Identifying Genetic Predispositions in Gastro-esophageal Disease Subtypes as Precursors to Esophageal Cancer

Abstract

Gastro-esophageal reflux disease (GRD) includes subtypes such as Barrett’s esophagus (BE), functional heartburn (FH), erosive reflux disease (ERD) and non-erosive reflux disease (NERD). These conditions are not only debilitating but can also lead to the development of esophageal cancer (ESCA). This progression is driven by chronic inflammation, changes in the cellular environment, and genetic factors. While previous research has demonstrated that all GRD subtypes could be predisposing factors to esophageal cancer, there is a significant lack of data on the perturbed gene pathways in GRD patients that are implicated in esophageal cancer and could play a role in its development. This research work therefore focused on elucidating gene signatures and notable biological processes in GRD sub-types, that could act as precursor factors to esophageal cancer using differential gene and pathway analysis, comparative condition-to-condition analysis and protein-protein interaction mapping. The results revealed a 47-gene signature including MUC17, AZGP1, TFF2 and CNN1, which is not only associated with all GRD subtypes but also implicated in esophageal cancer. Consistent with previous research, this study underscores the importance of MUC17, AZGP1, CLMP and CNN1 as key genes that drive the transition of GRD subtypes to esophageal cancer, offering potential pathways for improved diagnosis, monitoring, and treatment in GRD patients.