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

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™ 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™ 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 angiogenesis: 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™ method.

Circulating levels of chemokines in psoriasis

“…For example, Linkov et al have shown that CXCL9 (also known as monokine induced by gamma-interferon, MIG), but not CXCL10 (interferon-induced protein of 10 kDa, IP-10) had low reliability (intra-class correlation coefficient, ICC50.55) on repeated blood samples collected yearly from healthy women [23]. Serum measurements of chemokines may be easier to obtain than their expression in skin samples, especially when one intends to evaluate the effect of a given therapy, since at least two skin biopsies would have to be performed.…”

An exploratory investigation of links between changes in adipokines and quality of life in individuals undergoing weight loss interventions: Possible implications for cancer research

“…Intra- and inter-assay variability of the assays ranged from 5-6% and 13-15%, respectively. Luminex technology has been shown to be a reliable tool for measuring large number of analytes in healthy individuals (25-27). …”

Longitudinal evaluation of cancer-associated biomarkers before and after weight loss in RENEW study participants: Implications for cancer risk reduction

“…Additionally, we developed panels of markers that showed significant potential to detect early cancers [26-28]. Furthermore, Luminex technology was shown to be a reliable tool for measuring large number of analytes in healthy individuals [29-31]. Thus, we wanted to expand the knowledge we accumulated in the area of cancer biomarkers to evaluate biomarker changes in healthy individuals who are at high risk for cancer development.…”