缺氧诱导因子在食管鳞癌中的表达研究

The significance of HIF-1α expression in esophageal squamous cell carcinoma

目的:探讨食管鳞癌中缺氧诱导因子HIF-1α的表达及其与临床病理之间的关系。方法:采用荧光定量RT-PCR和免疫组化分别测定食管鳞癌组织和正常组织HIF-1α表达水平。对比分析HIF-1α在食管鳞癌组织和正常组织中的表达以及HIF-1α与肿瘤侵犯深度、淋巴结转移、肿瘤组织分化程度之间的关系。结果:食管鳞癌组织中HIF-1α mRNA表达高于食管正常组织(P=0.014),食管鳞癌组织中HIF-1α蛋白阳性率50%,明显高于正常组织的14%。HIF-1α mRNA表达趋向于与淋巴结转移相关(P=0.073)。HIF-1α蛋白表达在胞核和(或)胞浆中,HIF-1α蛋白表达与淋巴结转移、肿瘤组织分化相关(分别P=0.013、P=0.028)。结论:肿瘤组织中HIF-1α表达高于正常食管组织,其表达除蛋白水平受缺氧调节外,还可能存在转录及转录后水平调节;HIF-1α亦与淋巴结转移和肿瘤组织分化程度密切相关。因此,HIF-1α有可能作为反映食管癌诊断及进展的生物学指标,成为抗血管生成治疗的靶点。

Objective： To investigate the expression of HIF-1α and the relation with clinicopathological features of esophageal squamous cancer. Methods： HIF-1α was examined in esophageal squamous cancer tissue and normal squamous epithelium tissue with real-time quantitive PCR for gene expression and immunohistochemistry for protein expression. The relations between the expression of HIF-1α and the depth of tumor invasion, histological grade, lymphatic invasion and lymph node metastasis were evaluated. squamous cancer tissue the expression of HIF-1α mRNA was higher than in normal squamous epithelium tissue （P=0.014）. HIF-1α protein positive rate was 50% in esophageal squamous cancer tissue, while it was14% in normal esophageal tissue. The expression of HIF-1α mRNA in esophageal squamous cancer tissue tended to correlated with lymph node metastasis （P=0.063）. HIF-1α immunoreactivity was localized in the nucleus and/or cytoplasm of cancer cells. The expression of HIF-1α protein correlated with lymph node metastasis,histological grade （P=0.013 and P=0.028,respectively）. Conclusion：HIF-1α may be regulated at transcription and post-transcription level besides protein level.It also plays important role in lymphatic metastasis of esophageal squamous cancer and tumor malignancy degree.So HIF-1α may serve as predictors of progression in esophageal squamous cell carcinoma and potential targets for anti - angiogenesis therapy of esophageal squamous cell carcinoma.