Biological variations in plasma VEGF and VEGFR-1 may compromise their biomarker value in colorectal cancer

TY - JOUR

T1 - Biological variations in plasma VEGF and VEGFR-1 may compromise their biomarker value in colorectal cancer

AU - Svendsen, Mads N.

AU - Brunner, Nils

AU - Christensen, Ib Jarle

AU - Ytting, Henriette

AU - Bentsen, Camilla

AU - Lomholt, Anne F.

AU - Nielsen, Hans J.

PY - 2010/11

Y1 - 2010/11

N2 - Introduction. Vascular Endothelial Growth Factor (VEGF) plays a prominent role in tumor angiogenesis and plasma VEGF concentration may carry prognostic information in colorectal cancer. The VEGF receptor 1 (VEGFR-1) is a regulatory receptor which is shredded into plasma of patients with colorectal cancer. For both molecules, large biological variation and lack of standardization of assay procedures are major challenges. Methods. We investigated pre-analytical, analytical, as well as short term and long term biological variation of plasma VEGF and VEGFR-1 in volunteers. In addition, we evaluated plasma VEGF and VEGFR-1 as markers of colorectal disease in a case-control study on four groups of 77 individuals undergoing bowel endoscopy. Groups were categorized as 'no findings', 'non-malignant findings', 'adenoma', or 'colorectal cancer'. Results. In the studies on variation, temperature and delay before centrifugation significantly influenced plasma VEGF and, to a minor extent, plasma VEGFR-1 concentrations. In addition, we found large biological variations with CV up to 69.2% for VEGF and CV up to 35.9% for VEGFR-1. For both molecules the intra-subject variation exceeded the inter-subject variation. In the case control study neither plasma VEGF nor VEGFR-1 was able to differentiate between the four groups of individuals although plasma VEGFR-1 was significantly lower in patients with 'no findings'. Conclusion. There was no difference in plasma VEGF or VEGFR-1 between patients with no findings, benign disease, pre-malignant findings, and malignant findings after endoscopy. The poor discrimination between patients may be explained by the large inter- and intra-subject variations found for both molecules in volunteers.

AB - Introduction. Vascular Endothelial Growth Factor (VEGF) plays a prominent role in tumor angiogenesis and plasma VEGF concentration may carry prognostic information in colorectal cancer. The VEGF receptor 1 (VEGFR-1) is a regulatory receptor which is shredded into plasma of patients with colorectal cancer. For both molecules, large biological variation and lack of standardization of assay procedures are major challenges. Methods. We investigated pre-analytical, analytical, as well as short term and long term biological variation of plasma VEGF and VEGFR-1 in volunteers. In addition, we evaluated plasma VEGF and VEGFR-1 as markers of colorectal disease in a case-control study on four groups of 77 individuals undergoing bowel endoscopy. Groups were categorized as 'no findings', 'non-malignant findings', 'adenoma', or 'colorectal cancer'. Results. In the studies on variation, temperature and delay before centrifugation significantly influenced plasma VEGF and, to a minor extent, plasma VEGFR-1 concentrations. In addition, we found large biological variations with CV up to 69.2% for VEGF and CV up to 35.9% for VEGFR-1. For both molecules the intra-subject variation exceeded the inter-subject variation. In the case control study neither plasma VEGF nor VEGFR-1 was able to differentiate between the four groups of individuals although plasma VEGFR-1 was significantly lower in patients with 'no findings'. Conclusion. There was no difference in plasma VEGF or VEGFR-1 between patients with no findings, benign disease, pre-malignant findings, and malignant findings after endoscopy. The poor discrimination between patients may be explained by the large inter- and intra-subject variations found for both molecules in volunteers.

KW - Former LIFE faculty

KW - Biological variation

KW - blood plasma

KW - diagnostic marker

KW - EDTA plasma

KW - biological variation

KW - vascular endothelial growth factor A

KW - vascular endothelial growth factor receptor-1

U2 - 10.3109/00365513.2010.521254

DO - 10.3109/00365513.2010.521254

M3 - Journal article

C2 - 20873967

SN - 0036-5513

VL - 70

SP - 503

EP - 511

JO - Scandinavian Journal of Clinical & Laboratory Investigation

JF - Scandinavian Journal of Clinical & Laboratory Investigation

IS - 7

ER -