagnosed with sarcopenia and 30 without sarcopenia. Differentially expressed proteins (DEPs) were selected and evaluated by Receiver Operating Characteristic (ROC) analysis. Biomarker candidates were further quantitatively validated by enzyme-linked immunosorbent assay (ELISA) utilizing plasma from 6 participants with sarcopenia and 6 without sarcopenia.

RESULTS

A total of 39 DEPs were identified and 12 DEPs were selected for ROC analysis. 8 DEPs were included for ELISA validation based on their predictive performance. Paraoxonase-3 (PON3) consistently showed down-regulation in the sarcopenic group across both methodologies. Insulin-like growth factor-binding protein-2 (IGFBP2) showed inconsistency in the sarcopenic group, with up-regulation observed in proteomic analysis but down-regulation in ELISA.

DISCUSSION

Decline in PON3 may result in an overload of oxidative stress in skeletal muscles and contribute to sarcopenia. Protein modifications of IGFBP2 might exhibit during sarcopenia pathogenesis.

CONCLUSIONS

Plasma proteins are implicated in sarcopenia pathogenesis. PON3 is highlighted as a potential biomarker for patients with age-related sarcopenia. Further studies are imperative to gain an in-depth understanding of PON3 and IGFBP2.

摘要

背景

已鉴定出多种与肌肉减少症相关的生物标志物。然而,探索和验证与年龄相关的肌肉减少症个体中的生物标志物的研究却很匮乏。

目的

本研究旨在调查蛋白质组并确定与年龄相关的肌肉减少症的潜在生物标志物。

方法

使用住院老年人的血浆进行蛋白质组分析和实验验证。肌肉减少症的诊断基于2019年亚洲肌肉减少症工作组标准。对60名参与者的血浆进行了基于数据非依赖采集的蛋白质组学分析,其中30名被诊断为肌肉减少症,30名未患肌肉减少症。选择差异表达蛋白(DEPs)并通过受试者工作特征(ROC)分析进行评估。利用6名患有肌肉减少症和6名未患肌肉减少症参与者的血浆,通过酶联免疫吸附测定(ELISA)对候选生物标志物进行进一步定量验证。

结果

共鉴定出39个DEPs,并选择了12个DEPs进行ROC分析。基于其预测性能,8个DEPs被纳入ELISA验证。在两种方法中,对氧磷酶-3(PON3)在肌肉减少症组中均持续显示下调。胰岛素样生长因子结合蛋白-2(IGFBP2)在肌肉减少症组中表现不一致,在蛋白质组分析中观察到上调,但在ELISA中下调。

讨论

PON3的下降可能导致骨骼肌氧化应激过载,并导致肌肉减少症。IGFBP2的蛋白质修饰可能在肌肉减少症发病机制中出现。

结论

血浆蛋白与肌肉减少症发病机制有关。PON3被强调为与年龄相关的肌肉减少症患者的潜在生物标志物。必须进一步开展研究以深入了解PON3和IGFBP2。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cf9a/11671435/bb7894f59493/40520_2024_2903_Fig1_HTML.jpg

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