Department of Otolaryngology, The First Affiliated Hospital of Chongqing Medical University, No. 1 Youyi Road, Chongqing 400016, People's Republic of China.
J Cancer Res Clin Oncol. 2012 Apr;138(4):585-93. doi: 10.1007/s00432-011-1125-7. Epub 2011 Dec 31.
The Forkhead Box O3a transcription factor (FOXO3a) and hypoxia-inducible factor-1α (HIF-1α) have been reported to play important roles in the development and prognosis of human cancers. However, their exact roles are not clear. Therefore, we investigated the expression status and clinical significance of FOXO3a and HIF-1α expression in nasopharyngeal carcinoma.
The expression of FOXO3a and HIF-1α proteins was detected in nasopharyngeal carcinoma tissues and normal nasopharyngeal tissues by immunohistochemistry and western blot. Furthermore, we analyzed the association of FOXO3a and HIF-1α expression with various clinicopathologic factors including survival status of nasopharyngeal carcinoma patients.
FOXO3a was low expressed and HIF-1α was high expressed in nasopharyngeal carcinoma tissues, compared with normal nasopharyngeal tissues (both P < 0.05). The low expression of FOXO3a was significantly correlated with clinical stage (P = 0.003), T stage (P = 0.011), lymph node metastasis (P = 0.003), and distant metastasis (P = 0.030), and over expression of HIF-1α was significantly correlated with T stage (P = 0.026), lymph node metastasis (P = 0.002), and distant metastasis (P = 0.010). The Spearman analysis indicated that FOXO3a expression was inversely correlated with HIF-1α expression(rs = -0.598, P < 0.001). Overall survival curves estimated by Kaplan-Meier showed that tumor patients with low FOXO3a or high HIF-1α expression had significantly poorer prognosis compared with patients with high FOXO3a or low HIF-1α levels (P < 0.001, and P = 0.012, respectively). In addition, multivariate Cox regression analysis showed that T stage, distant metastasis, and FOXO3a were significant independent prognostic factors for overall survival (P = 0.011, P = 0.008, and P = 0.047, respectively).
Our results suggested that FOXO3a and HIF-1α may be considered to be important prognostic markers in nasopharyngeal carcinoma.
叉头框转录因子 O3a（FOXO3a）和缺氧诱导因子-1α（HIF-1α）已被报道在人类癌症的发展和预后中发挥重要作用。然而，其确切作用尚不清楚。因此，我们研究了 FOXO3a 和 HIF-1α在鼻咽癌中的表达状态和临床意义。
采用免疫组织化学和 Western blot 法检测鼻咽癌组织和正常鼻咽组织中 FOXO3a 和 HIF-1α 蛋白的表达。进一步分析了 FOXO3a 和 HIF-1α 表达与鼻咽癌患者生存状态等各种临床病理因素的相关性。
与正常鼻咽组织相比，鼻咽癌组织中 FOXO3a 表达降低，HIF-1α 表达升高（均 P < 0.05）。FOXO3a 低表达与临床分期（P = 0.003）、T 分期（P = 0.011）、淋巴结转移（P = 0.003）和远处转移（P = 0.030）显著相关，HIF-1α 过表达与 T 分期（P = 0.026）、淋巴结转移（P = 0.002）和远处转移（P = 0.010）显著相关。Spearman 分析表明，FOXO3a 表达与 HIF-1α 表达呈负相关（rs = -0.598，P < 0.001）。Kaplan-Meier 法估计的总生存曲线表明，FOXO3a 低表达或 HIF-1α 高表达的肿瘤患者的预后明显差于 FOXO3a 高表达或 HIF-1α 低水平的患者（P < 0.001 和 P = 0.012）。此外，多因素 Cox 回归分析显示，T 分期、远处转移和 FOXO3a 是总生存的独立预后因素（P = 0.011、P = 0.008 和 P = 0.047）。
我们的研究结果表明，FOXO3a 和 HIF-1α 可能被视为鼻咽癌的重要预后标志物。
