Abstract
<h3>ABSTRACT</h3> <h3>Aims</h3> Protein 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. <h3>Methods</h3> PADI2 and PADI4 expression was assessed immunohistochemically in a cohort of CRC patients. <h3>Results</h3> CRC tissues expressed variable levels of PADI2 which was mainly localised in the cytoplasm and correlated with patient survival (<i>p</i>=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 (<i>p</i>=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 (<i>p</i>=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 (<i>p</i>≤0.0001, <i>p</i>=0.002) and the apoptotic related protein, Bcl-2. Expression of nuclear PADI4 also correlated with survival (<i>p</i>=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. <h3>Conclusions</h3> High expression of cytoplasmic PADI2, PADI4 and nuclear PADI4 were associated with an increase in overall survival.
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