Association of Serum Vascular Endothelial Growth Factor (VEGF) with Colorectal Cancer: A Systemic Review and Meta-Analysis Citation (original) (raw)
Related papers
Association of serum vascular endothelial growth factor vegf with colorectal cancer a systemic
Vascular endothelial growth factor (VEGF) is one of the most important regulators in angiogenesis, affecting endothelial cell survival and function. Some studies have shown that serum VEGF is higher in CRC patients than in healthy control groups while other studies have given the opposite conclusion. Therefore, this meta-analysis is purposed to systemically review and evaluate the correlation between serum VEGF and CRC. Finally, 23 studies were included in this study. The meta-analysis demonstrated that serum VEGF in the cancer group was significantly higher than that in the control group (SMD: 1.5, 95% CI: 1.05-1.95, P<0.001). However, obvious heterogeneity existed among the studies (P<0.001, I2=96%) and subgroup analyses were performed to investigate the source of this heterogeneity. The results indicated that with respect to VEGF, the correlation was significant regarding tumor location, study region, age, and study size. The results of this meta-analysis showed that serum level of VEGF might be used as a candidate biomarker for CRC patients.
Annals of Oncology
Purpose: Despite plasma biomarkers offering a number of advantages over tissue-based markers, the relationship between serum vascular endothelial growth factor (VEGF) and VEGF receptor (VEGF-R) tumor expression in colorectal cancer (CRC) is still unclear. This study was designed to establish the relationship between the concentration of serum VEGF and tumor VEGF-R expression in patients with CRC. Methods: A prospective study of consecutive patients undergoing elective colorectal surgery during 1 year. Preoperative VEGF was determined by enzyme-linked immunosorbent assay and VEGF-R3 by immunochemistry. Results: The initial sample included 134 patients with CRC diagnosis. Results showed significant association of serum values of VEGF with VEGF-R3 expression (P < 0.001), even in the presence of confounders (sex, age, body mass index, tumor location, and surgical approach). The estimated effect size was high (η 2 = 0.35). Conclusion: Serum VEGF has a significant correlation with tumoral VEGF-R3 expression in CRC.
European Journal of Surgical Oncology (EJSO), 2001
Introduction: Neo-angiogenesis, of great importance for tumour growth and nutrition, is preferentially mediated by the cytokine vascular endothelial growth factor (VEGF), which has a direct effect on vascular endothelial cell proliferation and migration. This study was designed to clarify whether VEGF is a suitable tumour marker in sera of patients with a colorectal cancer, and whether VEGF concentrations in sera and tumour tissues are correlated with tumour extension (pTNM) and especially with tumour volume or size. Furthermore, the influence of VEGF levels on patients' prognosis was examined. Methods: VEGF serum concentrations of 122 patients with colorectal cancer and 65 controls were determined with an ELISA kit. Additionally, VEGF concentrations of tumour and normal tissue were measured in 38 patients using the same ELISA. Results: Our results demonstrate that VEGF is not a suitable diagnostic tumour marker in patients with colorectal cancer due to its low sensitivity (36%). However, a combination of the serum tumour markers CEA and VEGF can significantly increase the pre-operative diagnostic sensitivity to 62%. VEGF serum levels differed significantly between patients (mean 438 pg/ml) and controls (mean 203 pg/ml), and also between tumour and normal tissue (984 vs 89 pg/ mg protein). Serum concentration showed a significant correlation to tumour volume and size. Patients with VEGF serum levels greater than cutoff had a poorer prognosis than those less than or equal to cutoff. For this reason VEGF could be used as a predictor of patients' outcome.
Prognostic value of vascular endothelial growth factor tumor tissue content of colorectal cancer
Oncology, 2005
those who remained disease free (p ! 0.001) and was independently associated with relapse-free survival (p = 0.044). Cox's proportional hazard survival analysis demonstrated that VEGF (p = 0.035) had an independent prognostic value in respect to overall survival. Conclusions: Elevated tumor VEGF content may discriminate between early and late stages of CRC and may be used as an independent prognostic parameter in the management of these patients.
