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Decoding Common Genetic Alterations Between Barrett's Esophagus and Esophageal Adenocarcinoma: A Bioinformatics Analysis Publisher



Jalali P1 ; Yaghoobi A1 ; Rezaee M1 ; Zabihi MR2 ; Piroozkhah M1 ; Aliyari S3 ; Salehi Z4, 5
Authors
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Authors Affiliations
  1. 1. Basic and Molecular Epidemiology of Gastrointestinal Disorders Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran
  2. 2. Department of Immunology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
  3. 3. Division of Applied Bioinformatics, German Cancer Research Center DKFZ Heidelberg, Iran
  4. 4. Hematology, Oncology and Stem Cell Transplantation Research Center, Tehran University of Medical Sciences, Tehran, Iran
  5. 5. Research Institute for Oncology, Hematology and Cell Therapy, Tehran University of Medical Sciences, Tehran, Iran

Source: Heliyon Published:2024


Abstract

Background: Esophageal adenocarcinoma (EAC) is a common cancer with a poor prognosis in advanced stages. Therefore, early EAC diagnosis and treatment have gained attention in recent decades. It has been found that various pathological changes, particularly Barrett's Esophagus (BE), can occur in the esophageal tissue before the development of EAC. In this study, we aimed to identify the molecular contributor in BE to EAC progression by detecting the essential regulatory genes that are differentially expressed in both BE and EAC. Materials and methods: We conducted a comprehensive bioinformatics analysis to detect BE and EAC-associated genes. The common differentially expressed genes (DEGs) and common single nucleotide polymorphisms (SNPs) were detected using the GEO and DisGeNET databases, respectively. Then, hub genes and the top modules within the protein-protein interaction network were identified. Moreover, the co-expression network of the top module by the HIPPIE database was constructed. Additionally, the gene regulatory network was constructed based on miRNAs and circRNAs. Lastly, we inspected the DGIdb database for possible interacted drugs. Results: Our microarray dataset analysis identified 92 common DEGs between BE and EAC with significant enrichment in skin and epidermis development genes. The study also identified 22 common SNPs between BE and EAC. The top module of PPI network analysis included SCEL, KRT6A, SPRR1A, SPRR1B, SPRR3, PPL, SPRR2B, EVPL, and CSTA. We constructed a ceRNA network involving three specific mRNAs, 23 miRNAs, and 101 selected circRNAs. According to the results from the DGIdb database, TD101 was found to interact with the KRT6A gene. Conclusion: The present study provides novel potential candidate genes that may be involved in the molecular association between Esophageal adenocarcinoma and Barrett's Esophagus, resulting in developing the diagnostic tools and therapeutic targets to prevent progression of BE to EAC. © 2024 The Authors
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