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与种族背景和脓毒症生存结果相关的蛋白质组学变化。

Proteomic changes associated with racial background and sepsis survival outcomes.

作者信息

Kapp Kathryn L, Arul Albert B, Zhang Kevin C, Du Liping, Yende Sachin, Kellum John A, Angus Derek C, Peck-Palmer Octavia M, Robinson Renã A S

机构信息

Department of Chemistry, Vanderbilt University, 5423 Stevenson Center, Nashville, TN, 37235, USA.

The Vanderbilt Institute of Chemical Biology, Vanderbilt University, Nashville, TN, 32732, USA.

出版信息

Mol Omics. 2022 Dec 5;18(10):923-937. doi: 10.1039/d2mo00171c.

Abstract

Intra-abdominal infection is a common cause of sepsis, and intra-abdominal sepsis leads to ∼156 000 U.S. deaths annually. African American/Black adults have higher incidence and mortality rates from sepsis compared to Non-Hispanic White adults. A limited number of studies have traced survival outcomes to molecular changes; however, these studies primarily only included Non-Hispanic White adults. Our goal is to better understand molecular changes that may contribute to differences in sepsis survival in African American/Black and Non-Hispanic White adults with primary intra-abdominal infection. We employed discovery-based plasma proteomics of patient samples from the Protocolized Care for Early Septic Shock (ProCESS) cohort ( = 107). We identified 49 proteins involved in the acute phase response and complement system whose expression levels are associated with both survival outcome and racial background. Additionally, 82 proteins differentially-expressed in survivors were specific to African American/Black or Non-Hispanic White patients, suggesting molecular-level heterogeneity in sepsis patients in key inflammatory pathways. A smaller, robust set of 19 proteins were in common in African American/Black and Non-Hispanic White survivors and may represent potential universal molecular changes in sepsis. Overall, this study identifies molecular factors that may contribute to differences in survival outcomes in African American/Black patients that are not fully explained by socioeconomic or other non-biological factors.

摘要

腹腔内感染是脓毒症的常见病因,腹腔内脓毒症每年导致约15.6万美国人死亡。与非西班牙裔白人成年人相比,非裔美国/黑人成年人脓毒症的发病率和死亡率更高。仅有少数研究将生存结果追溯至分子变化;然而,这些研究主要仅纳入了非西班牙裔白人成年人。我们的目标是更好地了解可能导致原发性腹腔内感染的非裔美国/黑人与非西班牙裔白人成年人脓毒症生存差异的分子变化。我们采用基于发现的血浆蛋白质组学方法,对早期脓毒性休克规范化治疗(ProCESS)队列中的患者样本(n = 107)进行了研究。我们鉴定出49种参与急性期反应和补体系统的蛋白质,其表达水平与生存结果和种族背景均相关。此外,82种在幸存者中差异表达的蛋白质分别是非裔美国/黑人或非西班牙裔白人患者所特有的,这表明脓毒症患者在关键炎症途径中存在分子水平的异质性。一组规模较小但可靠的19种蛋白质在非裔美国/黑人和非西班牙裔白人幸存者中是共有的,可能代表了脓毒症中潜在的普遍分子变化。总体而言,本研究确定了一些分子因素,这些因素可能导致非裔美国/黑人患者的生存结果差异,而社会经济或其他非生物学因素并不能完全解释这些差异。

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