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The Pathologist / Issues / 2025 / October / New Biomarker Duo Predicts Colorectal Cancer Outcomes
Oncology Precision medicine Biochemistry and molecular biology Molecular Pathology Research and Innovations

New Biomarker Duo Predicts Colorectal Cancer Outcomes

Researchers found that p21 and epidermal growth factor receptor expression levels influence colorectal cancer prognosis.

By Kathryn Wighton 10/21/2025 News 2 min read

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Credit: Adobe Stock

High p21 expression was linked to longer overall survival, while elevated epidermal growth factor receptor levels predicted poorer outcomes in patients with colorectal cancer, according to a recent study.

In the study, published in the Journal of Clinical Pathology, researchers investigated the clinicopathological and prognostic roles of p21 and epidermal growth factor receptor (EGFR) in colorectal cancer (CRC). They examined 12,319 Chinese patients with histologically confirmed CRC treated between January 2008 and December 2020, aiming to clarify the association between these biomarkers and patient outcomes.

The researchers used immunohistochemistry to quantify p21 and EGFR expression in resected tumor specimens. Staining intensity and the proportion of positive cells were evaluated and classified as negative, weakly positive, or positive. Data were analyzed using SPSS (version 25.0) and R (version 4.2.1). Correlations between biomarker expression and clinicopathological features were assessed with χ² and Spearman analyses, while overall survival (OS) was evaluated using Kaplan-Meier curves and Cox proportional hazards models.

Among the 12,319 patients (4,926 men and 7,393 women; mean age, 59.46 years), 33 percent of CRC specimens were negative for p21, 9 percent were weakly positive, and 58 percent were positive. For EGFR, 40 percent were negative, 21 percent weakly positive, and 39 percent positive. Immunostaining showed nuclear localization for p21 and membranous localization for EGFR. Spearman’s analysis identified a weak but significant positive correlation between p21 and EGFR expression (r=0.11; p<0.001).

The differential expression of p21 was significantly associated with tumor site, mucinous subtype, lymphovascular and perineural invasion, circumferential resection margin status, and advanced T, N, and TNM stages (p<0.05). EGFR expression correlated with mucinous subtype, tumor differentiation, lymphovascular and perineural invasion, tumor size, T and N stages, TNM stage, and BRAF mutation (p<0.05).

Survival analyses demonstrated that patients with high p21 expression had longer OS compared with those with low expression (p=0.004), whereas high EGFR expression was associated with shorter OS (p=0.009). Multivariate Cox regression identified age 50 years or more, poor differentiation, lymphovascular invasion, perineural invasion, tumor size 4 cm or more, advanced TNM stage, and low p21 expression as independent prognostic factors (p<0.05).

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Kathryn Wighton

Editor, Conexiant

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