Li Tianhong, Yang Wancai, Li Maomi, Byun Do-Sun, Tong Chang, Nasser Shannon, Zhuang Min, Arango Diego, Mariadason John M, Augenlicht Leonard H
Department of Pathology, University of Illinois at Chicago, Chicago, IL, USA.
Mol Nutr Food Res. 2008 Nov;52(11):1289-99. doi: 10.1002/mnfr.200700331.
To identify candidate genes involved in the development of colorectal cancer, we used cDNA microarrays to analyze gene expression differences between human colorectal tumors and paired adjacent normal mucosa. We identified approximately 3.5-fold significant downregulation of selenium-binding protein 1 (SBP1) in colorectal tumors compared to normal mucosa (p = 0.003). Importantly, stage III colorectal cancer patients with low tumor-SBP1 expression had significantly shorter disease-free and overall survival as compared with those patients with high tumor-SBP1 expression (p = 0.04 and 0.03, respectively). We further characterized the role of SBP1 in colorectal cancer in vivo and in vitro. In normal tissue, SBP1 was maximally expressed in terminally differentiated epithelial cells on the luminal surface of crypts in the large intestine. Consistent with this in vivo localization, SBP1 was upregulated during in vitro colonic cell differentiation along the absorptive (Caco-2) and secretory (HT29 Clones 16E and 19A) cell lineages. Downregulation (approximately 50%) of SBP1 expression by small interfering RNA in colonic cancer cells was associated with reduced expression of another epithelial differentiation marker, carcinoembryonic antigen (CEA), although PCNA and p21(WAF1/cip1 )expression were not altered. These data demonstrate that higher expression of SBP1 is associated with differentiation of the normal colonic epithelia and may be a positive prognostic factor for survival in stage III colorectal carcinoma.
为了鉴定参与结直肠癌发生发展的候选基因，我们使用cDNA微阵列分析人类结直肠癌组织与其配对的相邻正常黏膜之间的基因表达差异。我们发现，与正常黏膜相比，结直肠癌组织中硒结合蛋白1（SBP1）显著下调约3.5倍（p = 0.003）。重要的是，肿瘤SBP1低表达的III期结直肠癌患者与肿瘤SBP1高表达的患者相比，无病生存期和总生存期显著缩短（分别为p = 0.04和0.03）。我们进一步在体内和体外研究了SBP1在结直肠癌中的作用。在正常组织中，SBP1在大肠隐窝腔表面的终末分化上皮细胞中表达最高。与这种体内定位一致，在体外沿吸收性（Caco-2）和分泌性（HT29 Clones 16E和19A）细胞谱系进行结肠细胞分化过程中，SBP1表达上调。在结肠癌细胞中，通过小干扰RNA使SBP1表达下调（约50%）与另一种上皮分化标志物癌胚抗原（CEA）表达降低有关，尽管增殖细胞核抗原（PCNA）和p21（WAF1/cip1）的表达未改变。这些数据表明，SBP1的高表达与正常结肠上皮的分化相关，可能是III期结直肠癌患者生存的一个阳性预后因素。
