Abstract:
Introduction: Esophageal cancer is a challenging disease because it is aggressive and has limited treatment options. T-DM1, a medication targeting HER2-positive cancer cells, has shown promise in improving patient outcomes. However, drug resistance is still a significant obstacle. To develop effective therapeutic strategies, it is crucial to understand the molecular mechanisms that cause T-DM1 resistance.
Methods: In this study, we aimed to identify the essential regulatory genes and pathways involved in the progression of T-DM1 resistance in OE-19 EC cells. We extracted expression datasets from GEO omnibus, analyzed gene interactions, analyzed the reconstructed protein-protein interaction network, and performed enrichment analysis of the hub genes.
Results: We identified six hub genes (ALDH1A1, SLPI, CEBPA, RAC2, PIWIL1, and PRODH) as the key downregulated genes (Figure 1) that are mostly involved in the synthesis of GDP-mannose, Fructose Catabolism, Fructose Metabolism, and ROS And RNS Production In Phagocytes. The heterocycle catabolic process, gamma-aminobutyric acid metabolic process, and intrinsic apoptotic signaling pathway in response to oxidative stress were shown to be significantly enriched in GO analysis. The most prominent cellular components were the chromatoid body, NADPH oxidase complex, and mitochondrial membrane. Retinal dehydrogenase, aldehyde dehydrogenase (NAD+), and oxidoreductase activity were significantly enriched in molecular functions.
Conclusion: This study thoroughly examines the molecular landscape behind TDM-1 resistance in esophageal cancer cell lines. The discovered hub genes and pathways offer prospective treatment targets and shed light on the complicated resistance mechanisms at work. Further experimental validation of these findings is required for future clinical application.
Audience Take Away Notes:
- This study provides a molecular understanding of genes and pathways involved in T-DM1 resistance in esophageal cancer
- Our findings highlight the key genes and pathways in T-DM1 drug resistance in esophageal cancer, which could be considered as potential therapeutic targets to overcome cancer treatment challenges
