Peripheral blood neutrophil proteomic profiling with transcriptomic data integration reveals biomarkers for tuberculosis infection diagnosis.

IF 10.8 1区医学 Q1 MEDICINE, RESEARCH & EXPERIMENTAL

EBioMedicine Pub Date : 2025-09-27 DOI:10.1016/j.ebiom.2025.105945

Jiarong Yang, Zizheng Lv, Liguo Liu, Han Zhang, Jie Hu, Xingzhu Geng, Henan Xin, Zisen Liu, Lei Gao, Xiaobing Zhang, Yanli Xu, Rongmei Liu, Qi Jin, Jianhua Zheng

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引用次数: 0

Abstract

Background: Tuberculosis (TB) is one of the deadliest infectious diseases worldwide, causing millions of new cases and deaths annually. Rapid and accurate TB diagnostics are essential for TB control, yet current methods do not fully meet global needs. Peripheral blood neutrophils play a critical role in TB infection and represent a promising source of diagnostic markers.

Methods: We conducted a cross-sectional proteomic analysis to characterise neutrophil protein profiles in individuals with active TB (ATB), latent TB infection (LTBI), and healthy controls (HC). Stringent criteria were applied to identify differentially expressed proteins (DEPs) among these groups. Transcriptomic data were integrated to perform pathway enrichment analysis of DEPs. Three DEPs (B2M, TXN, and PRDX5) were further validated as candidate diagnostic biomarkers for Mycobacterium tuberculosis (MTB) infection using automated western blotting in a cohort of 319 individuals, including 71 ATB, 142 LTBI, and 106 HC.

Findings: Hundreds of DEPs were identified across the three groups. Integrated transcriptomic analysis revealed significant enrichment of DEPs in the NOD-like receptor signalling pathway. Receiver operating characteristic analysis of the three-protein combination (B2M, TXN, and PRDX5) yielded an area under the curve of 0.9847, with a sensitivity of 95.11% and a specificity of 96.23% for detecting MTB infection.

Interpretation: This study presents a comprehensive proteomic profile of neutrophils under different MTB infection states, and this three-protein combination may assist in the diagnosis of MTB infection.

Funding: This work was supported by the Chinese Academy of Medical Sciences (CAMS) Innovation Fund for Medical Sciences (2021-I2M-1-037) and the National Science and Technology Major Project of China (20212017ZX10201301-002-003).

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外周血中性粒细胞蛋白质组学分析与转录组学数据整合揭示结核感染诊断的生物标志物。

背景：结核病（TB）是全世界最致命的传染病之一，每年造成数百万新病例和死亡。快速和准确的结核病诊断对于结核病控制至关重要，但目前的方法不能完全满足全球需求。外周血中性粒细胞在结核感染中起关键作用，是一种很有前途的诊断标志物。方法：我们进行了横断面蛋白质组学分析，以表征活动性结核（ATB）、潜伏性结核感染（LTBI）和健康对照（HC）个体的中性粒细胞蛋白谱。采用严格的标准鉴定各组之间的差异表达蛋白（DEPs）。整合转录组学数据进行dep的通路富集分析。三种DEPs （B2M， TXN和PRDX5）作为结核分枝杆菌（MTB）感染的候选诊断生物标志物，在319个个体中进一步验证，包括71个ATB， 142个LTBI和106个HC。结果：在三组中发现了数百个dep。综合转录组学分析显示，在nod样受体信号通路中，DEPs显著富集。B2M、TXN、PRDX5三蛋白组合的受者工作特征分析曲线下面积为0.9847，检测MTB感染的敏感性为95.11%，特异性为96.23%。解释：本研究提供了MTB感染不同状态下中性粒细胞的综合蛋白质组学特征，这种三蛋白组合可能有助于MTB感染的诊断。中国医学科学院医学科学创新基金（2021-I2M-1-037）和国家科技重大专项（20212017ZX10201301-002-003）资助。

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

EBioMedicine Biochemistry, Genetics and Molecular Biology-General Biochemistry,Genetics and Molecular Biology

CiteScore

17.70

自引率

0.90%

发文量

579

审稿时长

5 weeks

期刊介绍： eBioMedicine is a comprehensive biomedical research journal that covers a wide range of studies that are relevant to human health. Our focus is on original research that explores the fundamental factors influencing human health and disease, including the discovery of new therapeutic targets and treatments, the identification of biomarkers and diagnostic tools, and the investigation and modification of disease pathways and mechanisms. We welcome studies from any biomedical discipline that contribute to our understanding of disease and aim to improve human health.