Introduction: Protein arginine deiminases (PADIs) are a family of enzymes that catalyse the post-translational modification of proteins. Association between PADI expression and clinicopathology, protein expression, and outcome was determined. Methods: PADI2 and PADI4 expression was assessed immunohistochemically in a cohort of colorectal cancer (CRC) patients. Results: CRC 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 the 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. Conclusion: High expression of cytoplasmic PADI2, PADI4, and nuclear PADI4 were associated with an increase in overall survival.
Pathobiology

中文翻译：

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蛋白精氨酸脱亚氨酶 2 和 4 在结直肠癌中的临床和预后意义

简介：蛋白质精氨酸脱亚胺酶 (PADI) 是催化蛋白质翻译后修饰的酶家族。确定了 PADI 表达与临床病理学、蛋白质表达和结果之间的关联。方法：通过免疫组织化学方法在结直肠癌 (CRC) 患者队列中评估 PADI2 和 PADI4 的表达。结果：结直肠癌组织表达不同水平的 PADI2，主要定位于细胞质并与患者存活率相关（ p= 0.005); 高表达将存活时间从 43.5 个月增加到 67.6 个月。细胞质 PADI2 的表达与核 β 连环蛋白、PADI4 和 α-烯醇化酶的表达相关。相比之下，核 PADI2 的表达与生存率下降相关 ( p = 0.010)，高表达将生存期从 76.4 个月降低到 42.9 个月。CRC 组织在细胞核和细胞质中表达不同水平的 PADI4。细胞质 PADI4 的表达与存活率相关 ( p = 0.001)，高表达将存活时间从 48.1 个月增加到 71.8 个月。细胞质 PADI4 的表达与核 β 连环蛋白、α-烯醇化酶的表达相关 ( p ≤ 0.0001, p= 0.002) 和凋亡相关蛋白 Bcl-2。核 PADI4 的表达也与生存率相关 ( p = 0.011)，核 PADI4 的高表达将生存时间从 55.4 个月增加到 74 个月。核 PADI4 的表达与 p53、α-烯醇化酶和 Bcl-2 相关。多变量分析显示TNM分期、细胞质PADI2和PADI4仍然是CRC的独立预后因素。PADI2和PADI4都是CRC良好的预后因素。结论：细胞质 PADI2、PADI4 和核 PADI4 的高表达与总生存期的增加相关。
病理学