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目的缺氧是实体肿瘤在生长过程中的普遍现象,缺氧诱导因子(hypoxia-inducible factors,HIFs)是肿瘤适应缺氧的一类重要调节因子。本研究探讨缺氧诱导因子-2α(hypoxia-inducible factor-2α,HIF-2α)在非小细胞肺癌(non-small cell lung cancer,NSCLC)组织中的表达及其临床意义。方法收集2006-03-01-2010-12-20内蒙古医科大学附属医院手术切除NSCLC患者的蜡块标本112例,同时收集该院同时期20例正常肺组织蜡块标本。采用免疫组织化学方法检测112例NSCLC组织和20例正常肺组织中HIF-2α的表达,分析其与NSCLC临床病理特征和预后的关系。结果 NSCLC组织中HIF-2α阳性表达显著高于正常肺组织,在112例NSCLC标本中高表达率为47.3%(53/112)。HIF-2α高表达在高分化组的表达率为25.0%(7/28),低于中分化组的55.0%(33/60)和低分化组的54.2%(13/24),P<0.05;无淋巴结转移者HIF-2α蛋白的高表达占38.3%(23/60),显著低于有淋巴结转移者的57.7%(30/52),P<0.05;HIF-2α高表达在TNMⅠ期的表达率为28.1%(9/32),低于Ⅱ期的42.5%(17/40)和Ⅲ+Ⅳ期的67.5%(27/40),P<0.05。HIF-2α的高表达与性别、年龄、肿瘤大小及病理类型无关,P>0.05。Kaplan-Meier法生存分析显示,HIF-2α高表达是NSCLC患者预后的不良因素;TNMⅠ期患者有较好的预后。多因素回归分析显示,分化程度和TNM分期是NSCLC预后的独立因素。结论HIF-2α可能在NSCLC的发生发展及浸润转移中起重要作用,对NSCLC预后评估有一定的参考价值,肿瘤分化程度和TNM分期可作为判断NSCLC预后的指标。
Objective Hypoxia is a common phenomenon in the growth of solid tumors. Hypoxia-inducible factors (HIFs) are important regulators of tumor adaptation to hypoxia. This study was aimed to investigate the expression of hypoxia-inducible factor-2α (HIF-2α) in non-small cell lung cancer (NSCLC) and its clinical significance. Methods A total of 112 cases of paraffin - embedded specimens from patients with NSCLC underwent surgical resection in the Affiliated Hospital of Inner Mongolia Medical University from 2006-03-01-2010-12-20. Meanwhile, 20 paraffin - embedded specimens of normal lung tissue from the same period of the hospital were collected. The expression of HIF-2α in 112 NSCLC tissues and 20 normal lung tissues was detected by immunohistochemistry. The relationship between HIF-2α and the clinicopathological features and prognosis of NSCLC was analyzed. Results The positive expression of HIF-2α in NSCLC tissues was significantly higher than that in normal lung tissues. The positive rate of HIF-2α in 112 NSCLC specimens was 47.3% (53/112). The positive rate of HIF-2α expression in well-differentiated group was 25.0% (7/28), lower than 55.0% (33/60) in moderately differentiated group and 54.2% (13/24) in poorly differentiated group, P <0.05 ; High expression of HIF-2α protein in non-lymph node metastasis accounted for 38.3% (23/60), which was significantly lower than that in patients with lymph node metastasis (57.7%, P <0.05); High expression of HIF- The expression rate was 28.1% (9/32), lower than 42.5% (17/40) in stage Ⅱ and 67.5% (27/40) in stage Ⅲ + Ⅳ, P <0.05. The high expression of HIF-2α was not related to gender, age, tumor size and pathological type, P> 0.05. Survival analysis by Kaplan-Meier method showed that high expression of HIF-2α was a negative prognostic factor in patients with NSCLC. Patients with TNMⅠhave better prognosis. Multivariate regression analysis showed that the degree of differentiation and TNM staging were independent prognostic factors of NSCLC. Conclusions HIF-2α may play an important role in the occurrence, development and invasion and metastasis of NSCLC. It may be useful to evaluate the prognosis of NSCLC. The differentiation degree of tumor and TNM stage may be used as an index to judge the prognosis of NSCLC.