Integrated plasma proteomics and lung transcriptomics reveal novel biomarkers in idiopathic pulmonary fibrosis.
Integrated plasma proteomics and lung transcriptomics reveal novel biomarkers in idiopathic pulmonary fibrosis.
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DOI：
10.1186/s12931-021-01860-3
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发表时间：
2021-10-24
影响因子：
5.8
通讯作者：
Christie JD
中科院分区：
文献类型：
--
作者：
Sivakumar P;Ammar R;Thompson JR;Luo Y;Streltsov D;Porteous M;McCoubrey C;Cantu E 3rd;Beers MF;Jarai G;Christie JD
特发性肺纤维化(IPF)是一种致命的肺部疾病，有着巨大的未得到满足的医疗需求。IPF变革性疗法的发展具有挑战性，部分原因是缺乏强大的预测预后和治疗反应的生物标志物。重要的是，IPF的循环生物标志物是有限的，没有一种在临床上使用。我们先前通过对一组移植阶段肺纤维化患者(n = 36例)与正常健康供者(n = 19例)和急性肺损伤患者(n = 11例)的肺组织进行比较，报道了晚期肺纤维化患者肺组织的失调途径和新的疾病生物标志物。在这里，我们通过Somascan-1300 SomaLogics平台对来自这些队列的匹配血浆样本进行了蛋白质组学分析。肺转录和血浆蛋白质组特征的比较分析发现，与健康对照组相比，肺间质纤维化样本中有34个差异表达分析物(折叠变化(Fc) ≥ ± 1.5，假发现比(Fdr) ≤ 0.1)。IPF样本表现出强烈的趋化、肿瘤侵袭和肥大细胞迁移途径，并下调了细胞外基质(ECM)的降解。黏膜趋化因子(CCL25和CCL28)和Th2(CCL17和CCL22)趋化因子在IPF中显著上调，且在受试者中高度相关。肥大细胞成熟趋化因子CXCL12也在IPF血浆中上调(倍数变化1.92，FDR 0.006)，并与肺功能(预测FVC的百分比)显著相关(Pearson r = −为0.38，p = 0.022)，伴随着肥大细胞类胰蛋白酶2的增加。III型和VI型胶原降解标记物(C3M和C6M)在晚期IPF中显著下调(C3M p <； 0.001和C6M p <； 0.0001 IPF)，且与细胞外基质平衡改变一致。我们的研究确定了一组在IPF中具有临床实用价值的组织和循环生物标记物，这些标记物可以在未来更大范围的队列研究中得到验证。网上版载有补充材料，可在10.1186/s12931-021-01860-3查阅。
Idiopathic pulmonary fibrosis (IPF) is a fatal lung disease with a significant unmet medical need. Development of transformational therapies for IPF is challenging in part to due to lack of robust predictive biomarkers of prognosis and treatment response. Importantly, circulating biomarkers of IPF are limited and none are in clinical use. We previously reported dysregulated pathways and new disease biomarkers in advanced IPF through RNA sequencing of lung tissues from a cohort of transplant-stage IPF patients (n = 36) in comparison to normal healthy donors (n = 19) and patients with acute lung injury (n = 11). Here we performed proteomic profiling of matching plasma samples from these cohorts through the Somascan-1300 SomaLogics platform. Comparative analyses of lung transcriptomic and plasma proteomic signatures identified a set of 34 differentially expressed analytes (fold change (FC) ≥ ± 1.5, false discovery ratio (FDR) ≤ 0.1) in IPF samples compared to healthy controls. IPF samples showed strong enrichment of chemotaxis, tumor infiltration and mast cell migration pathways and downregulated extracellular matrix (ECM) degradation. Mucosal (CCL25 and CCL28) and Th2 (CCL17 and CCL22) chemokines were markedly upregulated in IPF and highly correlated within the subjects. The mast cell maturation chemokine, CXCL12, was also upregulated in IPF plasma (fold change 1.92, FDR 0.006) and significantly correlated (Pearson r = − 0.38, p = 0.022) to lung function (%predicted FVC), with a concomitant increase in the mast cell Tryptase, TPSB2. Markers of collagen III and VI degradation (C3M and C6M) were significantly downregulated (C3M p < 0.001 and C6M p < 0.0001 IPF vs control) and correlated, Pearson r = 0.77) in advanced IPF consistent with altered ECM homeostasis. Our study identifies a panel of tissue and circulating biomarkers with clinical utility in IPF that can be validated in future studies across larger cohorts. The online version contains supplementary material available at 10.1186/s12931-021-01860-3.
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影响因子：
6.1
作者：
Masuda, T;Tanaka, H;Nagai, H
通讯作者：
Nagai, H
影响因子：
3.7
作者：
Gold L;Ayers D;Bertino J;Bock C;Bock A;Brody EN;Carter J;Dalby AB;Eaton BE;Fitzwater T;Flather D;Forbes A;Foreman T;Fowler C;Gawande B;Goss M;Gunn M;Gupta S;Halladay D;Heil J;Heilig J;Hicke B;Husar G;Janjic N;Jarvis T;Jennings S;Katilius E;Keeney TR;Kim N;Koch TH;Kraemer S;Kroiss L;Le N;Levine D;Lindsey W;Lollo B;Mayfield W;Mehan M;Mehler R;Nelson SK;Nelson M;Nieuwlandt D;Nikrad M;Ochsner U;Ostroff RM;Otis M;Parker T;Pietrasiewicz S;Resnicow DI;Rohloff J;Sanders G;Sattin S;Schneider D;Singer B;Stanton M;Sterkel A;Stewart A;Stratford S;Vaught JD;Vrkljan M;Walker JJ;Watrobka M;Waugh S;Weiss A;Wilcox SK;Wolfson A;Wolk SK;Zhang C;Zichi D
通讯作者：
Zichi D
影响因子：
3.3
作者：
Makela, Kati;Mayranpaa, Mikko I.;Myllarniemi, Marjukka
通讯作者：
Myllarniemi, Marjukka
影响因子：
12.3
作者：
Law CW;Chen Y;Shi W;Smyth GK
通讯作者：
Smyth GK
影响因子：
3.9
作者：
Nemeth J;Schundner A;Frick M
通讯作者：
Frick M