NCOA4 serves as a potential prognostic biomarker and correlates with immune infiltrates in lung adenocarcinoma

Abstract Background The crucial role of Nuclear Receptor Coactivator 4 (NCOA4) in the mechanism underlying ferritinophagy-related tumor development remains incompletely understood, particularly in relation to lung adenocarcinoma (LUAD). Methods A retrospective study was conducted on a cohort of 65 patients with LUAD, wherein the expression of NCOA4 was assessed using immunohistochemistry (IHC). Kaplan-Meier survival analysis and univariate or multivariate analysis were performed to investigate the association between NCOA4 expression and clinical pathological features. Additionally, bioinformatics tools and enrichment analysis were employed to explore the expression profile of NCOA4 and its prognostic significance. Results The decreased expression of NCOA4 was significantly associated with a poor prognosis in patients with LUAD. Moreover, bioinformatics analysis revealed that increased NCOA4 expression was strongly correlated with improved overall survival (OS) in various tumor types, including LUAD. Enrichment analysis indicated that NCOA4 co-expressed genes such as ferritin heavy chain 1 (FTH1), androgen receptor (AR), ret tyrosine kinase (RET), Ferritin Light Chain (FTL), and Coiled-Coil Domain Containing 6 (CCDC6), which exhibited similar expression patterns to those observed in LUAD, were also linked to a favorable prognosis. Our results demonstrate a correlation between decreased expression of the ferritinophagy-related gene NCOA4 and the dual roles played by immune cell infiltration in LUAD. Furthermore, we have found a significant association between NCOA4 expression and most immune markers across different immune cell types in LUAD.These findings suggest that NCOA4 may serve as a potential prognostic biomarker and exhibit correlation with immune infiltrates in LUAD. Conclusion Our findings demonstrate a correlation between low expression of the ferritinophagy-related NCOA4 gene and dual roles played by immune cell infiltration in LUAD. NCOA4 holds promise as a novel marker for identifying potentially eligible patients for ferroptosis-inducing treatments or their combination with immunotherapy.