使用纳米级核架构图谱预测巴雷特食管的肿瘤进展：一项初步研究。
Prediction of neoplastic progression in Barrett's esophagus using nanoscale nuclear architecture mapping: a pilot study.
机构信息
Department of Gastroenterology and Hepatology, Cleveland Clinic, Cleveland, Ohio, USA.
Department of Pathology, Cleveland Clinic, Cleveland, Ohio, USA.
出版信息
Gastrointest Endosc. 2022 Jun;95(6):1239-1246. doi: 10.1016/j.gie.2022.01.007. Epub 2022 Jan 20.
BACKGROUND AND AIMS
Nanoscale nuclear architecture mapping (nanoNAM), an optical coherence tomography-derived approach, is capable of detecting with nanoscale sensitivity structural alterations in the chromatin of epithelial cell nuclei at risk for malignant transformation. Because these alterations predate the development of dysplasia, we aimed to use nanoNAM to identify patients with Barrett's esophagus (BE) who might progress to high-grade dysplasia (HGD) or esophageal adenocarcinoma (EAC).
METHODS
This is a nested case-control study of 46 BE patients, of which 21 progressed to HGD/EAC over 3.7 ± 2.37 years (cases/progressors) and 25 patients who did not progress over 6.3 ± 3.1 years (control subjects/nonprogressors). The archived formalin-fixed paraffin-embedded tissue blocks collected as part of standard clinical care at the index endoscopy were used. nanoNAM imaging was performed on a 5-μm formalin-fixed paraffin-embedded section, and each nucleus was mapped to a 3-dimensional (3D) depth-resolved optical path difference (drOPD) nuclear representation, quantifying nanoscale-sensitive alterations in the 3D nuclear architecture of the cell. Using 3D-drOPD representation of each nucleus, we computed 12 patient-level nanoNAM features summarizing the alterations in intrinsic nuclear architecture. A risk prediction model was built incorporating nanoNAM features and clinical features.
RESULTS
A statistically significant differential shift was observed in the drOPD cumulative distributions between progressors and nonprogressors. Of the 12 nanoNAM features, 6 (mean-maximum, mean-mean, mean-median, entropy-median, entropy-entropy, entropy-skewness) showed a statistically significant difference between cases and control subjects. NanoNAM features based prediction model identified progression in independent validation sets, with an area under the receiver operating characteristic curve of 80.8% ± .35% (mean ± standard error), with an increase to 82.54% ± .46% when combined with length of the BE segment.
CONCLUSIONS
NanoNAM can serve as an adjunct to histopathologic evaluation of BE patients and aid in risk stratification.
背景与目的
纳米级核结构图谱（nanoNAM）是一种基于光学相干断层扫描的方法，能够以纳米级的灵敏度检测到处于恶性转化风险的上皮细胞核染色质的结构改变。由于这些改变发生在发育不良之前，我们旨在使用 nanoNAM 来识别可能进展为高级别发育不良（HGD）或食管腺癌（EAC）的 Barrett 食管（BE）患者。
方法
这是一项嵌套病例对照研究，纳入了 46 例 BE 患者，其中 21 例在 3.7 ± 2.37 年内进展为 HGD/EAC（病例/进展者），25 例在 6.3 ± 3.1 年内未进展（对照/非进展者）。使用的是在索引内镜检查时作为标准临床护理收集的存档福尔马林固定石蜡包埋组织块。在 5μm 福尔马林固定石蜡包埋切片上进行 nanoNAM 成像，将每个细胞核映射到三维（3D）深度分辨光程差（drOPD）核表示中，定量测量细胞 3D 核结构中纳米级敏感的改变。使用每个细胞核的 3D-drOPD 表示，我们计算了 12 个患者级别的 nanoNAM 特征，总结了固有核结构的改变。构建了一个包含 nanoNAM 特征和临床特征的风险预测模型。
结果
在进展者和非进展者之间，drOPD 累积分布观察到统计学上显著的差异偏移。在 12 个 nanoNAM 特征中，有 6 个（均值-最大值、均值-均值、均值-中位数、熵-中位数、熵-熵、熵-偏度）在病例和对照之间表现出统计学上的显著差异。基于 nanoNAM 特征的预测模型在独立验证集中识别出进展，受试者工作特征曲线下面积为 80.8% ±.35%（均值 ± 标准误差），当与 BE 段长度结合时增加到 82.54% ±.46%。
结论
nanoNAM 可以作为 BE 患者组织病理学评估的辅助手段，并有助于风险分层。
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