Gastric cancer is one of the most common malignancies worldwide and is the fourth leading cause of cancer-related death in China. Gastric cancer has a high morbidity and mortality . In 2020, the gastric cancer morbidity ranked fifth worldwide, and there were approximately 1 million new cases; in addition, the gastric cancer mortality ranked fourth, and there were approximately 769,000 deaths . Gastric cancer affects twice as many men as women and is the most common cancer in men. In recent years, with the improvement of medical treatment and quality of life, the diagnosis rate of early gastric cancer patients in China has increased significantly, but the prognosis of patients is less than ideal[3, 4]. Studies have discovered a variety of novel molecular markers that can be used to effectively evaluate the prognosis of gastric cancer patients and contribute to the exploration of new treatment options.
Vascular endothelial growth factor (VEGF), a proangiogenic protein isolated from bovine pituitary follicular cells, was discovered in in experimental studies[5, 6]. In 1971, Judah Folkman proposed the hypothesis that tumor tissue can secrete "tumor angiogenic factors" (TAFs) to induce the formation of new blood vessels[7, 8]. Currently, angiogenesis is still an important part of tumor research. Studies have shown that most malignant tumors develop in tissues with dense blood vessels, such as the lung and liver, and highly vascularized malignant tumor tissues are more prone to lymphatic and hematogenous metastasis [9, 10]. When tumor tissue grows beyond the oxygen supply and nutrient requirements of the blood vessels in the area, the tumor tissue secretes angiogenic factors that enable the tumor to continue growing. It has been confirmed that esophageal cancer, lung cancer, breast cancer, renal cell carcinoma and colorectal cancer show abnormal expression of VEGF and other angiogenic factors [11, 12–14, 15]. In this study, the function of VEGF in gastric cancer was further explored.
Epithelial mesenchymal transition (EMT) is a cellular process in which cells lose their epithelial characteristics and acquire mesenchymal features [16, 17]. Under the action of some physiological or pathological factors, intercellular interactions are weakened, and the tight connection and adhesion characteristics of epithelial cells disappear, which enhances the infiltration and migration ability of the cells[18, 19]. EMT is regulated by multiple transcription factors, such as Snail, Twist, Slug, Zeb and Fox, which block the expression of E-cadherin and upregulate the expression of N-cadherin protein [20, 21, 22]. In this study, immunohistochemical detection of the expression of these two proteins in gastric cancer tissues was used as evidence of the occurrence of EMT in gastric cancer.
The goals of this study were to examine the expression of VEGF and markers of EMT in gastric cancer and to evaluate whether VEGF and EMT marker expression levels are correlated with each other and with clinicopathological parameters and prognosis. The aim of these goals was to reveal the role of VEGF in the occurrence and development of gastric cancer to provide new therapeutic targets for patients.