Integrative bioinformatics analysis identifies HCCS as a prognostic and therapeutic biomarker in lung cancer

BackgroundLung cancer remains one of the leading causes of cancer-related mortality worldwide. Holocytochrome c synthase (HCCS), a mitochondrial enzyme involved in apoptosis and energy metabolism, has been implicated in tumorigenesis; however, its role in lung cancer is not well defined.AimThis study aimed to elucidate the prognostic and therapeutic potential of HCCS in lung cancer through integrative bioinformatics analyses.MethodsTranscriptomic, methylation, and clinical data from TCGA were analyzed using TNMplot, UALCAN, and TIMER2.0 to evaluate HCCS expression, promoter methylation, immune infiltration, and prognostic relevance in lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC). Meta-analysis of 18 independent cohorts from LUNG CANCER EXPLORER and four GEO datasets validated expression patterns, while Kaplan-Meier analysis assessed survival outcomes.ResultsHCCS was significantly upregulated in LUAD and LUSC and showed promoter hypermethylation in LUAD. Meta-analysis and external validation confirmed its overexpression. Patients with low HCCS expression exhibited poorer overall survival, suggesting a potential tumor-suppressive effect. HCCS expression positively correlated with immune cell infiltration and co-expressed genes enriched in mitochondrial and apoptotic pathways.ConclusionHCCS may serve as a prognostic and therapeutic biomarker in lung cancer, linking mitochondrial regulation, epigenetic modification, and immune interactions.