Pan-cancer analysis identifies JMJD6 as an oncogene and prognostic biomarker

Abstract JMJD6, a bifunctional epigenetic modulator within the Jumonji C family, has garnered increasing attention for its potential roles in tumorigenesis, yet its pan-cancer prognostic and mechanistic significance remain incompletely characterized. In this study, we performed a comprehensive pan-cancer analysis of JMJD6 using multi-omics data from public databases including TCGA, CPTAC, HPA, and GEPIA2. Our results revealed that JMJD6 is significantly overexpressed across cancers and positively correlated with advanced tumor stage and unfavorable patient survival outcomes. Mechanistically, JMJD6 overexpression was associated with promoter hypomethylation and showed close interactions with RNA modification regulators. Furthermore, JMJD6 expression correlated significantly with immune cell infiltration, elevated genomic instability (TMB, MSI, HRD), and differential sensitivity to targeted therapies such as EGFR inhibitors. Functional enrichment analysis underscored its involvement in spliceosome and chromatin remodeling pathways. Collectively, our findings establish JMJD6 as an influential oncogene and robust prognostic biomarker across cancer types, with implications for future therapeutic strategies targeting epigenetic and immune pathways.