Open Access

ARTICLE

Reliability of tumor markers, chemokines, and metastasis-related molecules in serum

Faina Linkov¹, Yian Gu⁴, Alan A. Arslan^2,3,4, Mengling Liu⁴, Roy E. Shore^2,5, Lyudmila Velikokhatnaya¹, Karen L. Koenig^2,4, Paolo Toniolo³, Adele Marrangoni¹, Zoya Yurkovetsky¹, Anne Zeleniuch-Jacquotte^2,4, Anna E. Lokshin^1,6,7

1 Department of Medicine, University of Pittsburgh Cancer Institute, Division of Cancer Prevention and Population Science, University of Pittsburgh, Pittsburgh, USA
2 New York University Cancer Institute, New York University School of Medicine, New York, USA
3 Department of Obstetrics and Gynecology, New York University School of Medicine, New York, USA
4 Department of Environmental Medicine, New York University School of Medicine, New York, USA
5 Radiation Effects Research Foundation, Minami-ku Hiroshima-shi, Japan
6 Department of Pathology, University of Pittsburgh, Pittsburgh, USA
7 Department of Ob/Gyn Reproductive Sciences, University of Pittsburgh, Pittsburgh, USA

* Corresponding Author: F. Linkov,

European Cytokine Network 2009, 20(1), 21-26. https://doi.org/10.1684/ecn.2009.0146

Accepted 06 February 2009;

Abstract

There is a growing interest in the role that cancer biomarkers, metastasis-related molecules, and chemokines may play in the development and progression of various cancers. However, few studies have addressed the reliability of such biomarkers in healthy individuals over time. The objective of this study was to investigate the temporal reliability of multiple proteins in serum samples from healthy women who donated blood over successive years. Thirty five, postmenopausal women with two, repeated annual visits, and thirty, premenopausal women with three, repeated annual visits were randomly selected among eligible subjects from an existing, prospective cohort. Multiplexing Luminex xMAP^TM technology was used to measure the levels of 55 serum proteins representing cancer antigens, chemokines, angiogenic and anti-angiogenic factors, proteases, adipokines, apoptotic molecules, and other markers in these women. The biomarkers with high detection rates (> 60%) and acceptable reliability (intraclass correlation coefficient, ICCs ≥ 0.55) using xMAP^TM method were: cancer antigens: AFP, CA 15-3, CEA, CA-125, SCC, SAA; growth factors/related molecules: ErbB2, IGFBP-1; proteases and adhesion molecules: MMP-1, 8, 9, sE-selectin, human kallikreins (KLK) 8,10, ICAM-1, VCAM-1, chemokines: fractalkine, MCP-1,2, RANTES, MIP-1α, MIP-1β, Eotaxin, GRO-α, IP-10; inhibitors of angiogene-sis: angiostatin and endostatin; adipokines leptin and resistin; apoptotic factor: Fas, and other proteins mesothelin, myeloperoxidase (MPO), and PAI-1. The rest of the biomarkers under investigation either had ICCs less than 0.55 or had low levels of detection (< 60%). These included cancer antigens: CA 19-9, CA 72-4, MICA, S100, TTR, ULBP1, ULBP2, ULBP3; proteases: MMP 2, 3, 7, 12, 13; chemokines: MCP-3, MIF, MIG; adipokines: leptin and resistin; apoptotic factors: FasL, DR5, Cyfra 21-1; and inhibitors of angiogenesis and other markers: thrombospondin and heat shock protein (HSP) 27. In conclusion, 34 out of the 55 biomarkers investigated were present in detectable levels in > 60% of the samples, and with an ICC ≥0.55, indicating that a single serum measurement can be used in prospective epidemiological studies using the xMAP^TM method.

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