Kinugawa Yasuhiro, Uehara Takeshi, Matsuda Kazuyuki, Kobayashi Yukihiro, Nakajima Tomoyuki, Hamano Hideaki, Kawa Shigeyuki, Higuchi Kayoko, Hosaka Noriko, Shiozawa Satoshi, Ishigame Hiroki, Nakamura Toshitsugu, Maruyama Yasuhiro, Nakazawa Koh, Nakaguro Masato, Sano Kenji, Ota Hiroyoshi
Department of Laboratory Medicine, Shinshu University School of Medicine, Matsumoto, Japan.
Department of Laboratory Medicine, Shinshu University School of Medicine, Matsumoto, Japan.
Pathol Res Pract. 2018 Apr;214(4):492-497. doi: 10.1016/j.prp.2018.03.005. Epub 2018 Mar 6.
The relationship between methylation abnormality and autoimmune pancreatitis (AIP)-a representative IgG4-related disease-has not yet been elucidated. We identified SKI might have a significant methylation abnormality in AIP through methylation array analysis using the Illumina 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 SKI expression in tissue specimens was assessed by immunohistochemistry in 10 AIP cases, 14 cases of obstructive pancreatitis area in pancreatic ductal adenocarcinoma (PDA) without a history of AIP, and 9 normal pancreas (NP) cases. The SKI methylation ratio was significantly lower in AIP than in PDA and NP. Additionally, the immunohistochemical 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 SKI 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 AIP. 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 SKI has not been clearly elucidated. Further studies are needed to understand further the function of SKI.
甲基化异常与自身免疫性胰腺炎（AIP）——一种典型的IgG4相关性疾病——之间的关系尚未阐明。我们通过使用Illumina Infinium Human Methylation 450K BeadChip芯片进行甲基化阵列分析，发现SKI在AIP中可能存在显著的甲基化异常，并研究了SKI与AIP临床病理特征之间的关系。通过定量SYBR绿色甲基化特异性PCR评估SKI的甲基化率，通过免疫组织化学评估10例AIP病例、14例无AIP病史的胰腺导管腺癌（PDA）阻塞性胰腺炎区域病例和9例正常胰腺（NP）病例组织标本中SKI的表达程度。AIP中SKI的甲基化率显著低于PDA和NP。此外，AIP中SKI的免疫组织化学染色指数（SI）评分显著高于NP，尽管AIP与PDA之间无显著差异。SI评分与SKI甲基化率之间、IgG4血清浓度与SKI甲基化率之间存在强负相关。IgG4血清浓度与SI之间存在中度正相关。SKI被认为是一种癌基因，表明SKI低甲基化与致癌作用可能与AIP有关。此外，IgG4血清浓度与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，SKI的作用尚未明确阐明。需要进一步研究以深入了解SKI的功能。
