HIF-1α和Cox-2在骨肉瘤细胞中的表达及与临床预后的相关性分析  

Expressions of HIF-1αand Cox-2 and their prognostic significance in osteosarcoma

作　　者：杜鑫辉[1] 董扬[1] 杨庆诚[1] 

机构地区：[1]上海交通大学附属第六人民医院骨科,200233

出　　处：《中国骨与关节杂志》2012年第2期156-159,共4页Chinese Journal of Bone and Joint

摘　　要：目的本实验旨在研究骨肉瘤细胞中缺氧诱导因子-1α(hypoxia inducible factor-1α,HIF-1α)和环氧化酶-2(cyclooxygenase 2,Cox-2)的表达及分析其与临床预后的相关性。方法从我院自2003年1月至2009年1月就诊的骨肉瘤患者中筛选出18例,采集临床指标包括患者性别、年龄、发病部位、Enneking分期、组织病理学分型及术后随访患者生存情况。另选8例纤维结构不良患者作为阴性对照。采用免疫组化SP法进行肿瘤组织中HIF-1α和Cox-2表达的检测。结果 HIF-1α、Cox-2的表达均定位于细胞核内,呈棕黄(褐)色颗粒,在所有骨肉瘤患者均有表达,但表达的数量及着色强度有所差异,而纤维结构不良中无表达。单因素方差分析结果表明,HIF-1α的表达程度与患者性别(F=0.535,P=0.713)、年龄(F=0.311,P=0.865)、部位(F=1.211,P=0.353)无关,与患者的肿瘤分期(F=6.205,P=0.005)、转移灶有无(F=7.583,P=0.002)及病理类型(F=9.893,P=0.001)有关;Cox-2的表达程度与患者性别(F=1.102,P=0.381)、年龄(F=1.809,P=0.192)、部位(F=0.267,P=0.848)无关,与患者的肿瘤分期(F=7.583,P=0.003)和病理类型(F=4.721,P=0.018)及转移灶的存在与否(F=6.222,P=0.007)有关。相关分析结果表明,HIF-1α、Cox-2表达的相关系数为0.902(P<0.001),有统计学意义。Log-rank单因素生存分析表明,HIF-1α表达(P=0.001)、Cox-2表达(P=0.006)、肿瘤分期(P=0.041)、病理学分类(P=0.025)及转移灶的存在与否(P=0.001)和骨肉瘤患者预后相关,而性别(P=0.774)、年龄(P=0.089)、发病部位(P=0.117)与患者预后无关。Cox回归模型结果提示HIF-1α、Cox-2是骨肉瘤预后相关的重要因素,且HIF-1α和Cox-2的高表达提示患者预后不良。结论 (1)HIF-1α及Cox-2在所有骨肉瘤患者均有表达,但表达的数量及着色强度有所差异。(2)HIF-1α及Cox-2在骨肉瘤中表达呈正相关。(3)HIF-1α及Cox-2在骨肉瘤中的表达与肿瘤分期,转移灶的有无及病理类型有关,且高表达与Objective To investigate the expressions of hypoxia inducible factor-1α （HIF-1α） and cyclooxygenase 2 （Cox-2） and analyze their prognostic significance in osteosarcoma. Methods 18 osteosarcoma patients were selected from the patients treated in our hospital between Janurary 2003 and Janurary 2009 together with another 8 patients of fibrous dysplasia as negative control group. Patient information was obtained including gender, age, location of the lesion, grade of Ermeking system, pathological type and time of survival received from the follow-up. Immunohistochemistry was used to evaluate the expressions of HIF-1α and Cox-2 in osteosarcoma. All the data were processed in SPSS 17.0. Results All patients of osteosarcoma expressed HIF-1α and Cox-2 in the nucleus, but the number of cells stained brown and the degree of staining varied. Negative expression of HIF-1α and Cox-2 was found in control group. One-way analysis of variance （ANOVA） revealed that the degree of the expression of HIF-1α was not related with gender （F=0.535, P=-0.713）, age （F=0.311, P=-0.865） or location of the lesion （F=1.211, P=0.353） but was related with the grade （F=6.205, P=-0.005）, presence of metastasis （F=7.583, P=0.002） and pathological type （F=9.893, P=0.001）. The degree of the expression of Cox-2 was also not related with gender （F= 1.102, P=0.381）, age （F= 1.809, P=0.192） or location of the lesion （F=0.267, P=0.848） but was related with the grade （F=7.583, P=0.003）, pathological type （F=4.721, P=-0.018） and presence of metastasis （F=6.222, P=0.007）. Correlation analysis of the expressions of HIF-1α and Cox-2 showed prominent statistical significance （r=0.902, P〈0,001）. Log-rank methods suggested that the expression of HIF-1α （P=0.001）, Cox-2 （P=0.006）, the grade （P=0.041）, pathological type （P=0.025） and presence of metastasis （P=0.001） was related with patients＇ prognosis, but gender （P=0.774）, age （P=0.089） or location of the lesion

关 键 词：骨肉瘤 临床预后 缺氧诱导因子1Α (HIF-1α) 环氧化酶-2 (Cox-2) 

分 类 号：R738.1[医药卫生—肿瘤]