Clinicopathologic Significance of HIF‐1α, CXCR4, and VEGF Expression in Colon Cancer

Abstract

We investigated the clinicopathologic significance of HIF-1, CXCR4, and VEGF expression using immumohistochemistry in human colon cancer. HIF-1, CXCR4, and VEGF high expression levels were correlated positively with TNM stage, lymph node involvement, and distant metastasis Furthermore, we found that combined high expression of any two of the three molecules (P = .028 for HIF-1/CXCR4, P = .007 for HIF-1/VEGF, and P = .004 for CXCR4/VEGF) had stronger correlation with lymph node metastasis than did each alone. However, a relationship with distant metastasis is seen only with the combinations CXCR4/VEGF (P = .069 for HIF-1/CXCR4, P = .062 for HIF-1/VEGF, and P = .035 for CXCR4/VEGF) as compared with those of single molecule high expression alone. Combined expression of all three molecules strongly correlates with lymph node metastasis and distant metastasis. The mRNA expression of HIF-1, CXCR4, and VEGF were quantified by real-time PCR in different colon cancer tissue samples, the experiment results shown that fresh colon tissue samples significantly overexpressed CXCR4 and VEGF mRNA compared with negative control. Therefore, the disease-free survival of all patients after curative resection can be considered in association with all three markers expression.

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

“…I n a s t u d y e v a l u a t i n g V E G F a n d H I F -1 immunohistochemically in normal colon mucosa, both parameters were negative. In the same study, the overexpression rate was found to be 65% for VEGF and 44% for HIF-1α in tissues with colon cancer (Wu et al, 2010). In this study, the rate of high VEGF expression was found to be 57% and overexpression of HIF-1α to be 55% in tissues with metastatic colorectal cancer.…”

Genetic Variations in the HIF1A Gene Modulate Response to Adjuvant Chemotherapy after Surgery in Patients with Colorectal Cancer

“…Hypoxic conditions allow HIF-1α to bind to HIF-1β and then become an active transcriptional factor, while the presence of oxygen leads to the degradation of HIF-1α. In a previous study, the immunohistochemical analysis in 68 CRC patients has shown that high expression levels of HIF-1α is positively associated with TNM stage, lymph node involvement, and distant metastasis (Wu et al, 2010). Similarly, another study has shown that HIF-1α over-expression is associated with the poor prognosis in a cohort of 731 CRC patients (Baba et al, 2010).…”

Prognosis and Clinicopathology of CXCR4 in Colorectal Cancer Patients: a Meta-analysis

“…Among the 18 articles, six of those were excluded due to laboratory studies, non-original articles (review), or studies irrelevant to the current analysis. Eventually, the remaining twelve studies were included for further analysis (Joseph et al, 2005;Alessandro et al, 2006;Fukunaga et al, 2006;N Yoshitake et al, 2008;Frank et al, 2009;Shang et al, 2010;Yugang et al, 2010;Adam et al, 2012;Crescenzo et al, 2013;Tinghua et al, 2013;Ying et al, 2014;Shinichiro et al, 2014) (Figure 1). …”