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Multicenter validation of CEACAM6 and FOXP3 as robust prognostic biomarkers in colon cancer: Combined immunohistochemical and transcriptomic analysis

  • Authors:
    • Yingying Liu
    • Jianxin Ye
    • Jinzhao Ma
    • Xingxiao Pan
  • View Affiliations / Copyright

    Affiliations: Department of Gastroenterology, Affiliated Hospital of Jiangnan University, Wuxi, Jiangsu 214000, P.R. China, Department of Gastroenterology, First Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215006, P.R. China, Department of Reproductive Medicine, Eastern Theater Command General Hospital, Nanjing, Jiangsu 210002, P.R. China, Department of Gastroenterology, Jiangsu Provincial Veterans Hospital, Wuxi, Jiangsu 214000, P.R. China
    Copyright: © Liu et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Article Number: 102
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    Published online on: September 24, 2025
       https://doi.org/10.3892/mco.2025.2897
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Abstract

Colon cancer remains a leading cause of cancer-related mortality worldwide, with metastatic disease exhibiting particularly poor prognosis. To identify robust prognostic biomarkers, the present multicenter study employed immunohistochemistry and reverse transcription‑quantitative PCR to evaluate CEACAM6 and FOXP3 expression in 301 colon cancer specimens from three tertiary hospitals in China, analyzing their associations with tumor‑infiltrating lymphocytes, clinicopathological features and patient outcomes. Key findings revealed that early‑stage (I‑II) tumors exhibited significantly higher infiltration of CD3+, CD8+ and CD45RO+ T cells compared with advanced‑stage (III‑IV) tumors (P<0.001), while FOXP3 and CEACAM6 expression were significantly elevated in late‑stage and poorly differentiated tumors (P<0.001). Notably, CEACAM6 overexpression correlated inversely with CD3+, CD8+ and CD45RO+ T‑cell infiltration but positively with FOXP3+ Tregs. Transcriptomic analysis further confirmed upregulation of CEACAM6 and FOXP3 mRNA in advanced‑stage tumors (P<0.001). Kaplan‑Meier survival analysis demonstrated that high CEACAM6 and FOXP3 expression were associated with significantly shorter overall survival (P<0.001). Multivariate Cox regression identified TNM stage, tumor differentiation, CEACAM6 and FOXP3 as independent prognostic factors. The present study provides robust multicenter validation of CEACAM6 and FOXP3 as critical biomarkers in colon cancer, highlighting their roles in immune evasion and tumor progression. These findings support their potential integration into clinical risk stratification and the development of targeted immunotherapies. Further mechanistic and prospective studies are warranted to explore their therapeutic applications.
View Figures

Figure 1

Representative immunohistochemical
staining of CD3, CD4, CD8, CD45RO, CEACAM6 and FOXP3 in colon
cancer (magnification, x400). Scale bar, 50 µm. (A) Well/moderately
differentiated; (B) Poorly differentiated.

Figure 2

mRNA expression levels of CD3, CD4,
CD8, CD45RO, CEACAM6 and FOXP3 in stage I-II vs. stage III-IV colon
cancer.

Figure 3

Association between survival time and
expression levels of CD3, CD4, CD8, CD45RO, CEACAM6 and FOXP3 in
patients with colon cancer. KaplanMeier curves for overall survival
in patients with colon cancer. The P-values were determined using
logrank test. -ve, negative/weak expression; +ve, strong
expression.

Figure 4

Association of survival outcomes with
tumor histological grade and TNM staging classification.
Kaplan-Meier curves for overall survival in patients with colon
cancer. The Pvalues were determined using logrank test. -ve,
negative/weak expression; +ve, strong expression.

Figure 5

Forest plot displaying hazard ratios
with 95% confidence intervals for various prognostic factors in the
study. All P-values indicate statistically significant associations
with the outcome.
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Copy and paste a formatted citation
Spandidos Publications style
Liu Y, Ye J, Ma J and Pan X: Multicenter validation of CEACAM6 and FOXP3 as robust prognostic biomarkers in colon cancer: Combined immunohistochemical and transcriptomic analysis. Mol Clin Oncol 23: 102, 2025.
APA
Liu, Y., Ye, J., Ma, J., & Pan, X. (2025). Multicenter validation of CEACAM6 and FOXP3 as robust prognostic biomarkers in colon cancer: Combined immunohistochemical and transcriptomic analysis. Molecular and Clinical Oncology, 23, 102. https://doi.org/10.3892/mco.2025.2897
MLA
Liu, Y., Ye, J., Ma, J., Pan, X."Multicenter validation of CEACAM6 and FOXP3 as robust prognostic biomarkers in colon cancer: Combined immunohistochemical and transcriptomic analysis". Molecular and Clinical Oncology 23.6 (2025): 102.
Chicago
Liu, Y., Ye, J., Ma, J., Pan, X."Multicenter validation of CEACAM6 and FOXP3 as robust prognostic biomarkers in colon cancer: Combined immunohistochemical and transcriptomic analysis". Molecular and Clinical Oncology 23, no. 6 (2025): 102. https://doi.org/10.3892/mco.2025.2897
Copy and paste a formatted citation
x
Spandidos Publications style
Liu Y, Ye J, Ma J and Pan X: Multicenter validation of CEACAM6 and FOXP3 as robust prognostic biomarkers in colon cancer: Combined immunohistochemical and transcriptomic analysis. Mol Clin Oncol 23: 102, 2025.
APA
Liu, Y., Ye, J., Ma, J., & Pan, X. (2025). Multicenter validation of CEACAM6 and FOXP3 as robust prognostic biomarkers in colon cancer: Combined immunohistochemical and transcriptomic analysis. Molecular and Clinical Oncology, 23, 102. https://doi.org/10.3892/mco.2025.2897
MLA
Liu, Y., Ye, J., Ma, J., Pan, X."Multicenter validation of CEACAM6 and FOXP3 as robust prognostic biomarkers in colon cancer: Combined immunohistochemical and transcriptomic analysis". Molecular and Clinical Oncology 23.6 (2025): 102.
Chicago
Liu, Y., Ye, J., Ma, J., Pan, X."Multicenter validation of CEACAM6 and FOXP3 as robust prognostic biomarkers in colon cancer: Combined immunohistochemical and transcriptomic analysis". Molecular and Clinical Oncology 23, no. 6 (2025): 102. https://doi.org/10.3892/mco.2025.2897
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