The circulating proteomic signature of alcohol-associated liver disease.
The circulating proteomic signature of alcohol-associated liver disease.
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酒精相关性肝病的循环蛋白质组特征
DOI：
10.1172/jci.insight.159775
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发表时间：
2022-07-22
期刊：
影响因子：
8
通讯作者：
Goodman, Russell P.
中科院分区：
文献类型：
--
作者：
Luther, Jay;Vannier, Augustin G. L.;Schaefer, Esperance A.;Goodman, Russell P.
尽管酒精相关性肝病(ALD)是晚期肝病的主要原因，但目前还没有有效的药物治疗方法。循环蛋白质组包括不同细胞和组织在正常生理功能或疾病背景下分泌的蛋白质，是揭示与ALD发病相关的新生物学的一个有吸引力的靶点。在这项工作中，我们使用基于适体的SomaScan蛋白质组学平台来量化具有ALD谱系的患者队列中超过1300种蛋白质的相对浓度。我们发现了一个与ALD严重程度相关的独特的循环蛋白质组特征，包括600多个在ALD分期之间显著不同的蛋白质，据我们所知，其中许多以前没有与ALD相关。值得注意的是，在酒精相关性肝炎患者中显著失调的某些蛋白质在亚临床ALD患者中也发生了较小程度的改变，可能是疾病进展的早期生物标志物。综上所述，我们的工作突出了ALD循环蛋白质组中广泛而明显的变化，识别了潜在的新生物标记物和治疗靶点，并为ALD研究人员和临床医生提供了蛋白质组学资源图谱。
Despite being a leading cause of advanced liver disease, alcohol-associated liver disease (ALD) has no effective medical therapies. The circulating proteome, which comprises proteins secreted by different cells and tissues in the context of normal physiological function or in the setting of disease and illness, represents an attractive target for uncovering novel biology related to the pathogenesis of ALD. In this work, we used the aptamer-based SomaScan proteomics platform to quantify the relative concentration of over 1300 proteins in a well-characterized cohort of patients with the spectrum of ALD. We found a distinct circulating proteomic signature that correlated with ALD severity, including over 600 proteins that differed significantly between ALD stages, many of which have not previously been associated with ALD to our knowledge. Notably, certain proteins that were markedly dysregulated in patients with alcohol-associated hepatitis were also altered, to a lesser degree, in patients with subclinical ALD and may represent early biomarkers for disease progression. Taken together, our work highlights the vast and distinct changes in the circulating proteome across the wide spectrum of ALD, identifies potentially novel biomarkers and therapeutic targets, and provides a proteomic resource atlas for ALD researchers and clinicians.
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DOI：
10.1002/hep.31995
发表时间：
2021-11
期刊：
Hepatology (Baltimore, Md.)
影响因子：
--
作者：
Kozumi K;Kodama T;Murai H;Sakane S;Govaere O;Cockell S;Motooka D;Kakita N;Yamada Y;Kondo Y;Tahata Y;Yamada R;Hikita H;Sakamori R;Kamada Y;Daly AK;Anstee QM;Tatsumi T;Morii E;Takehara T
通讯作者：
Takehara T
影响因子：
15.9
作者：
Sharma, Rohit;Reinstadler, Bryn;Mootha, Vamsi K.
通讯作者：
Mootha, Vamsi K.
影响因子：
5.3
作者：
Riihimaeki, M.;Hemminki, A.;Hemminki, K.
通讯作者：
Hemminki, K.
DOI：
10.1002/jcsm.12033
发表时间：
2015-12
期刊：
Journal of cachexia, sarcopenia and muscle
影响因子：
--
作者：
Lerner L;Hayes TG;Tao N;Krieger B;Feng B;Wu Z;Nicoletti R;Chiu MI;Gyuris J;Garcia JM
通讯作者：
Garcia JM
影响因子：
82.9
作者：
Suriben, Rowena;Chen, Michael;Allan, Bernard B.
通讯作者：
Allan, Bernard B.