Vascular endothelial growth factor and soluble Tie-2 receptor in colorectal cancer: associations with disease recurrence.
OBJECTIVE
A delicate balance exists between pro-angiogenic factors and anti-angiogenic factors to regulate the process of angiogenesis. To investigate the relationship of VEGF-A with other angiogenic factors and to determine their clinical usefulness.


METHODS
Venous blood was obtained from 47 patients with CRC prior to curative resections. VEGF-A, sVEGFR-1, sTie-2 receptor, and TNF-alpha levels in serum were measured concurrently with quantitative ELISA. The median follow-up term for patients without cancer death was 29 months (range 20-35).


RESULTS
Both serum TNF-alpha activity and sVEGFR-1 was detectable in 17% and 74% of CRC patients, respectively. Univariate analysis demonstrated that the disease free survival was significantly associated with the tumour location (P=0.031), T category (P=0.006), TNF-alpha activity (P=0.0008), sTie-2 receptor (P=0.012) and VEGF-A (P<0.00001). From the survival analysis, a higher serum VEGF-A and sTie-2 receptor level is associated with an earlier development of metastases. Using multivariate Cox's regression analysis, the only independent predictors of outcome were sTie-2 receptor (P=0.038) and VEGF-A (P=0.006).


CONCLUSIONS
sTie-2 receptor and VEGF-A appear to associate independently with the development of metastases, with VEGF-A being the most powerful predictor of outcome. These data also suggest that measurement of pre-operative sTie-2 receptor and VEGF-A is superior to determining VEGF-A alone with regards to predictive value.
Chin
K F
KF
Medical Research Laboratory, Academic Surgical Unit, University of Hull, Wolfson Building, Hull HU6 7RX, UK.
Greenman
J
J
Reusch
P
P
Gardiner
E
E
Marme
D
D
Monson
J R T
JR
D000368:Aged; D043925:Angiogenesis Inducing Agents / Q000032:analysis; D014408:Biomarkers, Tumor / Q000032:analysis*; D015179:Colorectal Neoplasms / Q000737:chemistry* / Q000473:pathology / Q000601:surgery; D018572:Disease-Free Survival; D016228:Endothelial Growth Factors / Q000032:analysis*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000032:analysis*; D009367:Neoplasm Staging; D011237:Predictive Value of Tests; D011379:Prognosis; D011518:Proto-Oncogene Proteins; D042787:Receptor, TIE-2; D012995:Solubility; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis*; D042461:Vascular Endothelial Growth Factor A; D040281:Vascular Endothelial Growth Factor Receptor-1 / Q000032:analysis*
D043925:Angiogenesis Inducing Agents; D014408:Biomarkers, Tumor; D016228:Endothelial Growth Factors; C105373:MEN1 protein, human; D009363:Neoplasm Proteins; D011518:Proto-Oncogene Proteins; D014409:Tumor Necrosis Factor-alpha; D042461:Vascular Endothelial Growth Factor A; D042787:Receptor, TIE-2; D040281:Vascular Endothelial Growth Factor Receptor-1