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目的:探讨乏氧诱导因子-1α(hypoxia-inducible factor 1α,HIF-1α)蛋白表达在口腔鳞状细胞癌颈淋巴转移中的作用及其在判断预后方面的意义。方法:1993年6月至2010年5月在北京大学口腔医院住院并接受手术治疗的原发口腔鳞状细胞癌患者125例纳入本次研究,收集所有患者的临床病理学资料,制作组织病理切片,应用免疫组织化学方法检测HIF-1α蛋白的表达情况,根据表达情况分为高表达组和低表达组,主要评估指标为颈淋巴转移率和癌相关生存率(disease-specific survival,DSS)。颈淋巴转移率与各项临床病理学参数的关系比较采用秩和检验,组间及组内癌相关生存率的差异性比较采用Kaplan-Meier分析,并应用COX多因素生存分析对DSS的独立预测因子进行统计分析。所有统计学分析均采用SPSS 17.0软件包完成。结果:随访截止日期为2013年6月1日,生存患者的中位随访时间为73个月,有75例HIF-1α高表达,48例HIF-1α低表达,2例无法评估。秩和检验分析发现,HIF-1α高表达组淋巴转移率显著高于HIF-1α低表达组(58.7%vs.37.5%,P=0.027)。Kaplan-Meier生存分析发现,HIF-1α低表达组患者无病生存率显著高于高表达组(60.4%vs.36.0%,P=0.009),癌相关生存率显著高于高表达组(70.8%vs.46.7%,P=0.005)。多因素生存分析表明,HIF-1α表达(HR=2.164,95%CI:1.150~4.074,P=0.017)和T分期(HR=1.387,95%CI:1.066~1.804,P=0.015)均是判断口腔鳞状细胞癌患者预后的独立预测因子。结论:HIF-1α蛋白表达是预测口腔鳞状细胞癌预后的独立因子,且与颈淋巴转移显著相关,能够作为口腔鳞状细胞癌潜在的分子诊断标志物和靶向治疗靶点。
Objective: To investigate the role of hypoxia-inducible factor-1α (HIF-1α) protein in cervical lymph node metastasis of oral squamous cell carcinoma and its significance in prognosis. Methods: From June 1993 to May 2010, 125 primary oral squamous cell carcinoma patients admitted to Peking University Stomatological Hospital were enrolled in this study. The clinical and pathological data of all patients were collected and histopathological sections were made The expression of HIF-1αprotein was detected by immunohistochemistry. According to the expression, HIF-1αprotein was divided into high expression group and low expression group. The main evaluation indexes were cervical lymph node metastasis rate and cancer-related survival rate (DSS). The relationship between cervical lymph node metastasis and clinicopathological parameters was compared by rank sum test. The differences between groups and in groups of cancer-related survival rates were compared using Kaplan-Meier analysis and independent predictors of DSS using COX multivariate survival analysis Factors for statistical analysis. All statistical analyzes were done using SPSS 17.0 software package. Results: The follow-up deadline was June 1, 2013, and the median follow-up time of patients surviving was 73 months. There were 75 cases of HIF-1α overexpression and 48 cases of HIF-1α overexpression. Two cases could not be evaluated. By rank sum test, the lymph node metastasis rate in HIF-1α overexpression group was significantly higher than that in HIF-1α low-expression group (58.7% vs.37.5%, P = 0.027). Kaplan-Meier survival analysis showed that the disease-free survival rate was significantly higher in patients with low expression of HIF-1α than in those with high expression (60.4% vs.36.0%, P = 0.009). The cancer-related survival rate was significantly higher than that in high expression group (70.8% vs. 46.7%, P = 0.005). Multivariate survival analysis showed that the expression of HIF-1α (HR = 2.164,95% CI: 1.150-4.074, P = 0.017) and T stage (HR = 1.387,95% CI: 1.066-1.804, P = 0.015) Independent predictors of prognosis in patients with oral squamous cell carcinoma. CONCLUSION: HIF-1α protein is an independent factor predicting the prognosis of oral squamous cell carcinoma and is significantly correlated with cervical lymph node metastasis. It may be a potential molecular diagnostic marker and target for oral squamous cell carcinoma.