Downregulation of the Deiminase PADI2 Is an Early Event in Colorectal Carcinogenesis and Indicates Poor Prognosis
Downregulation of the Deiminase PADI2 Is an Early Event in Colorectal Carcinogenesis and Indicates Poor Prognosis
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DOI：
10.1158/1541-7786.mcr-16-0034
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发表时间：
2016-09-01
影响因子：
5.2
通讯作者：
Buschbeck, Marcus
中科院分区：
文献类型：
--
作者：
Cantarino, Neus;Musulen, Eva;Buschbeck, Marcus
肽基精氨酸脱亚胺酶（PADI）是一类催化翻译后修饰将精氨酸残基转化为瓜氨酸的酶。本研究探讨了PADIs在结直肠癌发病中的作用。具体来说，我们分析了98例结直肠癌患者标本与匹配的邻近粘膜和50例无癌供体对照的RNA表达及其与生存率的关系。关键结果在具有匹配邻近粘膜的独立肿瘤集合中得到验证，并通过挖掘公开可用的表达数据集。通过细胞系免疫印迹或免疫组化对患者标本进行蛋白表达分析，进一步包括24例腺癌伴伴不典型增生和11例活动性溃疡性结肠炎。这些数据表明，PADI2是结肠黏膜中主要表达的PADI酶，在分化过程中表达上调。PADI2在结直肠癌中表达低或不表达。通常，这种情况已经发生在低度发育不良阶段。粘膜PADI2在溃疡性结肠炎中的表达也很低。PADI2在肿瘤及邻近粘膜中的表达水平与差异生存相关，低表达与预后差相关。(c) 2016年aacr。
Peptidyl arginine deiminases (PADI) are a family of enzymes that catalyze the poorly understood posttranslational modification converting arginine residues into citrullines. In this study, the role of PADIs in the pathogenesis of colorectal cancer was investigated. Specifically, RNA expression was analyzed and its association with survival in a cohort of 98 colorectal cancer patient specimens with matched adjacent mucosa and 50 controls from donors without cancer. Key results were validated in an independent collection of tumors with matched adjacent mucosa and by mining of a publicly available expression data set. Protein expression was analyzed by immunoblotting for cell lines or IHC for patient specimens that further included 24 cases of adenocarcinoma with adjacent dysplasia and 11 cases of active ulcerative colitis. The data indicate that PADI2 is the dominantly expressed PADI enzyme in colon mucosa and is upregulated during differentiation. PADI2 expression is low or absent in colorectal cancer. Frequently, this occurs already at the stage of low-grade dysplasia. Mucosal PADI2 expression is also low in ulcerative colitis. The expression level of PADI2 in tumor and adjacent mucosa correlates with differential survival: low levels associate with poor prognosis. (C) 2016 AACR.