Expression of HIF-1alpha and VEGF in colorectal cancer: association with clinical outcomes and prognostic implications

Abstract

BackgroundHypoxia-inducible factor 1 alpha (HIF-1α) and vascular endothelial growth factor (VEGF) are frequently overexpressed in numerous types of cancers and are known to be important regulators of angiogenesis. Until now, few studies have been carried out to investigate the prognostic role of these factors in solid tumors, especially in colorectal cancer (CRC). The purpose of this study was to evaluate the expression of HIF-1α and VEGF in CRC tissues, and to analyze the association of these two factors with several clinical and pathological characteristics, and patients' survival.MethodsParaffin-embedded tissue samples were retrospectively collected from 71 CRC patients, who received surgical resection between 2001 and 2002, with a median follow-up of 5 years. We examined the patterns of expression of HIF-1α and VEGF by immunohistochemistry method. Statistical analysis was performed with univariate tests and multivariate Cox proportional hazards model to evaluate the differences.ResultsExpression of HIF-1α and VEGF was positively observed in 54.93% and 56.34% among the patients, respectively. HIF-1α and VEGF status were significantly associated with tumor stage, lymph nodes and liver metastases (P < 0.05). Expression of both HIF-1α and VEGF remained significantly associated with overall survival (OS) (P < 0.01), and HIF-1α was positively correlative to VEGF in CRC (r = 0.72, P < 0.001).ConclusionsHIF-1α and VEGF could be used as biomarkers indicating tumors in advanced stage and independently implied poor prognosis in patients with CRC. Treatment that inhibits HIF-1α might be a promising targeted approach in CRC to exhibit its potential to improve outcomes in future perspective, just as VEGF targeting has proved to be.

Multivariate Analysis of Molecular Indicators for Postoperative Liver Metastasis in Colorectal Cancer Cases

“…Vascular endothelial growth factor (VEGF) is a key regulator of angiogenesis and it has been extensively studied for its role in the invasion and metastasis of cancer cells (Wang et al, 2008). Previous research suggested expression of VEGF was positively observed in the CRC patients, and VEGF status was significantly associated with tumor stage, lymph nodes and liver metastases (Zafirellis et al, 2008;Cao et al, 2009). Identically, our results demonstrated VEGF was significantly higher expressed in liver metastasis than that in non metastasis colorectal cancer, with 94.1% positive in liver metastasis group and 65.2% positive in non metastasis group.…”

Predictive Significance of VEGF and HIF-1α Expression in Patients with Metastatic Colorectal Cancer Receiving Chemotherapy Combinations with Bevacizumab

“…In a study by Cao D et al (Cao D et al, 2009). the VEGF and HIF-1α expressions of patients with operated colorectal cancer were studied regarding survival according to intensity.…”

An Insight into Total Soluble Proteins across Rice (Oryza sativa L.) Germplasm Accessions

“…Wide variation of as low as 2.8% to 9.9% for protein concentration in milled rice germplasm lines of Chhattisgarh have been reported by Chandel et al, (2005). Cao et al, (2009) found a wide variation in the levels of storage protein content (7.38-15.41%) in Chinese varieties of O. sativa rice.…”

“…The earlier workers Kennedy and Burlingame (2003), Cao et al, (2009), Silveira et al, (2010 proposed a classification for the protein contents as high (≥12%), medium (11.9-9%), and low (≤8.9%). Based on the range of protein content present in our association mapping panel, classification of high (>10.5g/100g), moderate (9.01-10.5g/100g) and low levels of proteins (<9.0g/100g) is followed.…”