Jiang Ying-An, Fan Li-Fang, Jiang Chong-Qing, Zhang You-Yuan, Luo He-Sheng, Tang Zhi-Jiao, Xia Dong, Wang Ming
Department of Gastroenterology, Renming Hospital of Wuhan University, Wuhan 435000, Hubei Province, China.
World J Gastroenterol. 2003 Mar;9(3):491-4. doi: 10.3748/wjg.v9.i3.491.
To investigate the expression and significance of PTEN, hypoxia-inducible factor-1 alpha (HIF-1alpha), and targeting gene VEGF during colorectal carciogenesis.
Total 71 cases colorectal neoplasms (9 cases of colorectal adenoma and 62 colorectal adenocarcinoma) were formalin fixed and paraffin-embedded, and all specimens were evaluated for PTEN mRNA, HIF-1alpha mRNA and VEGF protein expression. PTEN mRNA, HIF-1alpha mRNA were detected by in situ hybridization. VEGF protein was identified by citrate-microwave SP immunohistochemical method.
There were significant differences in PTEN, HIF-1alpha and VEGF expression between colorectal adenomas and colorectal adenocarcinoma (P<0.05). The level of PTEN expression decreased as the pathologic stage increased. Conversely, HIF-1alpha and VEGF expression increased with the Dukes stage as follows: stage A (0.1029+/-0.0457: 0.1207+/-0.0436), stage B (0.1656+/-0.0329: 0.1572+/-0.0514), and stage C+D (0.2335+/-0.0748: 0.2219+/-0.0803). For PTEN expression, there was a significant difference among Dukes stage A, B, and C+D, and the level of PTEN expression was found to be significant higher in Dukes stage A or B than that of Dukes stage C or D. For HIF-1alpha expression, there was a significant difference between Dukes stage A and B, and the level of HIF-1alpha expression was found to be significantly higher in Dukes stage C+D than that of Dukes stage A or B. The VEGF expression had similar results as HIF-1alpha expression. In colorectal adenocarcinoma, decreased levels of PTEN were significantly associated with increased expression of HIF-1alpha mRNA (r=-0.36, P<0.05) and VEGF protein (r=-0.48, P<0.05) respectively. The levels of HIF-1 were positively correlated with VEGF expression (r=0.71, P<0.01).
Loss of PTEN expression and increased levels of HIF-1alpha and VEGF may play an important role in carcinogenesis and progression of colorectal adenocarcinoma.
探讨PTEN、缺氧诱导因子-1α（HIF-1α）及靶向基因VEGF在结直肠癌发生过程中的表达及意义。
选取71例结直肠肿瘤患者（9例结直肠腺瘤和62例结直肠癌）的标本，经福尔马林固定、石蜡包埋，检测所有标本中PTEN mRNA、HIF-1α mRNA及VEGF蛋白的表达。采用原位杂交法检测PTEN mRNA、HIF-1α mRNA，采用柠檬酸盐微波SP免疫组化法检测VEGF蛋白。
结直肠腺瘤与结直肠癌中PTEN、HIF-1α及VEGF的表达存在显著差异（P<0.05）。PTEN的表达水平随病理分期增加而降低。相反，HIF-1α和VEGF的表达随Dukes分期增加而升高，具体如下：A期（0.1029±0.0457：0.1207±0.0436）、B期（0.1656±0.0329：0.1572±0.0514）、C+D期（0.2335±0.0748：0.2219±0.0803）。PTEN的表达在Dukes A、B、C+D期之间存在显著差异，且Dukes A期或B期的PTEN表达水平显著高于Dukes C期或D期。HIF-1α的表达在Dukes A期和B期之间存在显著差异，且Dukes C+D期的HIF-1α表达水平显著高于Dukes A期或B期。VEGF的表达结果与HIF-1α相似。在结直肠癌中，PTEN水平降低分别与HIF-1α mRNA表达增加（r=-0.36，P<0.05）和VEGF蛋白表达增加（r=-0.48，P<0.05）显著相关。HIF-1水平与VEGF表达呈正相关（r=0.71，P<0.01）。
PTEN表达缺失及HIF-1α和VEGF水平升高可能在结直肠癌的发生和发展中起重要作用。
