CD44 and phosphorylated ERK1/2 coexpression predicts distant metastasis in colorectal cancer based on a study of 1137 Saudi patients

Cluster of differentiation 44 (CD44) is a transmembrane glycoprotein implicated in tumor progression and metastasis, while phosphorylated ERK1/2 (p-ERK1/2) plays central role in MAPK pathway-driven oncogenic signaling. We investigated the expression and clinical relevance of CD44 in colorectal cancer (CRC) and explored its synergistic interaction with p-ERK1/2 in predicting metastatic risk. Immunohistochemistry (IHC) for CD44 and p-ERK1/2 was performed in tissue microarray from 1,137 primary CRC cases. Associations with clinicopathological parameters and survival outcomes were analyzed using Chi-square tests, Kaplan-Meier curves and logistic regression models. CD44 was over expressed in 47.7% (542/1,137) cases and was significantly associated with lymph node metastasis (p = 0.0042), stage III disease (p = 0.0045), high-grade tumors (p = 0.0111), deficient mismatch repair status (p = 0.0007), high Ki-67 (p = 0.0051) and p-ERK1/2 expressions (p = 0.0012). However, CD44 alone did not predict survival outcomes (overall survival and disease-free survival). Co-expression of CD44 and p-ERK1/2 was observed in 284 cases (25.3%) and was significantly associated with stage III/IV disease (p = 0.0022), lymph node involvement (p = 0.0117) and metachronous distant metastasis (p = 0.0404). Co-expression emerged as an independent predictor of distant metastasis in multivariate analysis (Odds ratio = 1.73; 95% confidence interval = 1.11-2.69; p = 0.0149). CD44 and p-ERK1/2 co-expression defines a high-risk subset of CRC patients with increased metastatic potential. These findings highlight a clinically relevant biomarker axis that may aid in prognostic stratification and future therapeutic targeting.