Promoter hypomethylation of SKI in autoimmune pancreatitis
Promoter hypomethylation of SKI in autoimmune pancreatitis
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DOI：
10.1016/j.prp.2018.03.005
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发表时间：
2018-04-01
影响因子：
2.8
通讯作者：
Ota, Hiroyoshi
中科院分区：
文献类型：
--
作者：
Kinugawa, Yasuhiro;Uehara, Takeshi;Ota, Hiroyoshi
自身免疫性胰腺炎（AIP）是一种典型的IgG4相关疾病，甲基化异常与AIP的关系尚未阐明。我们使用Illumine Infinium Human Methylation 450K BeadChip微阵列进行甲基化阵列分析，确定AIP中SKI可能存在显著的甲基化异常，并研究SKI与AIP临床病理特征的关系。采用SYBR绿色甲基化特异性定量PCR检测10例AIP、14例无ALP病史的胰腺导管腺癌（PDA）梗阻性胰腺炎区和9例正常胰腺（NP）组织中SKI甲基化率，并采用免疫组化检测SIG表达程度。AIP中SKI甲基化率显著低于PDA和NP。此外，尽管AIP和PDA之间没有显著差异，但AIP中SKI的免疫组化染色指数（SI）评分显著高于NP。SI评分与SIG甲基化率、血清IgG4浓度与SKI甲基化率呈显著负相关。血清IgG 4浓度与SI呈中度正相关。SKI被认为是一种癌基因，表明SKI低甲基化和致癌作用可能与MP有关。此外，血清IgG 4浓度与SKI甲基化水平之间的相关性表明SKI可能参与AIP的发病机制。然而，所罗门群岛政府的作用尚未明确阐明。进一步了解SKI的功能还需要进一步的研究。
The relationship between methylation abnormality and autoimmune pancreatitis (AIP) a representative IgG4related disease has not yet been elucidated. We identified SKI might have a significant methylation abnormality in AIP through methylation array analysis using the Illumine Infinium Human Methylation 450K BeadChip array, and investigated the relationship of SKI with AIP clinicopathological features. The methylation rate of SKI was assessed by quantitative SYBR green methylation-specific PCR, and the degree of SIG expression in tissue specimens was assessed by immtmohistochemistry in 10 AIP cases, 14 cases of obstructive pancreatitis area in pancreatic ductal adenocarcinoma (PDA) without a history of ALP, and 9 normal pancreas (NP) cases. The SKI methylation ratio was significantly lower in AIP than in PDA and NP. Additionally, the inununohistochemical staining-index (SI) score for SKI was significantly higher in AIP than NP, although there was no significant difference between AIP and PDA. There was a strong negative correlation between SI score and SIG methylation ratio, and between the serum concentrations of IgG4 and the SKI methylation ratio. There was a moderate positive correlation between the serum concentrations of IgG4 and SI. SKI is thought to be an oncogene indicating that SKI hypomethylation and carcinogenesis might be linked to MP. Furthermore, the correlation between serum concentrations of IgG4 and SKI methylation levels suggest SKI might be involved in the pathogenesis of AIP. However, the role of SIG has not been clearly elucidated. Further studies are needed to understand further the function of SKI.