Liverpool Cancer Therapy Centre, Liverpool Hospital, Liverpool, NSW 2170, Australia.
School of Medicine, Western Sydney University, Locked Bag 1797, Penrith, NSW 2571, Australia.
Int J Mol Sci. 2024 Aug 8;25(16):8673. doi: 10.3390/ijms25168673.
Caudal type homeobox transcription factor 2 (CDX2) is a gastrointestinal cancer biomarker that regulates epithelial development and differentiation. Absence or low levels of CDX2 have been associated with poor prognosis and proposed as a chemotherapy response predictor. Tumour tissue samples from 668 patients with stage I-IV colorectal cancer were stained for CDX2 and stratified into two subgroups according to expression levels. Statistical tests were used to evaluate CDX2's relationship with survival and chemotherapy response. Of 646 samples successfully stained, 51 (7.9%) had low CDX2 levels, and 595 (92.1%) had high levels. Low CDX2 staining was associated with poor differentiation and the presence of lymphovascular or perineural invasion and was more common in colon and right-sided tumours. Overall survival ( < 0.001) and disease-free survival ( = 0.009) were reduced in patients with low CDX2 expression. Multivariable analysis validated CDX2 as an independent poor prognostic factor after excluding confounding variables. There was no statistically significant improvement in survival with adjuvant chemotherapy in stage II colon cancer ( = 0.11). In the rectal cohort, there was no relationship between CDX2 levels and therapy response. While confirming the prognostic utility of CDX2 in colorectal cancer, our study highlights that larger studies are required to confirm its utility as a predictive chemotherapy biomarker, especially in left-sided and rectal cancers.
尾型同源盒转录因子 2（CDX2）是一种胃肠道癌症生物标志物，可调节上皮细胞的发育和分化。CDX2 的缺失或低水平与预后不良相关，并被提出作为化疗反应预测因子。对 668 例 I-IV 期结直肠癌患者的肿瘤组织样本进行 CDX2 染色，并根据表达水平分为两组。统计学检验用于评估 CDX2 与生存和化疗反应的关系。在成功染色的 646 个样本中，有 51 个（7.9%）CDX2 水平低，595 个（92.1%）水平高。低 CDX2 染色与分化不良以及存在淋巴血管或神经周围侵犯有关，在结肠和右侧肿瘤中更为常见。低 CDX2 表达的患者总生存（<0.001）和无病生存（=0.009）降低。多变量分析在排除混杂因素后证实 CDX2 是独立的预后不良因素。在 II 期结肠癌中，辅助化疗对生存没有统计学意义的改善（=0.11）。在直肠队列中，CDX2 水平与治疗反应之间没有关系。虽然本研究证实了 CDX2 在结直肠癌中的预后效用，但强调需要更大规模的研究来证实其作为预测化疗生物标志物的效用，尤其是在左侧和直肠癌症中。
