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Article Open Access

Role of CDX2 in the prognosis of colorectal cancer across stages 0‑IV

  • Authors:
    • Guojun Tong
    • Hai Qian
    • Yuefeng Fei
    • Sheng Yu
    • Kun Guo
    • Wenwen Yu
    • Jing Li
    • Sicheng Yan
  • View Affiliations / Copyright

    Affiliations: Department of Colorectal Surgery, Huzhou Central Hospital, Affiliated Central Hospital of Huzhou University, Huzhou, Zhejiang 313003, P.R. China, Department of General Surgery, Huzhou Central Hospital, Affiliated Central Hospital of Huzhou University, Huzhou, Zhejiang 313003, P.R. China, Department of Gastroenterology, Huzhou Central Hospital, Affiliated Central Hospital of Huzhou University, Huzhou, Zhejiang 313003, P.R. China, Central Laboratory Department, Huzhou Central Hospital, Affiliated Central Hospital of Huzhou University, Huzhou, Zhejiang 313003, P.R. China
    Copyright: © Tong et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Article Number: 227
    |
    Published online on: April 8, 2026
       https://doi.org/10.3892/ol.2026.15581
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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.
View Figures

Figure 1

Representative images of CDX2
expression in colorectal cancer. (A) CDX2 absent/low expression at
×200 magnification. (B) CDX2 absent/low expression at ×400
magnification. (C) CDX2 high expression at ×200 magnification. (D)
CDX2 high expression at ×400 magnification. CDX2, caudal-type
homeobox 2.

Figure 2

Correlation and relational analysis
of CDX2. (A) Spearman correlation heatmap between CDX2 and
variables including TP53, TCEA, MSI, Ecadherin, Top2,
differentiation and TNM1 stage, generated using R 4.4.1. Blue
indicates positive correlations, red indicates negative
correlations and white indicates nearzero correlation. Asterisks
denote statistical significance: *P<0.05; **P<0.01;
***P<0.001. (B) Relation map between CDX2 expression (absent/low
vs. high), TNM1 stage and differentiation, generated using SPSS 29.
Circle size corresponds to the number of cases; line thickness
indicates the strength of association. CDX2, caudal-type homeobox
2; MSI, microsatellite instability; TCEA, tumour carcinoembryonic
antigen; TP53, tumour p53; TNM, tumour-node-metastasis; Top2,
topoisomerase II α.

Figure 3

Hierarchical cluster analysis with
coefficient table. Systematic cluster analysis was performed using
SPSS 29. The results indicate that CDX2 clusters most closely with
MSI (coefficient=227), followed by the linkage between MSI and TCEA
(coefficient=475), and finally between MSI and TNM1
(coefficient=866). CDX2, caudal-type homeobox 2; MSI,
microsatellite instability; TCEA, tumour carcinoembryonic antigen;
TNM, tumour-node-metastasis.

Figure 4

Kaplan-Meier curves for 5-year OS
stratified by CDX2 expression across colorectal cancer stages and
in the pooled analysis, with numberatrisk tables. (A) Stage 0 and I
(P=0.11). (B) Stage II (P=0.01). (C) Stage III (P<0.001). (D)
Stage IV (P=0.69). (E) Pooledstage analysis (P<0.001). OS,
overall survival; HR, hazard ratio.

Figure 5

Kaplan-Meier curves for 5 year DFS
stratified by CDX2 expression across colorectal cancer stages and
in the pooled analysis, with numberatrisk tables. (A) Stage 0 and I
(P=0.16). (B) Stage II (P=0.04). (C) Stage III (P<0.001). (D)
Stage IV (P=0.94). (E) Pooledstage analysis (P<0.001). CDX2,
caudal-type homeobox 2; DFS, disease-free survival; HR, hazard
ratio.
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Copy and paste a formatted citation
Spandidos Publications style
Tong G, Qian H, Fei Y, Yu S, Guo K, Yu W, Li J and Yan S: Role of CDX2 in the prognosis of colorectal cancer across stages 0‑IV. Oncol Lett 31: 227, 2026.
APA
Tong, G., Qian, H., Fei, Y., Yu, S., Guo, K., Yu, W. ... Yan, S. (2026). Role of CDX2 in the prognosis of colorectal cancer across stages 0‑IV. Oncology Letters, 31, 227. https://doi.org/10.3892/ol.2026.15581
MLA
Tong, G., Qian, H., Fei, Y., Yu, S., Guo, K., Yu, W., Li, J., Yan, S."Role of CDX2 in the prognosis of colorectal cancer across stages 0‑IV". Oncology Letters 31.6 (2026): 227.
Chicago
Tong, G., Qian, H., Fei, Y., Yu, S., Guo, K., Yu, W., Li, J., Yan, S."Role of CDX2 in the prognosis of colorectal cancer across stages 0‑IV". Oncology Letters 31, no. 6 (2026): 227. https://doi.org/10.3892/ol.2026.15581
Copy and paste a formatted citation
x
Spandidos Publications style
Tong G, Qian H, Fei Y, Yu S, Guo K, Yu W, Li J and Yan S: Role of CDX2 in the prognosis of colorectal cancer across stages 0‑IV. Oncol Lett 31: 227, 2026.
APA
Tong, G., Qian, H., Fei, Y., Yu, S., Guo, K., Yu, W. ... Yan, S. (2026). Role of CDX2 in the prognosis of colorectal cancer across stages 0‑IV. Oncology Letters, 31, 227. https://doi.org/10.3892/ol.2026.15581
MLA
Tong, G., Qian, H., Fei, Y., Yu, S., Guo, K., Yu, W., Li, J., Yan, S."Role of CDX2 in the prognosis of colorectal cancer across stages 0‑IV". Oncology Letters 31.6 (2026): 227.
Chicago
Tong, G., Qian, H., Fei, Y., Yu, S., Guo, K., Yu, W., Li, J., Yan, S."Role of CDX2 in the prognosis of colorectal cancer across stages 0‑IV". Oncology Letters 31, no. 6 (2026): 227. https://doi.org/10.3892/ol.2026.15581
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