Molecular profiling of downregulated genes in T-DM۱ resistance: insights from OE-۱۹ esophageal cancer cells

Introduction: Esophageal cancer is a challenging disease because it is aggressive and has limitedtreatment options. T-DM۱, a medication targeting HER۲-positive cancer cells, has shown promise inimproving patient outcomes. However, drug resistance is still a significant obstacle [۱, ۲]. To developeffective therapeutic strategies, it is crucial to understand the molecular mechanisms that cause T-DM۱resistance.Methods: In this study, we aimed to identify the essential regulatory genes and pathways involved inthe progression of TDM۱ resistance in OE-۱۹ EC cells. We extracted expression datasets from GEOomnibus, analyzed gene interactions, analyzed the reconstructed protein-protein interaction network,and performed enrichment analysis of the hub genesResults: We identified six hub genes (ALDH۱A۱, SLPI, CEBPA, RAC۲, PIWIL۱, and PRODH) as thekey downregulated genes (Figure ۱) that are mostly involved in the synthesis of GDP-mannose,Fructose Catabolism, Fructose Metabolism, and ROS And RNS Production In Phagocytes. Theheterocycle catabolic process, gamma-aminobutyric acid metabolic process, and intrinsic apoptoticsignaling pathway in response to oxidative stress were shown to be significantly enriched in GOanalysis. The most prominent cellular components were the chromatoid body, NADPH oxidasecomplex, and mitochondrial membrane. Retinal dehydrogenase, aldehyde dehydrogenase (NAD+), andoxidoreductase activity were significantly enriched in molecular functions.Conclusion: This study thoroughly examines the molecular landscape behind TDM-۱ resistance inesophageal cancer cell lines. The discovered hub genes and pathways offer prospective treatment targetsand shed light on the complicated resistance mechanisms at work. Further experimental validation ofthese findings is required for future clinical application.

کلیدواژه ها:

Biological networks ، Differentially expressed genes ، Esophageal cancer ، Protein-protein interactions ، Therapeutic target