S100 Calcium-Binding Protein P Predicts Early Recurrence and Poor Survival in Distal Cholangiocarcinoma: A Proteomics Study

Abstract

Distal cholangiocarcinoma (dCCA) is a rare malignancy with a poor prognosis, necessitating novel biomarkers for acute prognosis and optimal treatment selection. This study aimed to elucidate the proteomic landscape of dCCA and identify novel biomarkers associated with improved patient outcomes. Proteomic profiling was conducted on 18 surgical samples from patients with dCCA by using shotgun liquid chromatography with tandem mass spectrometry. Patients were categorized into early recurrence (n = 9) and nonearly recurrence (n = 9) groups. Validation was performed via immunohistochemical (IHC) analysis on an independent dCCA cohort of 26 tissue microarray samples. A total of 6804 proteins were identified, and differential expression and functional enrichment analyses revealed 219 upregulated proteins in the early recurrence group, associated with biological processes of the extracellular matrix and cellular interaction. Among these, S100 calcium-binding protein P (S100P) correlated with EZR, and LGALS3BP was significantly overexpressed in the early recurrence group. Furthermore, high S100P expression was identified as a strong independent risk factor for recurrence, with a hazard ratio (HR) of 4.55 (95% CI, 1.609-12.841, p = 0.004) and mortality (HR 4.99, 95% CI 1.794-12.880, p = 0.002). These findings identify S100P as a prognostic biomarker for dCCA, suggesting its clinical utility for postoperative risk stratification and patient management.