腸管の慢性炎症ならびに加齢による頻回の粘膜再上皮化は、腸管上皮細胞のDNAメチル化を異常誘発する因子であり、潰瘍性大腸炎(UC)合併大腸癌(CAC)に深く関与している。このように形成されるDNAメチル化異常は癌組織に加え、非癌部にも存在することが知られ(Field defect)、この現象は大腸腫瘍を合併する高危険群の絞り込みを可能にする新たな危険因子として期待される。今回の研究では、複数のDNAメチル化マーカーはField effectの特性を持ち、それらのマーカーパネルを用いたUC患者の直腸生検は、CAC合併患者の絞り込みに有用な検査方法として期待される結果であった。
Colitis-associated cancer (CAC) is higher among long-standing ulcerative colitis (UC) patients, such as that for whom surveillance colonoscopy is widely recommended. However, CAC is often difficult to detect endoscopically and histologically because of mucosal structure modifications by inflammation. Therefore, several molecular alterations may be promising as markers for identifying patients at high risk of developing CAC First, we investigated the feasibility of using the methylation status of several microRNAs, which have characteristic of both type C (methylated during carcinogenesis) and type A (methylated during aging) simultaneously as a promising biomarker in CAC. We next performed the analysis of these biomarkers from rectal biopsy specimen has robust predictive potential in identifying UC patients with CAC elsewhere in the colorectum. In addition, we confirmed the reproducibly by using a large cohort.
エピゲノムから考案した潰瘍性大腸炎癌化ハイリスク症例の診断方法の確立
2018RP0063
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