Li Xianfeng, Wang Yan, Min Qingjie, Zhang Weimin, Teng Huajing, Li Chao, Zhang Kun, Shi Leisheng, Wang Bin, Zhan Qimin
Key laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Laboratory of Molecular Oncology, Peking University Cancer Hospital & Institute, Beijing 100142, China.
Department of Gastroenterology and Chongqing Key Laboratory of Digestive Malignancies, Daping Hospital, Army Medical University (Third Military Medical University), 10# Changjiang Branch Road, Yuzhong District, Chongqing 400042, People's Republic of China.
Comput Struct Biotechnol J. 2023 Jul 25;21:3841-3853. doi: 10.1016/j.csbj.2023.07.030. eCollection 2023.
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.
食管癌主要分为食管鳞状细胞癌（ESCC）和食管腺癌（EAC）。虽然已记录了与ESCC和EAC肿瘤发生相关的各种（表观）基因组改变，但这两种癌症亚型转录组的全面比较仍然缺乏。
我们从公开可用的来源收集了551个基因表达谱，包括正常组织、ESCC和EAC组织或细胞系。随后，我们进行了系统分析，以在多个水平上比较这些样本的转录组，包括基因表达、启动子活性、可变剪接（AS）、可变聚腺苷酸化（APA）和基因融合。
在正常组织、ESCC和EAC组织中差异表达的基因中鉴定出七种不同的聚类基因表达模式。这些模式在PI3K-Akt信号通路中富集，细胞外基质组织被激活，表皮发育受到抑制。值得注意的是，我们观察到在这些与肿瘤发生和免疫激活相关的共同途径和生物学过程中富集了额外的基因或独特的表达水平。除了差异表达的基因外，ESCC和EAC中lncRNA共表达网络均有富集，且与表皮发育抑制相关的启动子活性下调。这表明这两种癌症亚型之间存在共同特征。此外，ESCC和EAC中的差异AS和APA模式似乎部分影响了这些亚型中与细菌或病毒感染相关的宿主基因的表达。在ESCC和EAC之间未观察到基因融合，从而突出了这两种癌症亚型潜在的不同分子机制。
我们对ESCC和EAC转录组进行了全面比较，在多个水平上揭示了共同和不同的转录组特征。这些发现表明，ESCC和EAC在肿瘤发生过程中可能表现出共同和独特的机制。
