Expression of hypoxia-inducible factor-1α in esophageal squamous cell carcinoma
Expression of hypoxia-inducible factor-1α in esophageal squamous cell carcinoma
复制标题
DOI：
10.1111/j.1349-7006.2005.00025.x
复制
发表时间：
2005-03-01
期刊：
影响因子：
5.7
通讯作者：
Maehara, T
中科院分区：
文献类型：
--
作者：
Matsuyama, T;Nakanishi, K;Maehara, T
缺氧诱导因子-1（Hypoxia-inducible factor-1，HIF-1）是一种转录因子，通过调节能量代谢和诱导血管生成在肿瘤的生长和转移中发挥重要作用。HIF-1 α（HIF-1的一个亚单位）的水平升高在各种恶性肿瘤中均有发现，但尚不清楚食管癌中是否如此。本研究旨在探讨HIF-1a在食管鳞癌中的表达及其临床意义。在215例食管癌患者中，我们检测了HIF-1 α蛋白、血管内皮生长因子（VEGF）蛋白和p53蛋白的免疫反应性。在38例患者中，我们检测了HIF-1 α信使核糖核酸（mRNA）的表达（使用半定量逆转录-聚合酶链反应[RT-PCR]）。HIF-1 α蛋白阳性表达在95%的患者中被识别，并且在肿瘤细胞的细胞核和/或细胞质中非常明显。HIF-1 α蛋白表达“高分”组患者的比例随着VEGF蛋白表达的增加而显著增加。在我们的单变量分析中，发现HIF-1 α蛋白的免疫反应性对无病生存率有显著影响，但对总生存率无影响。在RT-PCR中，HIF-1 α mRNA评分与HIF-1 α蛋白表达评分显著相关，但与任何临床病理因素或生存率均无关。HIF-1 α蛋白和mRNA的检测似乎对食管癌的进展和预后提供有限的信息。
Hypoxia-inducible factor-1 (HIF-1) is a transcription factor that plays an important role in tumor growth and metastasis by regulating energy metabolism and inducing angiogenesis. Elevated levels of HIF-1 alpha, a subunit of HIF-1, are noted in various malignant tumors, but it is unclear whether this is so in esophageal carcinoma. The purpose of this study was to evaluate the implications of HIF-1a expression in esophageal squamous cell carcinoma. in 215 patients with esophageal carcinoma, we examined immunoreactivity for HIF-1 alpha protein, vascular endothelial growth factor (VEGF) protein and p53 protein. In 38 patients, we examined the expression of HIF-1 alpha messenger ribonucleic acid (mRNA) (using the semiquantitative reverse transcriptase-polymerase chain reaction [RT-PCR]). A positive HIF-1 alpha protein expression was recognized in 95% of the patients, and was strongly apparent within both the nuclei and/or cytoplasm of tumor cells. The proportion of patients in the 'high score' group for HIF-1 alpha protein expression increased significantly with increasing VEGF protein expression. Immunoreactivity for HIF-1 alpha protein was found to have a significant effect on disease-free survival rate in our univariate analysis, but no effect on overall survival rate. In RT-PCR, HIF-1 alpha mRNA scores correlated significantly with scores for HIF-1 alpha protein expression, but not with any clinicopathologic factor or either of the survival rates. The detection of HIF-1 alpha protein and mRNA would appear to offer limited information as to progression and prognosis in esophageal carcinoma.