Integrating WNT10B Into a Prognostic Model to Stratify Survival Risk and Immune Phenotype in Colon Cancer

Background The optimization of therapeutic safety in oncology requires precise biomarkers to stratify patients and anticipate treatment interactions. While dysregulation of the Wnt pathway is a hallmark of colon cancer, the clinical and immunological significance of noncanonical Wnt ligands, particularly WNT10B, remains poorly defined, limiting their utility in personalized risk assessment. Methods We conducted an integrative bioinformatics analysis using The Cancer Genome Atlas (TCGA) colon adenocarcinoma (COAD) cohort ( n = 478). WNT10B expression was analyzed for its association with clinicopathological features, overall survival (OS), and disease‐specific survival (DSS). Multivariate Cox regression was used to determine its independent prognostic value. Immune cell infiltration was estimated using CIBERSORTx and ssGSEA algorithms. A prognostic nomogram incorporating WNT10B was developed and validated. Results WNT10B was significantly upregulated in tumor tissues and associated with advanced T stage ( p = 0.022). High WNT10B expression predicted inferior OS (HR = 3.304, p = 0.010) and DSS (HR = 3.879, p = 0.014), remaining an independent prognostic factor after adjusting for age and TNM stage. Tumors with high WNT10B exhibited an immunosuppressive microenvironment, characterized by increased M2 macrophage infiltration and reduced CD8 + T cell abundance, which has been well‐acknowledged as a phenotype with reduced immunotherapy response in previous studies. The WNT10B ‐incorporated nomogram showed robust calibration for predicting 1‐, 3‐, and 5‐year survival. Conclusion Our study establishes WNT10B as a novel, independent prognostic biomarker in colon cancer, directly linked to an immunosuppressive tumor microenvironment.