Elevated serum VEGF levels in colorectal cancer patients correlate with poor survival
European Journal of Cancer, 2001
Background. Vascular endothelial growth factor (VEGF) is an angiogenic cytokine involved in the progression of solid tumors. In this study we evaluated the clinical usefulness of preoperative serum VEGF concentrations in patients with colorectal cancer. The changes in serum VEGF levels after tumor surgery were also evaluated. Methods. Serum VEGF levels were determined by an enzyme-linked immunosorbent assay in the sera of 61 healthy control subjects and 67 patients with colorectal cancer preoperatively and 7 and 30 days after surgery. Results. Serum VEGF levels in patients with colorectal cancer (median, 492 pg/mL; interquartile range, 281 to 737 pg/mL) were higher (P < .0001) than in control subjects (median, 186 pg/mL; interquartile range, 100 to 273 pg/mL). There was a significant association between serum VEGF levels and disease stage, invasion depth of the tumor, the presence of lymph node and distant metastases, and the degree of differentiation. Curative but not palliative resection of the primary tumor resulted in a significant decrease of preoperative serum VEGF levels but normalized in only 72% of patients. Failure of a return of VEGF to normal after resection for cure was associated with an increased although not statistically significant risk of metastasis during follow-up. Univariate analysis showed a lower survival rate for patients with increased preoperative serum VEGF levels (P < .002). Multivariate regression analysis showed that the prognostic value of serum VEGF level was not independent of tumor stage. Conclusions. These findings suggest that VEGF plays an important role in tumor progression and the formation of distant metastases in colorectal cancer. It is at present unclear whether serial estimation of serum VEGF is clinically useful in the prediction of tumor relapse. (Surgery 2002;131:548-55.)
Surgery, 2002
Background. Vascular endothelial growth factor (VEGF) is an angiogenic cytokine involved in the progression of solid tumors. In this study we evaluated the clinical usefulness of preoperative serum VEGF concentrations in patients with colorectal cancer. The changes in serum VEGF levels after tumor surgery were also evaluated. Methods. Serum VEGF levels were determined by an enzyme-linked immunosorbent assay in the sera of 61 healthy control subjects and 67 patients with colorectal cancer preoperatively and 7 and 30 days after surgery. Results. Serum VEGF levels in patients with colorectal cancer (median, 492 pg/mL; interquartile range, 281 to 737 pg/mL) were higher (P < .0001) than in control subjects (median, 186 pg/mL; interquartile range, 100 to 273 pg/mL). There was a significant association between serum VEGF levels and disease stage, invasion depth of the tumor, the presence of lymph node and distant metastases, and the degree of differentiation. Curative but not palliative resection of the primary tumor resulted in a significant decrease of preoperative serum VEGF levels but normalized in only 72% of patients. Failure of a return of VEGF to normal after resection for cure was associated with an increased although not statistically significant risk of metastasis during follow-up. Univariate analysis showed a lower survival rate for patients with increased preoperative serum VEGF levels (P < .002). Multivariate regression analysis showed that the prognostic value of serum VEGF level was not independent of tumor stage. Conclusions. These findings suggest that VEGF plays an important role in tumor progression and the formation of distant metastases in colorectal cancer. It is at present unclear whether serial estimation of serum VEGF is clinically useful in the prediction of tumor relapse. (Surgery 2002;131:548-55.)
OBJECTIVE: Determine the relationship between vascular endothelial growth factor (VEGF) expression and microvascular density (MVD) in primary colorectal cancer specimens including the prognostic value by evaluating the correlation between various common reported prognostic histopathologic indictors and these two angiogenic parameters. The Inter-observer reliability on VEGF and MVD measurement was also determined. MATERIAL AND METHOD: Anti-VEGF and anti-factor CD34 monoclonal antibodies immunohistochemical staining was performed in 40 randomly selected formalin-fixed paraffin-embedded colorectal cancer specimens of non-stage-IV patients who underwent curative resection using. Immunoreactive in 25% or more carcinoma cells was categorized as positive. The intensity of VEGF expression was graded in a semiquantitative fashion, ranging from 0 to 2 Tumor MVD was determined by counting any endothelial cells stained with CD34 per two randomly selected fields at x200 magnification in each slide. The correlation between VEGF expression and MVD was evaluated. Inter-observer agreement was assessed by comparing the results of VEGF and MVD measurements made by two pathologists. RESULTS: A moderate correlation was found between the percentage of positive immunoreactive cells and the intensity of VEGF immunoreactive staining (correlation value of 0.436, p < 0.05). MVD was found having no correlation with both the percentage of positive immunoreactive cells and intensity of VEGF immunoreactive staining (the correlation value of -0.056, p = 0.732 and 0.108, p = 0.506, respectively). Neither MVD nor VEGF expression in primary colorectal cancer tissue was found having a significant correlation with any common reported prognostic histopathologic indictors. In counting CD34-stained endothelial cells, this study revealed a high intra-observer correlation coefficient of 0.886 (95% CI: 0.715-0.955) for the first pathologist and 0.913 (95% CI: 0.782-0.965) for the second. High inter-observer reliability was found in both MVD and VEGF measurement with a substantial agreement (agreement: 95%, kappa = 0.643) between the two pathologists. CONCLUSION: In primary colorectal cancer tissues, there was no significant relationship between MVD and VEGF expression. This study revealed a high intra and inter-observer reliability on VEGF and MVD measurement. Neither MVD nor VEGF expression provided predictive value of advanced or aggressiveness of disease. Further studies on larger sample size would help validate these results.
