Pan-cancer analysis reveals HMOX1 as a cancer prognosis and immune infiltration-related biomarker

HMOX1 has gained increasing recognition across multiple malignancies; however, its precise oncogenic or tumor-suppressive roles remain incompletely defined. In this study, we comprehensively investigated HMOX1 across diverse tumor types utilizing the cancer genome atlas (TCGA). We further integrated data from multiple bioinformatics platforms, including TIMER2, UALCAN, GEPIA2, cBioPortal, R, GSCA, and LinkedOmics. Western blotting and quantitative real-time PCR (qRT-PCR) confirmed differential HMOX1 expression between normal renal epithelial cells and KIRC cells. Functional assays <i>in vitro</i> and <i>in vivo</i> demonstrated that HMOX1 regulates proliferation, migration, and cell-cycle progression in 786-O and Caki-1 cells. Pan-cancer analyses revealed that HMOX1 is aberrantly expressed across multiple malignancies with significant associations with the tumor stage. Survival analyses indicated that elevated HMOX1 expression predicted poor overall survival (OS) in LGG (<i>P</i> = 0.025) but favorable OS and disease-free survival (DFS) in KIRC (OS: <i>P</i> = 0.00062; DFS: <i>P</i> = 9 × 10^-4). Moreover, mutations were the predominant genetic alteration affecting HMOX1, while promoter methylation was broadly reduced across cancers. HMOX1 expression positively correlated with immune infiltration by CD8⁺ T cells (KIRC: Spearman <i>ρ</i> = 0.26, FDR = 2.56 × 10^-8) and macrophages (KIRC: Spearman <i>ρ</i> = 0.32, FDR = 2.77 × 10^-13). Gene Ontology and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses in KIRC implicated HMOX1 in the chemokine and NF-κB signaling pathways. Both <i>in vitro</i> and <i>in vivo</i> experiments demonstrated that HMOX1 knockdown accelerates cell-cycle progression and enhances proliferation and migration in 786-O and Caki-1 cells. Collectively, our findings establish HMOX1 as a promising prognostic biomarker and potential immunotherapeutic target across multiple cancers.