Prognostic value of serum angiogenic activity in colorectal cancer patients

Abstract

Angiogenesis, resulting from an imbalance between angiogenic activator factors and inhibitors, is required for tumour growth and metastasis. The determination of the circulating concentration of all angiogenic factors (activators and inhibitors) is not feasible at present. We have evaluated diagnostic and prognostic values of the measurement of serum angiogenic activity in colorectal carcinoma (CRC) patients. Serum proliferative activity (PA) on human umbilical vein endothelial cells (HUVEC) in vitro, and serum vascular endothelial growth factor (VEGF) levels were determined by ELISA in 53 patients with primary CRC, 16 subjects with non-neoplastic gastrointestinal disease (SC) and 34 healthy individuals. Data were compared with clinical outcome of the patients. Although serum from CRC patients significantly increased the PA of HUVEC, compared to culture control (HUVEC in medium + 10% foetal bovine serum (FBS); P < 0.001); our results indicate that serum PA in CRC patients was similar to that of SC or healthy individuals. There was no correlation between serum PA and circulating VEGF concentrations. Surgery produced a decrease of PA at 8 hrs after tumour resection in CRC patients compared to pre-surgery values (186 +/- 47 versus 213 +/- 41, P < 0.001). However, an increase in serum VEGF values was observed after surgery (280 [176-450] versus 251 [160-357] pg/ml, P = 0.004). Patients with lower PA values after surgery showed a worse outcome that those with higher PA values. Therefore, this study does not support a diagnostic value for serum angiogenic activity measured by proliferative activity on HUVEC but suggests it could have a prognostic value in CRC patients.

1

HUVE cell proliferative activity (PA) induced by serum from colorectal cancer patients (CRC, n = 53), gastrointestinal non-malignant diseases patient (SC, n = 16) and healthy individuals (healthy, n = 34). Values represent relative percentages of proliferation compared to control serum (100%). PA in CRC and SC patients and in healthy individuals were increased compared to control values (P < 0.001).

2

Serum proliferative activity in HUVE cells at 8 hr after surgery tumour removal was lower in CRC patients who died (Dead) during the time of the study compared with patients who were living (Alive) at last follow-up evaluation.

3

Kaplan-Meier overall survival curves of 45 patients, following PA values at 8 hrs after surgery less than or equal to cut-off level (n = 23) and greater than cut-off level (n = 22). Patients with PA less than or equal to cut-off level had poor prognostic.