The Prognostic and Predictive Utility of CDX2 in Colorectal Cancer

Caudal type homeobox transcription factor 2 (CDX2) is a protein expressed in the normal intestinal epithelium that is essential for regulating cell growth. It has been found to be downregulated or lost in a significant proportion of patients with colorectal cancer and can influence cancer behaviour and treatment response. Therefore, further research and assessment of CDX2 levels in tumour tissues is crucial for identifying potential markers that can select patients with worse outcomes and guide treatment decisions to improve survival. This study found that tumours with low CDX2 expression were associated with more aggressive features of cancer and worse outcomes for patients. However, giving additional chemotherapy after surgery to certain early-stage colon cancer patients with low CDX2 levels did not significantly improve survival. These findings support CDX2 as a marker for colorectal cancer prognosis, but more research is needed to determine its ability to predict chemotherapy outcomes. 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 (p < 0.001) and disease-free survival (p = 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 (p = 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.