Peptidylarginine Deiminase Type 2 Predicts Tumor Progression and Poor Prognosis in Patients with Curatively Resected Biliary Tract Cancer

SIMPLE SUMMARY: Biliary tract cancer (BTC) is a highly aggressive malignancy with a poor prognosis; currently, limited biomarkers are available for early diagnosis and effective disease management. Therefore, it is essential to investigate reliable biomarkers for BTC patients. Peptidylarginine deiminase type 2 (PADI2) is a vital factor for post-translational modification (PTM) that catalyzes arginine to citrulline. It is crucial in several pathophysiological processes, such as autoimmune diseases and cancers. We evaluated the clinical significance of PADI2 expression in pathological stage I–III BTC patients. We observed that patients with high PADI2 protein expression are associated with poorer survival, including progress-free survival (PFS), disease-specific survival (DSS), and overall survival (OS). Our study highlighted, for the first time, a significant correlation between the PADI2 higher expression levels and unfavorable prognosis in BTC, which can be used to predict patients’ survival outcomes. ABSTRACT: (1) Background: PADI2 is a post-translational modification (PTM) enzyme that catalyzes citrullination, which then triggers autoimmune disease and cancer. This study aimed to evaluate the prognostic value of peptidylarginine deiminase 2 (PADI2) protein expression in biliary tract cancer (BTC) patients. (2) Methods: Using immunohistochemistry, the PADI2 protein expression in BTC tissues was analyzed. The correlations between PADI2 protein expression and clinicopathologic characteristics were analyzed using Chi-square tests. The Kaplan–Meier procedure was used for comparing survival distributions. We used Cox proportional hazards regression for univariate and multivariate analyses. From 2014 to 2020, 30 resected BTC patients were enrolled in this study. (3) Results: Patients with high PADI2 protein expression were associated with shorter progress-free survival (PFS; p = 0.041), disease-specific survival (DSS; p = 0.025), and overall survival (OS; p = 0.017) than patients with low PADI2 protein expression. (4) Conclusions: The results indicated that PADI2 protein expression was an independent poor prognostic factor for BTC patients regarding PFS, DSS, and OS.