Metabolomic Evidence for a Field Effect in Histologically Normal and Metaplastic Tissues in Patients with Esophageal Adenocarcinoma.

Metabolomic Evidence for a Field Effect in Histologically Normal and Metaplastic Tissues in Patients with Esophageal Adenocarcinoma.
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DOI:
10.1016/j.neo.2016.11.003
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发表时间:
2017-03
期刊:
Neoplasia (New York, N.Y.)
影响因子:
--
通讯作者:
Günther UL
Günther UL
中科院分区:
其他
文献类型:
--
作者:
Reed MAC;Singhal R;Ludwig C;Carrigan JB;Ward DG;Taniere P;Alderson D;Günther UL

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Barrett食管(BO)患者发生食管腺癌(EAC)的风险增加。然而,大多数巴雷特的患者不会发展为EAC,并且需要可以识别最危险的标记物。本研究旨在了解是否存在与EAC发展相关的代谢特征。为此,使用1H核磁共振分析了EAC、BO和正常食管患者的组织提取物。在可能的情况下,对EAC和BO患者的相邻组织学正常组织进行采样。该研究包括46例EAC患者,7例BO患者和68例正常外观的消化不良症状接受内镜检查的对照组。在癌症队列中,9名患者在适合活检的癌症附近患有非肿瘤性巴雷特氏病。在EAC患者中,可以区分组织学正常、BO和EAC组织[受试者工作曲线下面积(AUROC)1.00、0.86和0.91]以及存在和不存在EAC的组织学良性BO(AUROC 0.79)。在这两种情况下,样本数量限制了模型的功效。EAC近端组织学正常组织与对照组组织学正常组织的比较(AUROC 1.00)表明,可能在明显EAC之前发生强场效应,因此可用于识别发生EAC的高风险患者。该模型具有很好的敏感性和特异性,可区分EAC患者和健康对照组的组织学正常鳞状食管粘膜,其中8种代谢产物发生了非常显著的改变。如果分子标记可以检测到随后产生肿瘤的组织,则这可能具有潜在的诊断价值。
Patients with Barrett's esophagus (BO) are at increased risk of developing esophageal adenocarcinoma (EAC). Most Barrett's patients, however, do not develop EAC, and there is a need for markers that can identify those most at risk. This study aimed to see if a metabolic signature associated with the development of EAC existed. For this, tissue extracts from patients with EAC, BO, and normal esophagus were analyzed using 1H nuclear magnetic resonance. Where possible, adjacent histologically normal tissues were sampled in those with EAC and BO. The study included 46 patients with EAC, 7 patients with BO, and 68 controls who underwent endoscopy for dyspeptic symptoms with normal appearances. Within the cancer cohort, 9 patients had nonneoplastic Barrett's adjacent to the cancer suitable for biopsy. It was possible to distinguish between histologically normal, BO, and EAC tissue in EAC patients [area under the receiver operator curve (AUROC) 1.00, 0.86, and 0.91] and between histologically benign BO in the presence and absence of EAC (AUROC 0.79). In both these cases, sample numbers limited the power of the models. Comparison of histologically normal tissue proximal to EAC versus that from controls (AUROC 1.00) suggests a strong field effect which may develop prior to overt EAC and hence be useful for identifying patients at high risk of developing EAC. Excellent sensitivity and specificity were found for this model to distinguish histologically normal squamous esophageal mucosa in EAC patients and healthy controls, with 8 metabolites being very significantly altered. This may have potential diagnostic value if a molecular signature can detect tissue from which neoplasms subsequently arise.
DOI: 10.7150/jca.6990
发表时间: 2013
期刊: Journal of Cancer
影响因子: 3.9
作者:
Fasanella KE;Bista RK;Staton K;Rizvi S;Uttam S;Zhao C;Sepulveda A;Brand RE;McGrath K;Liu Y
通讯作者: Liu Y