Hypoxia-Inducible Factor-1α (HIF-1α) as a Factor to Predict the Prognosis of Spinal Chordoma

Study Design.Retrospective study.Objective.In this study, the authors explore the potential relationship between hypoxia inducible factor-1 alpha (HIF-1 alpha) and the prognosis of patients with spinal chordoma.Summary of Background Data.Currently, prognostic factors related to the clinical course in the setting of spinal chordoma are poorly understood. Although the close relationship between HIF-1 alpha and tumor angiogenesis, metastasis, and recurrence have been widely reported, it has not been investigated in the context of spinal chordoma.Materials and Methods.In this study, 32 samples of chordoma patients were compared with 14 nucleus pulposus tissues as controls. The specific expression of HIF-1 alpha was detected by immunohistochemistry. Continuous disease-free survival (CDFS) was defined as the interval from tumor resection to confirmation of the first local recurrence or distant metastasis. Overall survival (OS) was defined as the interval from the date of surgery to death related to any cause. The relationship between HIF-1 alpha expression and the clinicopathologic characteristics of patients with chordoma was analyzed using the Pearson chi 2 test. Multivariate Cox analysis was used to evaluate whether HIF-1 alpha expression was associated with the prognosis of patients after controlling for confounders.Results.HIF-1 alpha was mainly expressed in the cytoplasm or nucleus in all of the chordoma samples, which showed significantly higher than that in the normal nucleus pulposus tissue (P=0.004). Multivariate Cox regression analyses showed that high HIF-1 alpha expression and location of HIF-1 alpha expression were significantly associated with poor CDFS (hazard ratio (HR)=3.374; P=0.021) and OS (HR=4.511; P=0.012). In addition, we further found that high HIF-1 alpha expression both in the cytoplasm and nucleus indicated a stronger prognostic factor for poor CDFS (HR=3.885; P=0.011) and OS (HR=4.014; P=0.011) in spinal chordoma patients.Conclusion:High HIF-1 alpha expression may become a potential new biological indicator to predict a poor prognosis in patients with spinal chordoma. HIF-1 alpha may also represent a novel therapeutic target for the treatment of spinal chordoma.