Kim Hyunki, Kang Hyun Ju, You Kwon Tae, Kim Se Hoon, Lee Kang Young, Kim Tae Il, Kim Chul, Song Si Young, Kim Hye-Jung, Lee Cheolju, Kim Hoguen
Department of Pathology, Yonsei University College of Medicine, Seoul, Korea.
Proteomics. 2006 Jun;6(11):3466-76. doi: 10.1002/pmic.200500629.
The purpose of this study was to analyze altered protein expression in cancer tissues and determine its relationship to prognosis in colorectal carcinomas. We performed proteomic expression analysis on 14 colorectal carcinomas and matched nontumorous colonic mucosa by 2-DE and MALDI-TOF-MS. Comparative analysis of the respective spot patterns on 2-DE showed 14 spots that were markedly changed in the colorectal carcinomas. Among them, selenium-binding protein 1 (SELENBP1) was markedly decreased in 12 (85%) carcinomas. The reduced expression of SELENBP1 was further supported by Western blot analysis and immunohistochemistry. Suppression of SELENBP1 was further analyzed in another eight-paired adenomas and carcinomas from the same patients using Western blot analysis and immunohistochemistry, and revealed that one adenoma and seven carcinomas exhibited markedly reduced SELENBP1 expression. Patients with low levels of SELENBP1 expression had significantly lower overall survival rates (72 vs. 85%, p = 0.021) among the 240 stages II and III colorectal carcinomas by using tissue microarray analysis. Our findings indicate that suppression of SELENBP1 is a frequent and late event in colorectal carcinogenesis, and may contribute to the rapid progression of colorectal carcinoma.
本研究的目的是分析癌组织中蛋白质表达的改变，并确定其与结直肠癌预后的关系。我们通过二维电泳（2-DE）和基质辅助激光解吸电离飞行时间质谱（MALDI-TOF-MS）对14例结直肠癌及配对的非肿瘤性结肠黏膜进行了蛋白质组学表达分析。二维电泳上各自斑点模式的比较分析显示，结直肠癌中有14个斑点发生了明显变化。其中，12例（85%）癌组织中硒结合蛋白1（SELENBP1）明显减少。蛋白质免疫印迹分析和免疫组织化学进一步证实了SELENBP1的表达降低。使用蛋白质免疫印迹分析和免疫组织化学对同一患者的另外8对腺瘤和癌组织中SELENBP1的抑制情况进行了进一步分析，结果显示1例腺瘤和7例癌组织中SELENBP1表达明显降低。通过组织芯片分析，在240例II期和III期结直肠癌患者中，SELENBP1表达水平低的患者总生存率显著较低（72%对85%，p = 0.021）。我们的研究结果表明，SELENBP1的抑制是结直肠癌发生过程中常见的晚期事件，可能促进结直肠癌的快速进展。
