Abstract
Caudal-type homeobox 2 (CDX2) proteins function as tumour suppressors in colorectal cancer (CRC), but their prognostic value remains controversial. In the present study, a total of 453 eligible patients diagnosed with CRC and having undergone surgery between January 2017 and January 2020 were included after applying exclusion criteria. CDX2 expression was classified as either absent/low (negative or +) or high (++ or +++). Clinicopathological characteristics, 5-year overall survival (OS) and disease-free survival (DFS) were compared across groups using Kaplan-Meier analysis with log-rank tests. Associations between categorical variables were assessed via Spearman's correlations, while univariate and multivariate analyses were performed using Cox regression models. CDX2 expression was only correlated with tumour-node-metastasis (TNM) stage (P=0.001). Tumour carcinoembryonic antigen expression was associated with E-cadherin (P<0.01) and microsatellite instability (P<0.01). High CDX2 expression was associated with significantly improved OS [stage II: P=0.013; hazard ratio (HR)=0.472; 95% CI, 0.257-0.867; stage III: P<0.001; HR=0.413; 95% CI, 0.271-0.628] and DFS (stage II: P=0.042; HR=0.606; 95% CI, 0.370-0.994; stage III: P<0.001; HR=0.468; 95% CI, 0.334-0.655). In the pooled-stage analysis, high CDX2 expression was also associated with improved OS (HR=0.511; 95% CI, 0.371-0.703) and DFS (HR=0.581; 95% CI, 0.448-0.753), with all pooled P-values <0.001. Cox regression identified chemotherapy, TNM stage, differentiation status, Ecadherin expression and CDX2 expression as independent prognostic factors. In conclusion, high CDX2 expression is associated with favourable prognosis in stages II and III CRC and represents an independent prognostic marker for both OS and DFS.