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Circulating chromogranin A and its fragments as diagnostic and prognostic disease markers

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  • Published:
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Abstract

Chromogranin A (CgA), a secretory protein released in the blood by neuroendocrine cells and neurons, is the precursor of various bioactive fragments involved in the regulation of the cardiovascular system, metabolism, innate immunity, angiogenesis, and tissue repair. After the original demonstration that circulating CgA can serve as a biomarker for a wide range of neuroendocrine tumors, several studies have shown that increased levels of CgA can be present also in the blood of patients with cardiovascular, gastrointestinal, and inflammatory diseases with, in certain cases, important diagnostic and prognostic implications. Considering the high structural and functional heterogeneity of the CgA system, comprising precursor and fragments, it is not surprising that the different immunoassays used in these studies led, in some cases, to discrepant results. Here, we review these notions and we discuss the importance of measuring total-CgA, full-length CgA, specific fragments, and their relative levels for a more thorough assessment of the pathophysiological function and diagnostic/prognostic value of the CgA system.

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Abbreviations

CgA:

chromogranin A

VIF:

vasoconstrictive-inhibitory factor

ICAM-1:

intercellular adhesion molecule-1

MCP-1:

monocyte chemoattractant protein-1

HMGB-1:

high mobility group box-1

TNF:

tumor necrosis factor alpha

IFN:

interferon

VEGF:

vascular endothelial growth factor

FGF2:

fibroblast growth factor-2

BNP:

brain natriuretic peptide

PPIs:

proton pump inhibitors

ELISA:

enzyme-linked immunosorbent assay

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Acknowledgments

This work was supported by the Associazione Italiana per la Ricerca sul Cancro (AIRC, Special Program Molecular Clinical Oncology 5x1000-9965 and IG-19220) and by the “Ricerca Corrente” Funding scheme of the Ministry of Health, Italy. We thank Karen B. Helle for critical reading of the manuscript.

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Authors and Affiliations

  1. Division of Experimental Oncology, IRCCS San Raffaele Scientific Institute, Milan, Italy

    Angelo Corti

  2. Vita-Salute San Raffaele University, Milan, Italy

    Angelo Corti

  3. Department of Pharmacological and Biomolecular Sciences, University of Milan, Milan, Italy

    Fabrizio Marcucci

  4. Clinical Trials Centre, Istituti Clinici Scientifici Maugeri, IRCCS Pavia, Pavia, Italy

    Tiziana Bachetti

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  1. Angelo Corti
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  2. Fabrizio Marcucci
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  3. Tiziana Bachetti
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Correspondence to Angelo Corti.

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This article is part of the special issue on Chromaffin Cells in Pflügers Archiv—European Journal of Physiology

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Corti, A., Marcucci, F. & Bachetti, T. Circulating chromogranin A and its fragments as diagnostic and prognostic disease markers. Pflugers Arch - Eur J Physiol 470, 199–210 (2018). https://doi.org/10.1007/s00424-017-2030-y

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  • DOI: https://doi.org/10.1007/s00424-017-2030-y

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