NOVEL MICRORNA PROFILING OF ESOPHAGEAL ADENOCARCINOMA USING TRANSCRIPTOME ANALYSIS
Ryan Corlett*, Kalyana Nandipati
Surgery, Creighton University School of Medicine, Omaha, NE
Esophageal adenocarcinoma is a cancer that arises through a series of metaplastic changes to the esophageal mucosa and typically carries a poor prognosis. Esophageal adenocarcinoma is a growing cause for concern throughout the world, with incidence rising sharply over the last three decades. In Western countries the rise in esophageal adenocarcinoma has been particularly dramatic, with incidence surpassing that of esophageal squamous cell carcinoma. Many physiologic risk factors have been described for esophageal adenocarcinoma including gastroesophageal reflux disease (GERD), Barrett's esophagus, obesity, and tobacco smoking. The molecular pathophysiology of esophageal adenocarcinoma has yet to be fully characterized and could provide valuable insight into the diagnosis and treatment of this disease.
Gene expression is regulated by a variety of regulatory molecules including microRNAs (miRNAs). miRNAs are small, conserved ribonucleic acid molecules that regulate cellular processes. When dysregulated, miRNAs may contribute to oncogenesis and have been described to influence the progression of many human cancers. The exact profile of miRNAs associated with the pathogenesis of esophageal adenocarcinoma is unknown, though some candidate miRNAs have been reported in the literature. To identify the unique miRNA profile associated with esophageal adenocarcinoma, we compared esophageal adenocarcinoma tissue to adjacent healthy tissues through bulk RNA sequencing analysis and validated our findings using real-time polymerase chain reaction. We then conducted Ingenuity Pathway Analysis (IPA) to identify miRNA-gene relationships. We further utilized Causal Network Analysis and Upstream Regulator Analysis to identify miRNA-gene relationships that are not readily observed using traditional methods of sequencing analysis.
Our analysis identified 37 aberrantly expressed miRNAs in esophageal adenocarcinoma compared to control tissue, including 34 miRNAs that have not been previously reported in EAC. Seven miRNAs were found to be associated with activated networks in esophageal adenocarcinoma tissues and 30 miRNAs were associated with inhibited networks.
The miRNA-gene relationships that we identified provide novel insights into potentially oncogenic molecular pathways associated with the development of esophageal adenocarcinoma and may be used as future biomarkers for treatment strategies.
miRNA-Gene Network 1 of 4: microRNAs identified in activated networks through Causal Network analysis (esophageal adenocarcinoma vs. healthy adjacent tissue). Red circles: upregulated genes, green circles: downregulated genes, blue squares: microRNA's, dotted line: predicted gene-gene interaction, solid line: predicted miRNA interaction with gene.
Back to 2023 Abstracts