Cancer Growth and Metastasis, 2011
Background The aim of the present study was to determine whether serum vascular endothelial growth factor (VEGF) can provide prognostic information independent of carcinoembryonic antigen levels in patients undergoing curative surgery. Methods Serum samples were collected from 158 patients with colorectal cancer and from 100 controls. Serum and tissue levels of VEGF were measured by enzyme-linked immunosorbent assay. Serum VEGF levels in colorectal cancer patients were compared with those in healthy controls, and we retrospectively assessed the association between serum VEGF levels and clinicopathologic findings and survival. Results VEGF expression was significantly higher in colorectal cancer tissue compared with nontumor tissue. Mean serum VEGF levels in patients were significantly higher than those in controls, and significantly higher in patients with large tumors, lymph node involvement, and distant metastases. Conclusion Elevated serum VEGF was significantly associated with p...
Scientific Reports
Colorectal cancer (CRC) is the third leading cause of cancer-related death worldwide. We examined if tumor tissue and circulating protein levels of all vascular endothelial growth factors (VeGFs) and VeGF receptors (VEGFRs) were synchronous and different in Taiwan patients with metastatic CRC (mCRC) vs. non-mCRC. We analyzed samples from 109 patients enrolled from 2005-2017, 50 with stages I/II and 59 with stages III/IV CRC. We found that VEGF-A,-B,-C,-D, placental growth factor (PlGF), VEGFR-1, VEGFR-2, and VEGFR-3 were higher in tumor tissues than non-tumor tissues. Metastatic patients had higher levels of circulating VEGFs and soluble VEGFRs (sVEGFRs) than healthy subjects, as well as higher VEGF-A,-B,-C,-D, and PlGF proteins in both tumor tissue and serum than non-metastatic patients. Protein levels of VEGF and VEGFR were mainly associated with the patient's age, tumor site, tumor size, tumor stage, and lymph node metastasis. Patients exhibiting high levels of VEGF, VEGFR, and sVEGFR had a shorter overall survival and disease-free survival than those with low levels. We conclude that synchronous changes in VeGF and VeGFR levels in CRC tissue and serum VeGF can discriminate between metastatic and non-metastatic subjects and high levels are associated with poor survival in CRC. Colorectal cancer (CRC) is the third leading cause of cancer-related death worldwide, including in Taiwan 1-3. According to cancer statistics by the World Health Organization (WHO), about 774,000 people died from CRC in 2015 2 ; while, the WHO-standardized death rate from this disease in Taiwan was 14.9% (5,687 deaths) 3. These statistics reflect its great impacts on human health and the global mortality rate. Thus, a careful examination of the specific growth factors involved and their associations with metastasis of CRC and patient survival might help in the diagnosis, determining the prognosis, and eventually in reducing the death rate from CRC. The vascular endothelial growth factor (VEGF) family, including VEGF-A,-B,-C,-D, and placental growth factor (PlGF), has been associated with the risk of CRC 4-16. In particular, high VEGF-A expression positively correlated with stages II-IV or with reduced survival in Finish CRC patients 5 ; while, bevacizumab, a recombinant humanized monoclonal antibody against VEGF-A, improved patient survival 6. In a New Zealand study, VEGF-A and-C levels correlated with the tumor grade and tumor size of CRC, VEGF-B expression was decreased in carcinomas compared with adenomas, and levels of VEGF-D were higher in normal tissues than CRC tissues 7. In addition, VEGF-C was higher in the CRC tissues of UK patients relative to normal colon epithelium and correlated with metastasis in Portugal CRC patients 8,9 ; while, VEGF-D was an independent prognostic marker for
IP innovative publication pvt. ltd, 2019
Introduction: Colorectal cancer is the most common cancer of gastrointestinal tract. It is ranked fourth in causing cancer related deaths. Compared to western world, the incidence rates are low in India. The pathogenesis involved here is tumor induced angiogenesis which is the most important factor for tumor growth, invasion and metastasis. Vascular endothelial growth factor (VEGF) is known to play a major role in angiogenesis. Aim: Is to study the expression of VEGF in colorectal malignancies and correlate the expression with histomorphological findings. Materials and Methods: Tissue samples from 30 patients with colorectal cancer of various stages, who had undergone resection during May 2016- February 2018, were taken for the study. Out of 30 cases, 27 were of Adenocarcinoma, 2 were Neuroendocrine tumors and 1 was Rectal Gastrointestinal stromal tumor. Scoring system was applied to assess the VEGF expression. Results: Patients with stage 1, well differentiated and grade 1 tumors had predominantly score 2 of VEGF expression; patients with stage 2, grade 2 and moderately differentiated tumors with mucinous component had predominantly score 3 of VEGF expression and patients with stage 3, grade 3 and poorly differentiated tumors had predominantly score 4 of VEGF expression. Thus VEGF expression was positively correlated with tumor grade, and TNM stage (p<0.05). Conclusion: Quantification of VEGF expression in colorectal cancers may give a reliable prognostic information, which could further help in selecting patients of high risk of disease progression for adjuvant therapy.