Measurement of circulating levels of VEGF-A, -C, and -D and their receptors, VEGFR-1 and -2 in gastric adenocarcinoma.
OBJECTIVE
To analyze the serum levels and prognostic significance of vascular endothelial growth factor (VEGF) -A, -C, and -D, and their receptors, VEGFR-1 and -2 in gastric adenocarcinomas.


METHODS
The serum levels of VEGF family members were measured in 76 control subjects and 76 patients with gastric adenocarcinoma using an enzyme-linked immunosorbent assay (ELISA). These measurements were correlated with clinco-pathological features and survival rates.


RESULTS
The serum levels of VEGF-A and its receptor, VEGFR-1, were significantly higher in patients with gastric cancer than in healthy donors (t = 2.3, P = 0.02 and t = 4.2, P < 0.0001, respectively). In contrast, the serum levels of VEGF-D were significantly higher in control subjects than in patients (t = 2.9, P = 0.004). There was no significant difference in serum levels of VEGF-C and VEGFR-2 between patients and controls. VEGF-C was associated with advanced tumor stage and presence of metastasis. VEGFR-1 was associated with metastasis, advanced overall stage, tumor differentiation and survival. VEGFR-2 levels were associated with poor tumor differentiation. There was no significant prognostic value for any of the VEGF family members or their receptors except for VEGFR-1 where high levels were associated with a poor overall survival.


CONCLUSIONS
Serum VEGF levels vary significantly in the same cohort of patients with variable clinico-pathological features and prognostic values. The simultaneous measurement of VEGF receptors levels in sera may overcome the limitations of a single biomarker assay.
Al-Moundhri
Mansour-S
MS
Medical Oncology Unit, Department of Medicine, College of Medicine and Health Sciences, Sultan Qaboos University, Muscat, Oman. mansours@squ.edu.om
Al-Shukaili
A
A
Al-Nabhani
M
M
Al-Bahrani
B
B
Burney
I-A
IA
Rizivi
A
A
Ganguly
S-S
SS
D000230:Adenocarcinoma / Q000378:metabolism* / Q000473:pathology; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000097:blood; D016022:Case-Control Studies; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D011237:Predictive Value of Tests; D011379:Prognosis; D013274:Stomach Neoplasms / Q000378:metabolism* / Q000473:pathology; D042461:Vascular Endothelial Growth Factor A / Q000097:blood*; D042582:Vascular Endothelial Growth Factor C / Q000097:blood*; D042643:Vascular Endothelial Growth Factor D / Q000097:blood*; D040281:Vascular Endothelial Growth Factor Receptor-1 / Q000097:blood*; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000097:blood*
D014408:Biomarkers, Tumor; D042461:Vascular Endothelial Growth Factor A; D042582:Vascular Endothelial Growth Factor C; D042643:Vascular Endothelial Growth Factor D; D040281:Vascular Endothelial Growth Factor Receptor-1; D040301:Vascular Endothelial Growth Factor Receptor-2