Expression of VEGF, EGF and HGF in early‑ and late‑stage colorectal cancer

Abstract

The heterogenous nature of colorectal cancer (CRC) highlights the need for a better understanding of the growth factors that affect tumour growth and cancer progression. The aim of the present study was to evaluate the role of epidermal growth factor (EGF), vascular endothelial growth factor (VEGF) and hepatocyte growth factor (HGF) in the early (I and II) and late (III and IV) stages of CRC. The serum levels and mRNA expression (n=30) of the aforementioned growth factors were measured and immunohistochemistry (n=20) was performed in patients with CRC. Histological examination revealed comparable distribution of early-stage [I: 8 (26.7%) and II: 7 (23.3%)] and late-stage [III: 8 (26.7%) and IV: 7 (23.3%)] CRC. The mean serum concentrations of VEGF during the early (152.9±14.5 vs. 88.39±3.99 pg/ml; P=0.001) and late (182.7±25.8 vs. 88.39±3.99 pg/ml; P=0.002) stages were significantly higher compared with those in controls. Similarly, the mean serum concentrations of EGF in the early (409.4±7.96 vs. 153.7±13.8 pg/ml; P=0.05) and HGF in the late (90.4±17.4 vs. 56.9±4.97 pg/ml; P=0.05) stages were significantly higher compared with those in controls. The serum concentrations of VEGF, EGF and HGF were comparable between the early and late stages of CRC. Compared to normal tissues, the mRNA expression of both VEGF (P<0.001) and HGF (P<0.01) was upregulated in early-stage and downregulated in late-stage CRC. The expression of EGF remained significantly elevated during both the early and late stages of CRC (P<0.01). Histopathological analyses confirmed increased expression of VEGF in cancerous tissues compared with that in normal tissues. The present study emphasized the need for monitoring the serum levels and tissue expression of growth factors to fully elucidate their role in patients with CRC.

Clostridium butyricum alleviates dextran sulfate sodium-induced experimental colitis and promotes intestinal lymphatic vessel regeneration in mice

“…However, macrophages have an important role in inflammatory-induced lymphangiogenesis. Studies have shown that the expression of VEGF-C and VEGF-D and their receptor VEGFR-3 in macrophages has a very significant correlation with the local LV density in tumors (33,34). In one study, the blockade of VEGF-C and VEGF-D signaling decreased obstruction-induced lymphangiogenesis, and the depletion of macrophages decreased lymphangiogenesis in the obstructed kidney (35).…”

Relationship between VEGF Family Members, Their Receptors and Cell Death in the Neoplastic Transformation of Colorectal Cancer

“…Moreover, data demonstrate that levels of VEGF are in correlation with tumor stage. Therefore, it suggests a possible role of VEGF in the progression of the disease [ 40 ]. The published by Martini et al [ 41 ] showed that quantitative analysis of the VEGF-121 isoform, which is mainly detected in circulating blood, might be a predictor of response to anti-angiogenetic treatment.…”

“…Similar results were obtained in most recent studies conducted by Wang et al [ 45 ]. To the contrary, Abdulla et al [ 40 ] examined the expression of VEGF in tissues of CRC patients. Interestingly, the results have shown upregulation in the early-stage and downregulation in the late-stage of CRC in VEGF expression when compared to normal adjacent tissue.…”

The emerging era of personalized medicine in advanced colorectal cancer

“…186 High VEGF expression levels correlate with tumor stage and progression, linking them to CRC cases with a poor prognosis. 189 Various studies have implied the important role for VEGF overexpression in cancer. For example, two different splicing isoforms (VEGF121 and VEGF165) have been shown to be differentially expressed in CRC.…”

“…Arguably the most influential of these are VEGFs and their receptor family (VEGF receptor, VEGFR), which play a vital part in angiogenesis, through the stimulation of endothelial cell proliferation and migration, influencing the permeability of blood vessels, and altering both the function and morphology of these 186 . High VEGF expression levels correlate with tumor stage and progression, linking them to CRC cases with a poor prognosis 189 . Various studies have implied the important role for VEGF overexpression in cancer.…”