Horst David, Kriegl Lydia, Engel Jutta, Jung Andreas, Kirchner Thomas
Pathologisches Institut der Ludwig-Maximilians-Universität München, Germany.
Eur J Cancer. 2009 Jul;45(11):2034-40. doi: 10.1016/j.ejca.2009.04.004. Epub 2009 May 4.
Nuclear beta-catenin and CD133 are linked with two hallmarks of colon cancer, wingless-type mouse mammary tumour virus integration site (WNT)-pathway dysregulation and colon cancer stem cells (Co-CSCs), respectively. Both molecules may be related, as Co-CSCs were proposed to require activated WNT-signalling and as CD133 was postulated as a WNT/beta-catenin target gene. Herein, we investigated the expression of these markers on serial sections of 162 stage IIA colonic adenocarcinomas. We found that the expression of these molecules is statistically independent and that they mark distinct but overlapping subpopulations of the tumour cells. Moreover, we show that their combined evaluation can identify colon cancer cases with vastly reduced survival (hazard ratio (HR) 13.4, 95% confidence interval (CI): 4.7-38.2) and a high risk of tumour progression (HR 6.8, 95%CI: 3.1-15.0). In conclusion, the independence of these markers may on the one hand have implications for their presumed value to identify Co-CSCs; on the other hand it allows their combined analysis to become a powerful tool to identify high risk cases of stage IIA colon cancer.
细胞核β-连环蛋白和CD133分别与结肠癌的两个特征相关，即无翅型小鼠乳腺肿瘤病毒整合位点（WNT）信号通路失调和结肠癌干细胞（Co-CSCs）。这两种分子可能有关联，因为有人提出Co-CSCs需要激活的WNT信号，且CD133被假定为WNT/β-连环蛋白靶基因。在此，我们研究了这两种标志物在162例IIA期结肠腺癌连续切片上的表达情况。我们发现这些分子的表达在统计学上相互独立，且它们标记了肿瘤细胞中不同但有重叠的亚群。此外，我们表明，联合评估它们能够识别出存活期大幅缩短（风险比（HR）13.4，95%置信区间（CI）：4.7 - 38.2）且肿瘤进展风险高（HR6.8，95%CI：3.1 - 15.0）的结肠癌病例。总之，这些标志物的独立性一方面可能对它们在识别Co-CSCs方面的假定价值有影响；另一方面，这使得它们的联合分析成为识别IIA期结肠癌高危病例的有力工具。
