Hypoxia inducible factor-1α (HIF-1α) as a factor to predict prognosis of spinal chordoma

Abstract

Study Design: Retrospective study. Objective: In this study, we explore the potential relationship between HIF-1α and 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 hypoxia inducible factor1α (HIF-1α) and tumor angiogenesis, metastasis and recurrence have been widely reported, it has been not investigated in the context of spinal chordoma. Methods: In this study, 32 samples of chordoma patients were compared to 14 nucleus pulposus tissues as controls. The specific expression of HIF-1α was detected by immunohistochemistry (IHC). 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-1α expression and the clinicopathological characteristics of patients with chordoma was analyzed using Pearson’s chi-square test. Multivariate Cox analysis was used to evaluate whether HIF-1α expression was associated with the prognosis of patients after controlling for confounders. Results: HIF-1α 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-1α expression and location of HIF-1α expression were significantly associated with poor CDFS (HR=3.374; P=0.021) and OS (HR=4.511; P=0.012). In addition, we further found that high HIF-1α expression both in 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-1α expression may become a potential new biological indicator to predict poor prognosis in patients with spinal chordoma. HIF-1α may also represent a novel therapeutic target for the treatment of spinal chordoma.