Department of Anesthesiology, Qingdao Municipal Hospital, Qingdao University, Qingdao, 266071, China.
Department of Respiratory Medicine, Qingdao Municipal Hospital, Qingdao University, Qingdao, 266071, China.
Sci Rep. 2021 Nov 2;11(1):21446. doi: 10.1038/s41598-021-01007-w.
Urine is a promising resource for biomarker research. Therefore, the purpose of this study was to investigate potential urinary biomarkers to monitor the disease activity of ventilator-induced lung injury (VILI). In the discovery phase, a label-free data-dependent acquisition (DDA) quantitative proteomics method was used to profile the urinary proteomes of VILI rats. For further validation, the differential proteins were verified by parallel reaction monitoring (PRM)-targeted quantitative proteomics. In total, 727 high-confidence proteins were identified with at least 1 unique peptide (FDR ≤ 1%). Compared to the control group, 110 proteins (65 upregulated, 45 downregulated) were significantly changed in the VILI group (1.5-fold change, P < 0.05). The canonical pathways and protein-protein interaction analyses revealed that the differentially expressed proteins were enriched in multiple functions, including oxidative stress and inflammatory responses. Finally, thirteen proteins were identified as candidate biomarkers for VILI by PRM validation. Among these PRM-validated proteins, AMPN, MEP1B, LYSC1, DPP4 and CYC were previously reported as lung-associated disease biomarkers. SLC31, MEP1A, S15A2, NHRF1, XPP2, GGT1, HEXA, and ATPB were newly discovered in this study. Our results suggest that the urinary proteome might reflect the pathophysiological changes associated with VILI. These differential proteins are potential urinary biomarkers for the activity of VILI.
尿液是生物标志物研究的一种很有前途的资源。因此，本研究旨在探讨潜在的尿生物标志物，以监测呼吸机诱导性肺损伤（VILI）的疾病活动。在发现阶段，使用无标记的依赖于数据的采集（DDA）定量蛋白质组学方法来描绘 VILI 大鼠的尿液蛋白质组。为了进一步验证，通过平行反应监测（PRM）靶向定量蛋白质组学验证差异蛋白。总共鉴定出了 727 种具有至少 1 个独特肽的高可信度蛋白质（FDR≤1%）。与对照组相比，VILI 组中有 110 种蛋白质（65 种上调，45 种下调）明显变化（1.5 倍变化，P<0.05）。经典途径和蛋白质-蛋白质相互作用分析表明，差异表达的蛋白质富集在多个功能中，包括氧化应激和炎症反应。最后，通过 PRM 验证确定了 13 种 VILI 的候选生物标志物。在这些经 PRM 验证的蛋白质中，AMPN、MEP1B、LYSC1、DPP4 和 ATPB 之前被报道为与肺部相关疾病的生物标志物。SLC31、MEP1A、S15A2、NHRF1、XPP2、GGT1、HEXA 和 ATPB 是本研究新发现的。我们的研究结果表明，尿液蛋白质组可能反映与 VILI 相关的病理生理变化。这些差异蛋白可能是 VILI 活性的潜在尿生物标志物。
