Wang Shuang, Zhou Jun, Wang Xiao-Yan, Hao Jun-Mei, Chen Juan-Zhi, Zhang Xiang-Mei, Jin He, Liu Li, Zhang Yan-Fei, Liu Jinsong, Ding Yan-Qing, Li Jian-Ming
Department of Pathology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, People's Republic of China.
J Pathol. 2009 Sep;219(1):114-22. doi: 10.1002/path.2575.
To identify novel biomarkers of metastasis of colorectal cancer (CRC), we developed an orthotopic implantation model of murine CRC and selected in vivo M5, a subclone of the SW480 CRC cell line with enhanced potential for metastasis to the liver. We compared the differences in the gene expression profiles between M5 and SW480 cells using gene expression profiling. We found that expression of special AT-rich sequence-binding protein 2 (SATB2) was down-regulated in M5 cells. Immunohistochemical analysis of 146 colorectal tumour samples showed that underexpression of SATB2 was strongly correlated with poor prognosis, tumour invasion, lymph node metastasis, distant metastasis, and Dukes' classification for CRC. Univariate and multivariate survival analyses further showed that SATB2 expression was a potential favourable prognostic factor for CRC. These results demonstrated not only that SATB2 is a potential novel prognostic factor for CRC, but also that selection of a highly metastatic clone of SW480 in vivo coupled with gene expression profiling is a powerful approach to identifying prognostic markers for CRC.
为了鉴定结直肠癌(CRC)转移的新型生物标志物,我们建立了小鼠CRC原位植入模型,并筛选出体内M5,它是SW480 CRC细胞系的一个亚克隆,具有增强的肝转移潜能。我们使用基因表达谱分析比较了M5和SW480细胞之间基因表达谱的差异。我们发现富含特殊AT序列结合蛋白2(SATB2)在M5细胞中的表达下调。对146例结直肠肿瘤样本进行免疫组化分析显示,SATB2低表达与CRC的预后不良、肿瘤侵袭、淋巴结转移、远处转移及Dukes分期密切相关。单因素和多因素生存分析进一步表明,SATB2表达是CRC潜在的有利预后因素。这些结果不仅表明SATB2是CRC潜在的新型预后因素,而且表明在体内选择SW480的高转移克隆并结合基因表达谱分析是鉴定CRC预后标志物的有效方法。