The clinical and prognostic significance of Protein Arginine Deiminase 2 and 4 (PADI2 & PADI4) in colorectal cancer

Abstract

ABSTRACTAimsProtein arginine deiminase (PADs) are a family of enzymes that catalyse the post translational modification (PTM) of proteins. Association between PAD expression with clinicopathology, protein expression and outcome was determined.MethodsPADI2 and PADI4 expression was assessed immunohistochemically in a cohort of CRC patients.ResultsCRC tissues expressed variable levels of PADI2 which was mainly localised in the cytoplasm and correlated with patient survival (p=0.005); high expression increased survival time from 43.5 to 67.6 months. Expression of cytoplasmic PADI2 correlated with expression of nuclear β catenin, PADI4 and alpha-enolase. In contrast expression of nuclear PADI2 correlated with a decrease in survival (p=0.010), with high expression decreasing survival from 76.4 to 42.9 months. CRC tissues expressed variable levels of PADI4 in both the nucleus and cytoplasm. Expression of cytoplasmic PADI4 correlated with survival (p=0.001) with high expression increasing survival time from 48.1 to 71.8 months. Expression of cytoplasmic PADI4 correlated with expression of, nuclear β catenin, alpha-enolase (p≤0.0001, p=0.002) and the apoptotic related protein, Bcl-2. Expression of nuclear PADI4 also correlated with survival (p=0.011) with high expression of nuclear PADI4 increasing survival time from 55.4 to 74 months. Expression of nuclear PADI4 correlated with p53, alpha-enolase and Bcl-2. Multivariate analysis showed that TNM stage, cytoplasmic PADI2 and PADI4 remained independent prognostic factors in CRC. Both PADI2 and PADI4 are good prognostic factors in CRC.ConclusionsHigh expression of cytoplasmic PADI2, PADI4 and nuclear PADI4 were associated with an increase in overall survival.