具有独特分子亚型的食管腺癌具有特定的基因表达和突变模式。
Distinct esophageal adenocarcinoma molecular subtype has subtype-specific gene expression and mutation patterns.
机构信息
Department of Preventive Medicine, Joint National Laboratory for Antibody Drug Engineering, Institute of Biomedical Informatics ,School of Basic Medical Sciences, Henan University, Kaifeng, 475004, China.
Cell Signal Transduction Laboratory, Henan University, Kaifeng, 475004, China.
出版信息
BMC Genomics. 2018 Oct 24;19(1):769. doi: 10.1186/s12864-018-5165-0.
BACKGROUND
Esophageal carcinoma (EC), consists of two histological types, esophageal squamous carcinoma (ESCC) and esophageal adenocarcinoma (EAC). EAC accounted for 10% of EC for centuries; however, the prevalence of EAC has alarmingly risen 6 times and increased to about 50% of EC in recent 30 years in the western countries, while treatment options for EAC patients are still limited. Stratification of molecular subtypes by gene expression profiling methods had offered opportunities for targeted therapies. However, the molecular subtype in EAC has not been defined. Hence, Identification of EAC molecular subtypes is needed and will provide important insights for future new therapies.
RESULTS
We performed meta-analysis of gene expression profiling data on three independent EAC cohorts and showed that there are two common molecular subtypes in EAC. Each of the two EAC molecular subtypes has subtype specific expression patterns and mutation signatures. Genes which were over-expressed in subtype I EACs rather than subtype II EAC cases, were enriched in biological processes including epithelial cell differentiation, keratinocyte differentiation, and KEGG pathways including basal cell carcinoma. TP53 and CDKN2A are significantly mutated in both EAC subtypes. 24 genes including SMAD4 were found to be only significantly mutated in subtype I EAC cases, while 30 genes including ARID1A are only significantly mutated in subtype II EACs.
CONCLUSION
Two EAC molecular subtypes were defined and validated. This finding may offer new opportunities for targeted therapies.
背景
食管癌（EC）由两种组织学类型组成，食管鳞状细胞癌（ESCC）和食管腺癌（EAC）。EAC 占 EC 的比例在几个世纪以来一直为 10%；然而，在最近 30 年，西方国家 EAC 的患病率惊人地上升了 6 倍，增加到 EC 的约 50%，而 EAC 患者的治疗选择仍然有限。通过基因表达谱分析方法对分子亚型进行分层为靶向治疗提供了机会。然而，EAC 的分子亚型尚未确定。因此，需要确定 EAC 的分子亚型，这将为未来的新疗法提供重要的见解。
结果
我们对三个独立的 EAC 队列的基因表达谱数据进行了荟萃分析，结果表明 EAC 中有两种常见的分子亚型。这两种 EAC 分子亚型中的每一种都有特定的表达模式和突变特征。在 I 型 EAC 中过度表达的基因，而不是 II 型 EAC 病例，在生物学过程中富集，包括上皮细胞分化、角蛋白细胞分化，以及包括基底细胞癌在内的 KEGG 途径。TP53 和 CDKN2A 在两种 EAC 亚型中均发生显著突变。在 I 型 EAC 病例中发现 24 个基因（包括 SMAD4）仅显著突变，而在 II 型 EAC 中发现 30 个基因（包括 ARID1A）仅显著突变。
结论
定义并验证了两种 EAC 分子亚型。这一发现可能为靶向治疗提供新的机会。
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