食管癌主要分为食管鳞状细胞癌（ESCC）和食管腺癌（EAC）。尽管与ESCC和EAC肿瘤发展相关的各种（表观）基因组变异已有记录，但这两种癌症亚型间转录组的全面比较仍然缺乏。我们从公开来源收集了551个基因表达谱，包括正常、ESCC和EAC组织或细胞系。随后，我们对这些样本的转录组进行了系统分析，包括基因表达、启动子活性、可变剪接（AS）、可变多腺苷酸化（APA）和基因融合等多个层次的比较。 我们在正常、ESCC和EAC组织中的差异表达基因中鉴定出七种不同的基因表达模式群。这些模式在PI3K-Akt信号通路和细胞外基质结构活化方面具有丰富性，并且表现出抑制表皮发育的特征。值得注意的是，我们观察到这些共享通路和与肿瘤发展及免疫激活相关的生物过程中存在额外的基因或独特的表达水平富集。除了差异表达基因外，在ESCC和EAC中，伴随着表皮发育抑制的lncRNA共表达网络富集和启动子活性的下调也常见。这表明这两种癌症亚型之间存在共同特征。此外，在ESCC和EAC中的可变剪接和APA模式似乎部分影响与这些亚型中的细菌或病毒感染相关的宿主基因的表达。ESCC和EAC之间没有观察到基因融合，从而突显了这两种癌症亚型之间的不同分子机制。 我们对ESCC和EAC的转录组进行了全面比较，并发现了多个层次上共享和独特的转录组特征。这些发现表明ESCC和EAC可能在肿瘤发生机制中表现出共同和独特的特点。 © 2023 The Authors. 由Elsevier B.V.代表计算和结构生物技术研究网络出版。

Esophageal cancers are primarily categorized as esophageal squamous cell carcinoma (ESCC) and esophageal adenocarcinoma (EAC). While various (epi) genomic alterations associated with tumor development in ESCC and EAC have been documented, a comprehensive comparison of the transcriptomes in these two cancer subtypes remains lacking.We collected 551 gene expression profiles from publicly available sources, including normal, ESCC, and EAC tissues or cell lines. Subsequently, we conducted a systematic analysis to compare the transcriptomes of these samples at various levels, including gene expression, promoter activity, alternative splicing (AS), alternative polyadenylation (APA), and gene fusion.Seven distinct cluster gene expression patterns were identified among the differentially expressed genes in normal, ESCC, and EAC tissues. These patterns were enriched in the PI3K-Akt signaling pathway and the activation of extracellular matrix organization and exhibited repression of epidermal development. Notably, we observed additional genes or unique expression levels enriched in these shared pathways and biological processes related to tumor development and immune activation. In addition to the differentially expressed genes, there was an enrichment of lncRNA co-expression networks and downregulation of promoter activity associated with the repression of epidermal development in both ESCC and EAC. This indicates a common feature between these two cancer subtypes. Furthermore, differential AS and APA patterns in ESCC and EAC appear to partially affect the expression of host genes associated with bacterial or viral infections in these subtypes. No gene fusions were observed between ESCC and EAC, thus highlighting the distinct molecular mechanisms underlying these two cancer subtypes.We conducted a comprehensive comparison of ESCC and EAC transcriptomes and uncovered shared and distinct transcriptomic signatures at multiple levels. These findings suggest that ESCC and EAC may exhibit common and unique mechanisms involved in tumorigenesis.© 2023 The Authors. Published by Elsevier B.V. on behalf of Research Network of Computational and Structural Biotechnology.