Cancer Research Program, Hospital del Mar Research Institute (IMIM), Barcelona, Spain.
Cancer Evolution and Genome Instability Laboratory, University College London Cancer Institute, London, UK.
Cancer Treat Rev. 2023 Dec;121:102643. doi: 10.1016/j.ctrv.2023.102643. Epub 2023 Oct 12.
Adjuvant chemotherapy following surgical intervention remains the primary treatment option for patients with localized colorectal cancer (CRC). However, a significant proportion of patients will have an unfavorable outcome after current forms of chemotherapy. While reflecting the increasing complexity of CRC, the clinical application of molecular biomarkers provides information that can be utilized to guide therapeutic strategies. Among these, caudal-related homeobox transcription factor 2 (CDX2) emerges as a biomarker of both prognosis and relapse after therapy. CDX2 is a key transcription factor that controls intestinal fate. Although rarely mutated in CRC, loss of CDX2 expression has been reported mostly in right-sided, microsatellite-unstable tumors and is associated with aggressive carcinomas. The pathological assessment of CDX2 by immunohistochemistry can thus identify patients with high-risk CRC, but the evaluation of CDX2 expression remains challenging in a substantial proportion of patients. In this review, we discuss the roles of CDX2 in homeostasis and CRC and the alterations that lead to protein expression loss. Furthermore, we review the clinical significance of CDX2 assessment, with a particular focus on its current use as a biomarker for pathological evaluation and clinical decision-making. Finally, we attempt to clarify the molecular implications of CDX2 deficiency, ultimately providing insights for a more precise evaluation of CDX2 protein expression.
手术干预后的辅助化疗仍然是局部结直肠癌（CRC）患者的主要治疗选择。然而，相当一部分患者在接受目前形式的化疗后会出现不良预后。虽然反映了结直肠癌的日益复杂性，但分子生物标志物的临床应用提供了可用于指导治疗策略的信息。其中，尾型同源盒转录因子 2（CDX2）是治疗后预后和复发的生物标志物。CDX2 是控制肠道命运的关键转录因子。虽然在 CRC 中很少发生突变，但 CDX2 表达缺失主要发生在右侧、微卫星不稳定的肿瘤中，与侵袭性癌有关。因此，免疫组织化学法对 CDX2 的病理评估可以识别出具有高风险 CRC 的患者，但在相当一部分患者中，CDX2 表达的评估仍然具有挑战性。在这篇综述中，我们讨论了 CDX2 在体内平衡和 CRC 中的作用以及导致其蛋白表达缺失的改变。此外，我们还综述了 CDX2 评估的临床意义，特别关注其作为病理评估和临床决策的生物标志物的当前用途。最后，我们试图阐明 CDX2 缺失的分子意义，最终为更精确地评估 CDX2 蛋白表达提供了思路。
