Oral squamous cell carcinoma OSCC is the most

Oral squamous cell carcinoma (OSCC) is the most frequent malignancy of the oral cavity and late-stage OSCCs with neck metastasis often associated with poor prognosis of patients. In Taiwan, the mortality rate of head and neck cancers is in fifth place in the overall population and the fourth place in male populations in 2011.
OSCC is an aggressive epithelial neoplasm. Despite the advances in early detection and treatment of OSCC in recent years, the overall survival rate of OSCC is still not promising, probably due to the lack of a good marker for early diagnosis and prediction of the progression and prognosis of OSCC. Vascular endothelial growth factor (VEGF) can promote angiogenesis which is essential for cancer growth and metastasis. Therefore, VEGF protein or mRNA may be a good marker for prediction of cancer progression and prognosis.
VEGF can increase vascular permeability, promote endothelial cell proliferation and migration, and inhibit endothelial cell apoptosis. In humans, the gene encoding VEGF is located on the short arm of chromosome 6 (6p21.3). VEGF is a mitogen for vascular endothelial geldanamycin and helps the migration and organization of vascular endothelial cells for neovascularization and tumor micrometastasis. Overexpression of VEGF mRNA or protein has been associated with aggressive progression and poor prognosis in several human cancers, including colorectal, gastric, pancreatic, and breast carcinomas as well as melanoma.
VEGF is also found to be an important angiogenic cytokine for neovascularization in head and neck cancers. Overexpression of VEGF mRNA or protein has been reported to be significantly related to poor prognosis and shorter survival as well as positive lymph node metastasis in head and neck cancer patients. In this study, we evaluated whether the VEGF mRNA level of OSCC surgical specimens could be a crucial biomarker to predict the progression, recurrence, and prognosis of OSCCs.

Methods and materials


This study measured the VEGF mRNA level in 60 OSCC and 38 NOM samples. We found a significantly lower mean VEGF mRNA ΔCT value in OSCC samples than in NOM samples, indicating an increased VEGF mRNA expression in OSCC samples than in NOM samples. Similarly, Berse et al discovered a greater VEGF mRNA expression in renal cell carcinomas and colonic adenocarcinomas than in normal kidney and normal bowel mucosa tissues, respectively. Brown et al also reported a significantly higher VEGF mRNA expression in gastrointestinal adenocarcinoma tissues than in normal epithelium. In addition, Guidi et al demonstrated an elevated VEGF mRNA and protein expression in endometrial carcinomas than in normal endometrial tissues. The significantly higher expression of VEGF mRNA in cancerous tissues than in corresponding normal tissues suggests that VEGF mRNA level can be used as a biomarker for oral, renal cell, gastrointestinal, and endometrial cancers. Indeed, upregulation of VEGF mRNA or protein has been detected in a variety of human cancers.
VEGF can promote angiogenesis which is a pivotal factor for tumor growth and metastasis. This study demonstrated a significant association of upregulation of VEGF mRNA in OSCC specimens with larger tumor size and positive lymph node metastasis. Our previous study also found a positive correlation between higher VEGF protein expression in OSCC tissues and positive regional lymph node metastasis. A positive correlation between overexpression of VEGF protein or mRNA in cancer tissues and lymph node metastasis has also been reported in head and neck SCCs as well as oral and pharyngeal SCCs.
VEGF can promote tumor growth because it can increase neovascularization. We further explained why VEGF can augment lymph node metastasis as follows. Firstly, VEGF is a mitogen for vascular endothelial cells and helps the migration and organization of vascular endothelial cells for neovascularization and tumor micrometastasis. VEGF-A and -B are mainly angiogenic factors while VEGF-C is a lymphangiogenic factor. VEGF can inhibit endothelial cell apoptosis, increase endothelial cell proliferation and migration, enhance vascular permeability, and thus promote metastasis. Secondly, VEGF augments the expression of matrix metalloproteinase 9 (MMP9) which facilitates the cancer cell invasion and metastasis. Additionally, VEGF-induced Akt phosphorylation leads to the increased motility of human OSCC cell line. Thirdly, VEGF also mediates tumor evasion of normal immune surveillance by inhibiting the development of dendritic cells, and in turn suppresses the antigen recognition and antitumor immune defense. Therefore, VEGF may promote lymph node metastases through multiple mechanisms such as an increase in tumor angiogenesis and lymphangiogenesis, an increase in tumor cell survival, motility, migration and invasion, an elevated expression of MMP9, and an inhibition of the immune surveillance by dendritic cells.