CAJ | 학술논문

目的探讨食管鳞癌中缺氧诱导因子(HIF-1α)和血管生成因子(VEGF)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切端正常组织HIF-1α、VEGF表达水平.对比分析HIF-1α、VEGF在食管鳞癌组织和正常切端中的表达以及HW-1α和VEGF与肿瘤侵犯深度、淋巴结转移(含淋巴侵犯)、肿瘤组织分化程度之间的关系.结果 HIF-1α mRNA在食管鳞癌组织中的相对表达量为5.88+1.12,在食管切端正常组织中的相对表达量为4.76±1.26,前者明显高于后者(P=0.014);VEGF mRNA在食管鳞癌组织中相对表达量为12.79±2.51,在食管切端正常组织中的相对表达量为10.92±2.23,前者明显高于后者(P=0.010);食管鳞癌组织中HIF-1α蛋白质阳性率50%(21/42),明显高于正常切端组织的14%(6/42);VEGF蛋白质阳性率76%(32/42),明显高于正常切端组织的33%(14/42).HIF-1α mRNA、VEGF mRNA表达趋向于与淋巴结转移相关(分别P=0.073、P=O.063).HIF-1α蛋白质表达在胞核和(或)胞质中,HIF-1α蛋白表达与淋巴结转移及淋巴侵犯、肿瘤组织分化相关(分别P=0.013、P=0.028).但没有发现HIF-1α mRNA与VEGF蛋白之间有显著相关性.结论肿瘤组织中HIF-1α除蛋白质水平受缺氧调节外,还可能存在转录及转录后水平调节;通过对HIF-1α与临床病理关系的研究表明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与VEGF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.
목적 탐토식관린암중결양유도인자(HIF-1α)화혈관생성인자(VEGF)적표체급기여림상병리지간적관계.방법 채용형광정량RT-PCR화면역조화분별측정식관린암조직화절단정상조직HIF-1α、VEGF표체수평.대비분석HIF-1α、VEGF재식관린암조직화정상절단중적표체이급HW-1α화VEGF여종류침범심도、림파결전이(함림파침범)、종류조직분화정도지간적관계.결과 HIF-1α mRNA재식관린암조직중적상대표체량위5.88+1.12,재식관절단정상조직중적상대표체량위4.76±1.26,전자명현고우후자(P=0.014);VEGF mRNA재식관린암조직중상대표체량위12.79±2.51,재식관절단정상조직중적상대표체량위10.92±2.23,전자명현고우후자(P=0.010);식관린암조직중HIF-1α단백질양성솔50%(21/42),명현고우정상절단조직적14%(6/42);VEGF단백질양성솔76%(32/42),명현고우정상절단조직적33%(14/42).HIF-1α mRNA、VEGF mRNA표체추향우여림파결전이상관(분별P=0.073、P=O.063).HIF-1α단백질표체재포핵화(혹)포질중,HIF-1α단백표체여림파결전이급림파침범、종류조직분화상관(분별P=0.013、P=0.028).단몰유발현HIF-1α mRNA여VEGF단백지간유현저상관성.결론 종류조직중HIF-1α제단백질수평수결양조절외,환가능존재전록급전록후수평조절;통과대HIF-1α여림상병리관계적연구표명HIF-1α역여림파결전이화종류조직분화정도밀절상관.인차,HIF-1α여VEGF유가능작위반영식관암진단급진전적생물학지표,성위항혈관생성치료적파점.
Objective To investigate the expression of hypexia-indueible factor (HIF)-lαand vessel endothelial growth factor (VEGF) and their relations with the clinicopatholngical features of esophageal squamous cancer. Methods Esophageal squamous cancer tissues and normal end squamous epithelium tissues were collected from 42 patients during operation. Real-time quantitative PCR was used to detect the mRNA expression of HIF-1α and VEGF and immunohistechemistry was used to detect the protein expression of HIF-1α and VEGE The relations between the expression of HIF-1α, VEGF and depth of tumor invasion, histological grade, lymphatic invasion, and lymph node metastasis were evaluated. Results The HIF-1α mRNA expression level was 5.88 + 1.12 in the esophageal squamous cancer tissue, higher, but not significantly, than that in normal end squamous epithelium tissue 4.76±1.26 (P= 0.014). The VEGF mRNA expression level in the esophageal squamous cancer tissue was 12.79 ±2.51, higher, but not significantly, than that in the normal end squamous epithelium tissue (10.92 ±2.23 ,P=0.010). The HIF- 1α and VEGF protein positive rates in esophageal squamous cancer tissue were 50% (21/42)and 76% (32/ 42) respectively, significantly higher than those in the normal esophageal tissue [14% (6/42)and 33% (14/42) respectively, P=0.001, P=0.000]. The expression of HIF-1α mRNA and VEGF mRNA in the esophageal squamous cancer were correlated with lymph node metastasis (including lymphatic invasion) (P=0.063 and P=0.073 respectively). HIF-1α immunoreactivity was localized in the nucleus and/or cytoplasm of the cancer cells. The expression of HIF-1α protein was correlated with lymph node metastasis and histological grade(P= O.013 and P=0.028 respectively). No correlation was found between HIF-1α mRNA and VEGF protein. Condusion HIF-1α may be regulated at transcription and post-transcription levels in addition to protein leveL It also plays an important role in lymphatic metastasis of esophageal squamous cancer and tumor malignancy degree. So HIF-1α and VEGF may serve as perdictors of progression in esophageal squamous cell carcinoma and as potential targets for anti-angiogenesis therapy of esophageal squamous cell carcinoma.