Clinical significance of preoperative serum vascular endothelial growth factor, interleukin-6, and C-reactive protein level in colorectal cancer

Abstract

BackgroundAngiogenesis is a multistep process in which many growth factors and cytokines have an essential role. Vascular endothelial growth factor (VEGF) is a potent angiogenic agent that acts as a specific mitogen for vascular endothelial cells through specific cell surface receptors. The interleukin-6 (IL-6) pathway is another mechanism linking angiogenesis to malignancy. C-reactive protein (CRP), a representative marker for inflammation, is known for its association with disease progression in many cancer types. The aim of this study was to determine preoperative serum levels of VEGF, IL-6, and CRP in colorectal carcinoma, and to correlate them with disease status and prognosis.MethodsA 132 of 143 patients who underwent curative resection for colorectal cancer were enrolled in this study. 11 patients with resection margin positive were excluded. Factors considered in analysis of the relationship between VEGF, IL-6, and CRP and histological findings. Patient prognosis was investigated. Serum levels of VEGF and IL-6 were assessed using Enzyme-Linked Immuno-Sorbent Assay (ELISA), and CRP was measured using immunoturbidimetry.ResultsMedian follow-up duration was 18.53 months (range 0.73-43.17 months) and median age of the patients was 62 years (range, 26-83 years). Mean and median levels of VEGF and CRP in colorectal cancer were significantly higher than in the normal control group; 608 vs. 334 pg/mL and 528 (range 122-3242) vs. 312 (range 16-1121) (p < 0.001); 1.05 mg/dL vs. 0.43 mg/dL and 0.22 (range 0.00-18.40) vs. 0.07 (range 0.02-6.94) (p = 0.002), respectively. However mean and median level of IL-6 in patients were not significantly higher than in control; 14.33 pg/mL vs. 5.65 pg/mL and 6.00 (range 1.02-139.17) vs. 5.30 (4.50-13.78) (p = 0.327). Although IL-6 and CRP levels were not correlated with other pathological findings, VEGF level was significantly correlated with tumor size (p = 0.012) and CEA (p = 0.038). When we established the cutoff value for VEGF (825 pg/mL), IL-6 (8.09 pg/mL), and CRP (0.51 mg/dL) by Receiver Operating Characteristic (ROC) curve, we noted that high VEGF levels tended to reduce overall survival (p = 0.053), but not significantly. However, IL-6 and CRP demonstrated no significance with regard to disease free survival (p = 0.531, p = 0.701, respectively) and overall survival (p = 0.563, p = 0.572, respectively). Multivariate analysis showed that VEGF (p = 0.032), CEA (p = 0.012), lymph node metastasis (p = 0.002), and TNM stage (p = 0.025) were independently associated with overall survival.ConclusionsPreoperative serum VEGF and CRP level increased in colorectal cancer patients. High VEGF level has been proposed as a poor prognostic factor for overall survival in patients with colorectal cancer.

Clinical significance of pre-operative neutrophil lymphocyte ratio and platelet lymphocyte ratio as prognostic factors for patients with colorectal cancer

“…CRP is an index of systemic inflammation and has been identified as a prognostic factor in patients with CRC and gastric cancer (24,25). However, serum CRP levels are not routinely assessed in the pre-operative assessment (12,14,18).…”

Metronidazole Decreases Viability of DLD-1 Colorectal Cancer Cell Line

“…[1][2][3] Incidence of CRC has grown rapidly since 1990, and is influenced by eating and lifestyle habits that include increased meat intake and reduced fiber intake, alcohol consumption, or smoking. 4,5 The treatment of CRC has undergone substantial improvements in the last 10 to 15 years in terms of screening, surgical management of resectable disease, and adjuvant chemotherapy. Moreover, 5-year survival for all patients has improved from only 50% to 62% during the last 25 years.…”

Preoperative Vascular Endothelial Growth Factor Levels as a Prognostic Marker for Stage II or III Colorectal Cancer Patients

“…Kwon et al reported that increased VEGF concentrations in colorectal cancer patients are an important prognostic factor when assessing life expectancy. 31 Altomare et al also suggested that patients, P = 0.003 and P = 0.005, respectively) and was the only independent prognostic factor in Stage II or Stage III patients (Stage II and Stage III, P = 0.001 and P = 0.03, respectively).…”