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Application of Proteomics Profiling for Biomarker Discovery in Hypertrophic Cardiomyopathy

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Abstract

High-throughput proteomics profiling has never been applied to discover biomarkers in patients with hypertrophic cardiomyopathy (HCM). The objective was to identify plasma protein biomarkers that can distinguish HCM from controls. We performed a case-control study of patients with HCM (n = 15) and controls (n = 22). We carried out plasma proteomics profiling of 1129 proteins using the SOMAscan assay. We used the sparse partial least squares discriminant analysis to identify 50 most discriminant proteins. We also determined the area under the curve (AUC) of the receiver operating characteristic curve using the Monte Carlo cross validation with balanced subsampling. The average AUC was 0.94 (95% confidence interval, 0.82–1.00) and the discriminative accuracy was 89%. In HCM, 13 out of the 50 proteins correlated with troponin I and 12 with New York Heart Association class. Proteomics profiling can be used to elucidate protein biomarkers that distinguish HCM from controls.

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Abbreviations

AUC:

Area under the curve

BNP:

Brain natriuretic peptide

FDR:

False discovery rate

HCM:

Hypertrophic cardiomyopathy

LV:

Left ventricular

MCCV:

Monte Carlo cross validation

NYHA:

New York Heart Association

sPLS-DA:

Sparse partial least squares discriminant analysis

VIP:

Variable importance in projection

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Author information

Authors and Affiliations

  1. Cardiology Division, Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA

    Yuichi J. Shimada, Pouya Mohajer & Michael A. Fifer

  2. Division of Cardiology, Department of Medicine, Columbia University Medical Center, 622 West 168th Street, PH 3-342, New York, NY, 10032, USA

    Yuichi J. Shimada, Stephanie M. Kochav, Mathew S. Maurer & Muredach P. Reilly

  3. Department of Emergency Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA

    Kohei Hasegawa

  4. Clinical Medicine Division, Korea Institute of Oriental Medicine, Daejeon, Republic of Korea

    Jeeyoun Jung

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  1. Yuichi J. Shimada
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Correspondence to Yuichi J. Shimada.

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Conflict of Interest

Dr. Fifer is a consultant to and scientific advisory board member of MyoKardia. The other authors have no conflict of interest related to this article.

Human Subjects/Informed Consent Statement

All procedures followed were in accordance with the ethical standards of the responsible committee on human experimentation (institutional and national) and with the Helsinki Declaration of 1975, as revised in 2000. Informed consent was obtained from all patients for being included in the study.

Animal Studies

No animal studies were carried out by the authors for this article.

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Associate Editor Paul J. R. Barton oversaw the review of this article

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Shimada, Y.J., Hasegawa, K., Kochav, S.M. et al. Application of Proteomics Profiling for Biomarker Discovery in Hypertrophic Cardiomyopathy. J. of Cardiovasc. Trans. Res. 12, 569–579 (2019). https://doi.org/10.1007/s12265-019-09896-z

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