Identification of Molecular Subtypes and Potential Small-Molecule Drugs for Esophagus Cancer Treatment Based on m(6)A Regulators

基于m(6)A调节因子的食管癌分子亚型鉴定及潜在小分子药物治疗

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Abstract

BACKGROUND: Esophagus cancer (ESCA) is the sixth most frequent cancer in males, with 5-year overall survival of 15%-25%. RNA modifications function critically in cancer progression, and m(6)A regulators are associated with ESCA prognosis. This study further revealed correlations between m(6)A and ESCA development. METHODS: Univariate Cox regression analysis and consensus clustering were applied to determine molecular subtypes. Functional pathways and gene ontology terms were enriched by gene set enrichment analysis. Protein-protein interaction (PPI) analysis on differentially expressed genes (DEGs) was conducted for hub gene screening. Public drug databases were employed to study the interactions between hub genes and small molecules. RESULTS: Three molecular subtypes related to ESCA prognosis were determined. Based on multiple analyses among molecular subtypes, 146 DEGs were screened, and a PPT network of 15 hub genes was visualized. Finally, 8 potential small-molecule drugs (BMS-754807, gefitinib, neratinib, zuclopenthixol, puromycin, sulfasalazine, and imatinib) were identified for treating ESCA. CONCLUSIONS: This study applied a new approach to analyzing the relation between m(6)A and ESCA prognosis, providing a reference for exploring potential targets and drugs for ESCA treatment.

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