A pipeline that integrates the discovery and verification of plasma protein biomarkers reveals candidate markers for cardiovascular disease

被引：193

作者：

Addona, Terri A. ^{[1
]}

Shi, Xu ^{[2
]}

Keshishian, Hasmik ^{[1
]}

Mani, D. R. ^{[1
]}

Burgess, Michael ^{[1
]}

Gillette, Michael A. ^{[1
,3
]}

Clauser, Karl R. ^{[1
]}

Shen, Dongxiao ^{[2
]}

Lewis, Gregory D. ^{[2
,4
,5
]}

Farrell, Laurie A. ^{[2
]}

Fifer, Michael A. ^{[2
]}

Sabatine, Marc S. ^{[2
,5
,6
]}

Gerszten, Robert E. ^{[1
,2
,4
,5
]}

Carr, Steven A. ^{[1
]}

机构：

[1] Broad Inst MIT & Harvard, Cambridge, MA USA

[2] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA

[3] Massachusetts Gen Hosp, Div Pulm, Boston, MA 02114 USA

[4] Massachusetts Gen Hosp, Ctr Immunol & Inflammatory Dis, Boston, MA 02114 USA

[5] Harvard Univ, Sch Med, Donald W Reynolds Cardiovasc Clin Res Ctr Atheros, Boston, MA USA

[6] Brigham & Womens Hosp, Div Cardiovasc, Boston, MA 02115 USA

来源：

NATURE BIOTECHNOLOGY | 2011年 / 29卷 / 07期

基金：

美国国家卫生研究院;

关键词：

HYPERTROPHIC OBSTRUCTIVE CARDIOMYOPATHY; ACUTE CORONARY SYNDROMES; MASS-SPECTROMETRY; CLINICAL UTILITY; HIGH-CONFIDENCE; REDUCTION; ASSAYS; VALIDATION; PROTEOMICS; SERUM;

D O I：

10.1038/nbt.1899

中图分类号：

Q81 [生物工程学（生物技术）]; Q93 [微生物学];

学科分类号：

071005 ; 0836 ; 090102 ; 100705 ;

摘要：

We developed a pipeline to integrate the proteomic technologies used from the discovery to the verification stages of plasma biomarker identification and applied it to identify early biomarkers of cardiac injury from the blood of patients undergoing a therapeutic, planned myocardial infarction (PMI) for treatment of hypertrophic cardiomyopathy. Sampling of blood directly from patient hearts before, during and after controlled myocardial injury ensured enrichment for candidate biomarkers and allowed patients to serve as their own biological controls. LC-MS/MS analyses detected 121 highly differentially expressed proteins, including previously credentialed markers of cardiovascular disease and > 100 novel candidate biomarkers for myocardial infarction (MI). Accurate inclusion mass screening (AIMS) qualified a subset of the candidates based on highly specific, targeted detection in peripheral plasma, including some markers unlikely to have been identified without this step. Analyses of peripheral plasma from controls and patients with PMI or spontaneous MI by quantitative multiple reaction monitoring mass spectrometry or immunoassays suggest that the candidate biomarkers may be specific to MI. This study demonstrates that modern proteomic technologies, when coherently integrated, can yield novel cardiovascular biomarkers meriting further evaluation in large, heterogeneous cohorts.

引用

页码：635 / U119

页数：11

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