Elevated expression of hypoxia inducible factor-1 alpha is correlates to recurrence and poor outcome in gastric cancer

Background: Hypoxia-inducible factor-1 alpha (HIF-1α) is a transcription factor that plays a central role in biologic processes under hypoxic conditions, especially concerning tumor angiogenesis. In this study, we investigated the correlation of HIF-1α expression with clinicopathological characteristics, tumor recurrence and prognosis in gastric cancer (GC) after curative resection. Methods: The clinical data of 196 GC patents who underwent curative resection were analyzed retrospectively. The expressions of HIF-1α in recurrent GC tissues compared to non-recurrent GC tissues were examined, and the relationship between HIF-1α expression and clinicopathological characteristics was evaluated. In addition, these patients were followed up to investigate the relationship between HIF-1α expression and the survival time. Results: Immunohistochemical staining demonstrated that 114 of 196 GC samples (58.2%) were positive for HIF-1α. The positive rate of HIF-1α expression was significantly higher in recurrent GC tissue, than that in non-recurrent GC tissues (80.9%, 51.4%, respectively, P < 0.05). There was a close relationship between HIF-1α expression and TNM stage (P = 0.009), lymph node status (P = 0.004), differentiation (P = 0.042), vascular invasion (P = 0.019), T stage (P = 0.013) and VEGF expression (P = 0.030). Furthermore, patients with HIF-1α positive showed significantly higher recurrence and poorer prognosis than those with HIF-1α negative. Multivariate analysis showed that HIF-1α expression was a significant independent factor for tumor recurrence and overall survival. Conclusion: The results of the present study suggest that HIF-1α may be used as an unfavorable indicator in predicting tumor recurrence and prognosis for with GC after curative surgery. This study also suggests that HIF-1α might be a potential therapeutic target for GC.