Comparative transcriptome characterization of esophageal squamous cell carcinoma and adenocarcinoma

Xianfeng Li; Yan Wang; Qingjie Min; Weimin Zhang; Huajing Teng; Chao Li; Kun Zhang; Leisheng Shi; Bin Wang; Qimin Zhan

doi:10.1016/j.csbj.2023.07.030

Comparative transcriptome characterization of esophageal squamous cell carcinoma and adenocarcinoma

Comput Struct Biotechnol J. 2023 Jul 25:21:3841-3853. doi: 10.1016/j.csbj.2023.07.030. eCollection 2023.

Authors

Xianfeng Li^{1

2

3

4}, Yan Wang¹, Qingjie Min¹, Weimin Zhang¹, Huajing Teng⁵, Chao Li⁶, Kun Zhang⁶, Leisheng Shi⁷, Bin Wang^{2

3

4}, Qimin Zhan¹

Affiliations

¹ Key laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Laboratory of Molecular Oncology, Peking University Cancer Hospital & Institute, Beijing 100142, China.
² 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.
³ Institute of Pathology and Southwest Cancer Center, Key Laboratory of Tumor Immunopathology of Ministry of Education of China, Southwest Hospital, Army Medical University (Third Military Medical University), Chongqing 400038, People's Republic of China.
⁴ Jinfeng Laboratory, Chongqing 401329, People's Republic of China.
⁵ Key laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Radiation Oncology, Peking University Cancer Hospital & Institute, Beijing 100142, China.
⁶ Institute of Genomic Medicine, Wenzhou Medical University, Wenzhou 325035, China.
⁷ Key Laboratory of Genomic and Precision Medicine, Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing 100101, China.

Abstract

Background: 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.

Methods: 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.

Results: 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.

Conclusions: 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.

Keywords: Esophageal adenocarcinoma; Esophageal squamous cell carcinoma; Transcriptome.