Genomic similarity between gastroesophageal junction and esophageal Barrett's adenocarcinomas.
Genomic similarity between gastroesophageal junction and esophageal Barrett's adenocarcinomas.
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DOI：
10.18632/oncotarget.10253
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发表时间：
2016-08-23
期刊：
影响因子：
--
通讯作者：
Beer DG
中科院分区：
文献类型：
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作者：
Ferrer-Torres D;Nancarrow DJ;Kuick R;Thomas DG;Nadal E;Lin J;Chang AC;Reddy RM;Orringer MB;Taylor JM;Wang TD;Beer DG
目前食管腺癌（EAC）的高死亡率反映了其在晚期的频繁表现。最近利用荧光肽的努力已经确定了用于内窥镜检测早期巴雷特衍生EAC的过表达细胞表面靶标。不幸的是，30%的EAC患者存在胃食管连接部腺癌（GEJAC），缺乏癌前Barrett化生，限制了这种早期检测策略。我们比较了从胃食管交界处以上收集的52个EAC（管状EAC; tEAC）与70个GEJAC，8个正常食管和5个正常胃粘膜样本的mRNA谱。我们还分析了我们以前发表的这些肿瘤的大队列的全外显子组测序数据。主成分分析、层次聚类和基于生存率的分析表明，GEJAC和tEAC高度相似，表达和突变谱仅存在适度差异。组合表达组群允许鉴定在GEJAC和tEAC中过表达的49个编码细胞表面靶标的基因。我们证实，这些候选人（CDH 11，ICAM 1和CLDN 3）在肿瘤中过表达相比，正常食管，正常胃和非发育异常的巴雷特，并定位于肿瘤细胞的表面。tEAC和GEJAC肿瘤的分子分析表明存在广泛的相似性和相关的分子过程。鉴定的编码在巴雷特衍生的EAC和那些没有巴雷特化生的EAC中过表达的细胞表面蛋白的基因将允许同时检测策略。
The current high mortality rate of esophageal adenocarcinoma (EAC) reflects frequent presentation at an advanced stage. Recent efforts utilizing fluorescent peptides have identified overexpressed cell surface targets for endoscopic detection of early stage Barrett's-derived EAC. Unfortunately, 30% of EAC patients present with gastroesophageal junction adenocarcinomas (GEJAC) and lack premalignant Barrett's metaplasia, limiting this early detection strategy. We compared mRNA profiles from 52 EACs (tubular EAC; tEAC) collected above the gastroesophageal junction with 70 GEJACs, 8 normal esophageal and 5 normal gastric mucosa samples. We also analyzed our previously published whole-exome sequencing data in a large cohort of these tumors. Principal component analysis, hierarchical clustering and survival-based analyses demonstrated that GEJAC and tEAC were highly similar, with only modest differences in expression and mutation profiles. The combined expression cohort allowed identification of 49 genes coding cell surface targets overexpressed in both GEJAC and tEAC. We confirmed that three of these candidates (CDH11, ICAM1 and CLDN3) were overexpressed in tumors when compared to normal esophagus, normal gastric and non-dysplastic Barrett's, and localized to the surface of tumor cells. Molecular profiling of tEAC and GEJAC tumors indicated extensive similarity and related molecular processes. Identified genes that encode cell surface proteins overexpressed in both Barrett's-derived EAC and those that arise without Barrett's metaplasia will allow simultaneous detection strategies.