Overexpression of hypoxia-inducible factor-1 alpha in gastric adenocarcinoma

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Abstract
The transcriptional factor hypoxia-inducible factor 1α (HIF-1α) controls angiogenesis and metabolism by upregulating hypoxia-induced genes, such as the vascular endothelial growth factor (VEGF) gene and the glucose transporter (GLUT-1) gene. In addition to its regulation by oncogenes or tumor suppressor genes such as HER2, p53, VHL, and PTEN, overexpression of HIF-1α is induced by hypoxia. Increased HIF-1α expression is associated with malignant potential, and with patient prognosis and response to chemoradiotherapy in some cancer types. We investigated the association between HIF-1α expression and clinicopathological characteristics, including the expression of VEGF and p53 proteins, in gastric cancer. Furthermore, we analyzed the impact of HIF-1α, VEGF, and p53 protein expression on resistance to chemotherapy in advanced gastric cancer. Among 146 specimens from patients with gastric adenocarcinoma, 89 (61.0%), 52 (35.6%), and 102 (69.9%) were positive for HIF-1α, p53, and VEGF expression, respectively. The increased expression of HIF-1α protein correlated significantly with the increased expression of p53 (P < 0.0001) and VEGF (P = 0.0007). However, overexpression of these proteins was not associated with prognosis or clinicopathological status, with the exception of infrequent distant metastases. Furthermore, overexpression of these proteins was not associated with chemosensitivity in these patients with gastric cancer. Our results indicate that overexpression of HIF-1α correlates significantly with p53 and VEGF protein expression in patients with gastric cancer; however, this overexpression shows no association with clinicopathological status, patient prognosis, or chemosensitivity.