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


CONCLUSIONS
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.
Svendsen
Mads N
MN
Department of Surgical Gastroenterology, Hvidovre Hospital, University of Copenhagen, Hvidovre, Denmark. madsnsvendsen@hotmail.com
Brünner
Nils
N
Christensen
Ib J
IJ
Ytting
Henriette
H
Bentsen
Camilla
C
Lomholt
Anne F
AF
Nielsen
Hans J
HJ
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000097:blood*; D016022:Case-Control Studies; D015179:Colorectal Neoplasms / Q000097:blood*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D042461:Vascular Endothelial Growth Factor A / Q000097:blood*; D040281:Vascular Endothelial Growth Factor Receptor-1 / Q000097:blood*
D014408:Biomarkers, Tumor; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D040281:Vascular Endothelial Growth Factor Receptor-1