乏氧诱导因子-1α在口腔鳞状细胞癌颈淋巴转移中的作用  

Expression of hypoxia-inducible factor 1α is associated with lymph node metastasis in oral squamous cell carcinoma

作　　者：李健男[1] 冯芝恩[2] 王琳[3] 王衣祥[3] 郭传瑸[3] LI Jian-nan;FENG Zhi-en;WANG Lin;WANG Yi-xiang;GUO Chuan-bin(Department of General Dentistry, Peking University School and Hospital of Stomatology ＆ National Engineering Labora-tory for Digital and Material Technology of Stomatology ＆ Beijing Key Laboratory of Digital Stomatology, Beijing 100081,China;Department of Oral and Maxillofacial-Head and Neck Oncology, Beijing Stomatological Hospital, Capital Medical University, Beijing 100050, China;Department of Oral and Maxillofacial Surgery, Peking University School and Hospi-tal of Stomatology, Beijing 100081, China)

机构地区：[1]北京大学口腔医学院.口腔医院综合科口腔数字化医疗技术和材料国家工程实验室口腔数字医学北京市重点实验室,北京100081 [2]首都医科大学附属北京口腔医院口腔颌面头颈肿瘤科,北京100050 [3]北京大学口腔医学院.口腔医院口腔颌面外科,北京100081

出　　处：《北京大学学报（医学版）》2018年第1期26-32,共7页Journal of Peking University:Health Sciences

基　　金：国家自然科学基金(81470707)资助~~

摘　　要：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 explore the association between hypoxia-inducible factor l α （ HIF- l α ） ex-pression and lymph node metastasis in oral squamous cell carcinoma （ OSCC ） . Methods ： Tumor speci-mens from 125 patients with histologically- proven, surgically-treated OSCC were examined by immunohis- tochemical staining for expression of HIF- lα . The patients were divided into two groups by the expression of HIF- la , high expression of HIF-la group （ H- group） and low expression of HIF-la group （ L- group） . The main assessment parameters were lymph node metastasis rate and disease-specific survival （DSS）. The lymph node metastasis rate and clinicopathologic features were compared using Mann-Whit- ney test. The Kaplan-Meier curve was generated for each group and compared using the log-rank test.Cox proportional hazard models were utilized for multivariate analyses of HIF-la expression and other baseline factors with DSS. All calculations and analyses were performed using the SPSS 17. 0 software package. Results： The protein expression levels of HIF-la were up-regulated in OSCC and two patients were unable to evaluate. There were 48 patients in L-group and 75 patients in H- group. Lymph node me-tastasis rate was 37. 5% （18/48） for L-group and 58.7 % （44/75） for H-group （P =0. 027） . Expres-sion of HIF-la was significantly correlated with lymph node metastasis. The patients of L-group had a sig-nificantly better DSS than the patients of H-group （70. 8% vs. 46.1% , P = 0 .0 0 5 ） , while the patients of L-group had a significantly better disease-free survival （ DFS ） than the patients of H-group （60.4% vs. 36. 0% y P = 0. 009） by Kaplan-Meier method. A multivariate survival analysis also showed that HIF- la expression （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） both were the independent factors associated with prognosis. Conclusion ; HIF-lα express

关 键 词：乏氧诱导因子1Α 癌 鳞状细胞 头颈部肿瘤 淋巴转移 预后 

分 类 号：R739.8[医药卫生—肿瘤]