Personalized Medicine, Pharmacogenomics, Therapeutic Optimization, INSERM UMR-S1147, Université Paris Descartes, Paris.
Department of Hepatogastroenterology and Gastrointestinal Oncology, Georges Pompidou Hospital, Assistance Publique-Hopitaux de Paris, Université Paris Descartes, Paris.
Ann Oncol. 2017 May 1;28(5):1032-1035. doi: 10.1093/annonc/mdx066.
Caudal-type homeobox transcription factor 2 (CDX2) is involved in colon cancer (CC) oncogenesis and has been proposed as a prognostic biomarker in patients with stage II or III CC.
We analyzed CDX2 expression in a series of 469 CC typed for the new international consensus molecular subtype (CMS) classification, and we confirmed results in a series of 90 CC.
Here, we show that lack of CDX2 expression is only present in the mesenchymal subgroup (CMS4) and in MSI-immune tumors (CMS1) and not in CMS2 and CMS3 colon cancer. Although CDX2 expression was a globally independent prognostic factor, loss of CDX2 expression is not associated with a worse prognosis in the CMS1 group, but is highly prognostic in CMS4 patients for both relapse free and overall survival. Similarly, lack of CDX2 expression was a bad prognostic factor in MSS patients, but not in MSI.
Our work suggests that combination of the consensual CMS classification and lack of CDX2 expression could be a useful marker to identify CMS4/CDX2-negative patients with a very poor prognosis.
尾部型同源盒转录因子 2（CDX2）参与结肠癌（CC）的发生，并且被提议作为 II 期或 III 期 CC 患者的预后生物标志物。
我们分析了 469 例按新的国际共识分子亚型（CMS）分类的 CC 中 CDX2 的表达，并在 90 例 CC 中验证了结果。
在这里，我们表明 CDX2 表达的缺失仅存在于间质亚组（CMS4）和微卫星不稳定性免疫肿瘤（CMS1）中，而不存在于 CMS2 和 CMS3 结肠癌中。尽管 CDX2 表达是一个全球独立的预后因素，但在 CMS1 组中，CDX2 表达的缺失与预后不良无关，但在 CMS4 患者中，无论是无复发生存还是总体生存，CDX2 表达的缺失均具有高度的预后意义。同样，CDX2 表达的缺失在 MSS 患者中是一个不良预后因素，但在 MSI 中则不然。
我们的工作表明，共识 CMS 分类与 CDX2 表达缺失的结合可能是识别 CMS4/CDX2 阴性患者预后极差的有用标志物。
