Division of Molecular Genetics, German Cancer Research Center, University of Heidelberg, Heidelberg, Germany.
Pathology. 2011 Apr;43(3):220-7. doi: 10.1097/PAT.0b013e328344e391.
In colorectal cancer (CRC), CD133 expression is an independent prognostic marker associated with adverse clinical outcome. The CD133 epitope AC133 allowed isolating stem cells from normal and cancerous tissues, although its use in colon was questioned. We aimed to identify differences between AC133 and AC133 cells.
We analysed the gene expression profiles of EpCAM/CEA/AC133 and EpCAM/CEA/AC133 cells from primary CRC and liver metastasis tissues (n = 5). Immunohistochemistry confirmed these results in a validation set.
We identified 68 genes differentially expressed between both populations, including genes of notorious importance in CRC pathogenesis, and several candidates not previously shown to play a major role in CRC. Notably, EGR1 belonged to the most highly expressed genes in AC133 cells. In the validation set, the presence of EGR1 and CD133 correlated (r = 0.625). Since EGR1 regulates Wnt through up-regulation of TCF4, which induces stem cell marker LGR5, the potential association between LGR5, EGR1 and CD133 was investigated. The presence of LGR5 correlated with the presence of EGR1 and CD133. Strong signals for LGR5 were detected throughout tumour invasion fronts.
The study suggests a connection between CD133 and EGR1 and emphasises the importance of the EGR1/TCF4/CD133/LGR5 network in CRC.
在结直肠癌（CRC）中，CD133 表达是与不良临床结局相关的独立预后标志物。CD133 表位 AC133 允许从正常和癌组织中分离干细胞，尽管其在结肠中的应用受到质疑。我们旨在确定 AC133 和 AC133 细胞之间的差异。
我们分析了来自原发性 CRC 和肝转移组织的 EpCAM/CEA/AC133 和 EpCAM/CEA/AC133 细胞的基因表达谱（n=5）。免疫组织化学在验证集中证实了这些结果。
我们确定了这两种细胞群之间差异表达的 68 个基因，包括在 CRC 发病机制中具有重要意义的基因，以及几个以前未被证明在 CRC 中起主要作用的候选基因。值得注意的是，EGR1 是 AC133 细胞中表达最高的基因之一。在验证集中，EGR1 和 CD133 的存在呈正相关（r=0.625）。由于 EGR1 通过上调 TCF4 调节 Wnt，从而诱导干细胞标志物 LGR5，因此研究了 LGR5、EGR1 和 CD133 之间的潜在关联。LGR5 的存在与 EGR1 和 CD133 的存在相关。在肿瘤侵袭前沿检测到强烈的 LGR5 信号。
该研究表明 CD133 和 EGR1 之间存在联系，并强调了 EGR1/TCF4/CD133/LGR5 网络在 CRC 中的重要性。
