Division of Thoracic Surgery, Zhongshan Hospital, Fudan University, Shanghai 200032, China.
Chin Med J (Engl). 2011 Jan;124(1):11-8.
Hypoxia-inducible factor (HIF) may play an important role in the process of tumorigenesis as well as tumor progression. The aim of this study was to compare the expression between HIF-1α and HIF-2α in tumor angiogenesis and the overall impact on patient prognosis in human non-small cell lung cancer (NSCLC).
In the current work we compared the immunohistochemical expression of HIF-1α and HIF-2α in surgical specimens of 140 patients with NSCLC in a tissue microarray study. Relationships between HIF-α expression and clinicopathological or angiogenic factors, including prognosis, were analyzed.
High HIF-1α and HIF-2α expression was noted in 49/140 (35.0%) and in 64/140 (45.7%) of the cases, respectively. There was no direct correlation between HIF-1α and HIF-2α expression. Patients with advanced stage tumors had frequent high expression of HIF-2α (P = 0.007), and we also found a significant correlation between HIF-2α and T or N stage (P = 0.030 and 0.043, respectively). HIF-1α showed a marginal association with T stage (P = 0.084), which showed a higher expression in early stage tumors. A significant correlation (P = 0.045) was noticed between HIF-1α and vascular endothelial growth factor (VEGF) expression while the expression levels of thymidine phosphorylase (TP), cyclooxygenase (COX)-2 and microvessel density (MVD) were significantly higher in high HIF-2α tumors (P = 0.020, 0.004, and 0.046, respectively). In addition, univariate analysis of overall survival demonstrated that HIF-2α expression, but not HIF-1α, was related to poor outcome (P = 0.001) and it retained significant in multivariate analysis (P = 0.036).
Taken together, we conclude that HIF-1α and HIF-2α may differentially regulate the major angiogenic factors in different stages of the tumor process in NSCLC. HIF-2α may play a dominant role in tumor angiogenesis and appears to be of obvious value as a significant prognostic factor in NSCLC.
缺氧诱导因子（HIF）可能在肿瘤发生和肿瘤进展过程中发挥重要作用。本研究旨在比较肿瘤血管生成中 HIF-1α 和 HIF-2α 的表达，并分析其对人类非小细胞肺癌（NSCLC）患者总体预后的影响。
在目前的工作中，我们通过组织微阵列研究比较了 140 例 NSCLC 手术标本中 HIF-1α 和 HIF-2α 的免疫组织化学表达。分析了 HIF-α表达与临床病理或血管生成因子（包括预后）之间的关系。
在 140 例病例中，分别有 49/140（35.0%）和 64/140（45.7%）例患者存在 HIF-1α 和 HIF-2α 的高表达。HIF-1α 和 HIF-2α 的表达之间没有直接的相关性。晚期肿瘤患者 HIF-2α 的高表达频率较高（P=0.007），我们还发现 HIF-2α 与 T 或 N 分期之间存在显著相关性（P=0.030 和 0.043）。HIF-1α 与 T 分期呈边缘相关性（P=0.084），提示其在早期肿瘤中表达较高。HIF-1α 与血管内皮生长因子（VEGF）的表达呈显著相关性（P=0.045），而高 HIF-2α 肿瘤中的胸苷磷酸化酶（TP）、环氧化酶（COX）-2 和微血管密度（MVD）表达水平显著升高（P=0.020、0.004 和 0.046）。此外，总生存的单因素分析表明，HIF-2α表达而非 HIF-1α 与不良预后相关（P=0.001），且在多因素分析中仍具有显著性（P=0.036）。
综上所述，我们认为 HIF-1α 和 HIF-2α 可能在 NSCLC 肿瘤过程的不同阶段以不同的方式调节主要的血管生成因子。HIF-2α 可能在肿瘤血管生成中起主导作用，并作为 NSCLC 的一个显著预后因素具有明显的价值。
