OBJECTIVES Intestinal neuronal dysplasia (IND) is a common malformation of the enteric nervous system. Diagnosis requires a full-thickness colonic specimen and an experienced pathologist, emphasizing the need for noninvasive analytical methods. Recently, the methylation level of the Sox10 promoter has been found to be critical for enteric nervous system development. However, whether it can be used for diagnostic purposes in IND is unclear. METHODS Blood and colon specimens were collected from 32 patients with IND, 60 patients with Hirschsprung disease (HD), and 60 controls. Sox10 promoter methylation in the blood and the Sox10 expression level in the colon were determined, and their correlation was analyzed. The diagnostic efficacy of blood Sox10 promoter methylation was analyzed by receiver operating characteristic curve. RESULTS The blood level of Sox10 promoter methylation at the 32nd locus was 100% (90%-100%; 95% confidence interval [CI], 92.29%-96.37%) in control, 90% (80%-90%; 95% CI, 82.84%-87.83%) in HD, and 60% (50%-80%; 95% CI, 57.12%-69.76%) in IND specimens. Sox10 promoter methylation in the peripheral blood was negatively correlated with Sox10 expression in the colon, which was low in control, moderate in HD, and high in IND specimens (r = -0.89). The area under the curve of Sox10 promoter methylation in the diagnosis of IND was 0.94 (95% CI, 0.874-1.000, P = 0.000), with a cutoff value of 85% (sensitivity, 90.6%; specificity, 95.0%). By applying a cutoff value of 65%, promoter methylation was more indicative of IND than HD. DISCUSSION The analysis of Sox10 promoter methylation in the peripheral blood can be used as a noninvasive method for IND diagnosis.

中文翻译：

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Sox10 启动子甲基化在外周血肠神经元发育不良诊断中的功效。

目的 肠神经元发育不良（IND）是肠神经系统的常见畸形。诊断需要全层结肠标本和经验丰富的病理学家，强调需要非侵入性分析方法。最近，人们发现 Sox10 启动子的甲基化水平对于肠神经系统的发育至关重要。然而，它是否可以用于 IND 中的诊断目的尚不清楚。方法 从 32 名 IND 患者、60 名先天性巨结肠 (HD) 患者和 60 名对照者中采集血液和结肠标本。测定血液中Sox10启动子甲基化和结肠中Sox10表达水平，并分析其相关性。通过受试者工作特征曲线分析血液Sox10启动子甲基化的诊断效能。结果 血液中 Sox10 启动子第 32 位点甲基化水平为 100%（90%-100%；95% 置信区间 [CI]，92.29%-96.37%），对照组为 90%（80%-90%；95%） HD 中的 CI，82.84%-87.83%），IND 样本中的 CI，60%（50%-80%；95% CI，57.12%-69.76%）。外周血中的 Sox10 启动子甲基化与结肠中的 Sox10 表达呈负相关，在对照中较低，在 HD 中中等，在 IND 标本中较高（r = -0.89）。Sox10启动子甲基化诊断IND的曲线下面积为0.94（95% CI，0.874-1.000，P = 0.000），截止值为85%（敏感性，90.6%；特异性，95.0%）。通过应用 65% 的截止值，启动子甲基化比 HD 更能指示 IND。讨论 外周血中Sox10启动子甲基化的分析可作为IND诊断的无创方法。