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目的探讨缺氧诱导因子1α(HIF-1α)在非小细胞肺癌(NSCLC)中的表达及其与血管生成和细胞凋亡的关系,评估它在NSCLC发生发展过程中的作用。方法采用免疫组织化学的方法检测HIF-1α在正常肺组织、良性病变、癌前病变、原位癌、非小细胞肺癌及肺癌转移淋巴结中的表达,及血管内皮生长因子(VEGF)在NSCLC中的表达;采用TUNEL法检测部分NSCLC中细胞凋亡指数AI。结果HIF-1α在支气管黏膜非典型增生、原位癌、NSCLC及肺癌转移淋巴结中的阳性表达率相似,总阳性表达率为40.0%(68/170),其在正常及良性病变中的总阳性表达率为6.0%(4/67),两组间有显著差异(P<0.01)。HIF-1α在NSCLC中的表达与各项临床病理特征均无明显相关性,仅与患者术后生存时间明显正相关(P<0.01)。VEGF在NSCLC中的表达与HIF-1α的表达呈正相关(P<0.01),与患者预后呈负相关(P=0.027)。凋亡指数(AI)在各组织类型和各分化程度的Ⅰ期肺癌中无明显差异,但生存期≥5年的肺癌患者AI明显高于生存期<5年的患者(P=0.004)。AI与HIF-1α的表达明显正相关(P=0.004)。结论HIF-1α在非小细胞肺癌组织中的表达较正常及良性病变肺组织明显上调,其与肿瘤血管生成及细胞凋亡均密切相关,在NSCLC生长中的作用具有多向性。HIF-1α可以作为评估患者预后的重要指标。
Objective To investigate the expression of hypoxia-inducible factor-1α (HIF-1α) in non-small cell lung cancer (NSCLC) and its relationship with angiogenesis and apoptosis and to evaluate its role in the development of NSCLC. Methods Immunohistochemistry was used to detect the expression of HIF-1α in normal lung tissue, benign lesions, precancerous lesions, carcinoma in situ, non-small cell lung cancer and metastatic lymph nodes of lung cancer, and the expression of vascular endothelial growth factor (VEGF) in NSCLC The apoptosis index (AI) of NSCLC was detected by TUNEL method. Results The positive expression rates of HIF-1α in atypical hyperplasia, carcinoma in situ, NSCLC and metastatic lymph nodes of lung cancer were similar, the total positive expression rate was 40.0% (68/170), and the positive rate of HIF-1α in normal and benign lesions The expression rate was 6.0% (4/67), with significant difference between the two groups (P <0.01). There was no significant correlation between the expression of HIF-1α and clinical pathological features in NSCLC, which was only positively correlated with the postoperative survival time (P <0.01). The expression of VEGF in NSCLC was positively correlated with the expression of HIF-1α (P <0.01), but negatively correlated with the prognosis (P = 0.027). There was no significant difference in apoptosis index (AI) between stage Ⅰ lung cancer with different histological types and different degrees of differentiation. However, the AI of lung cancer with survival ≥ 5 years was significantly higher than that of patients with survival of less than 5 years (P = 0.004). AI was positively correlated with the expression of HIF-1α (P = 0.004). Conclusion The expression of HIF-1α in non-small cell lung cancer tissues is significantly up-regulated compared with that in normal and benign lesions. The expression of HIF-1α is closely related to tumor angiogenesis and apoptosis, and has a multidirectional effect on the growth of NSCLC. HIF-1α can be used as an important index to evaluate the prognosis of patients.