Expression and prognostic value of ferritinophagy-related NCOA4 gene in low-grade glioma: integration of bioinformatics and experimental validation.

Abstract

Background: Low-grade glioma (LGG) is a primary brain tumor with relatively low malignancy. NCOA4 is a key regulator of ferritinophagy-related processes and is involved in the occurrence and development of many cancers. However, the role of NCOA4 in LGG remains poorly understood.

Methods: This study comprehensively analyzed several mainstream bioinformatics databases to explore the expression, diagnostic efficacy, clinical pathological features, immune infiltration, prognostic value, and biological functions of NCOA4 in LGG. Immunohistochemistry experiments were conducted using LGG tissue samples collected from our hospital to validate the bioinformatics analysis results.

Results: NCOA4 expression was significantly elevated in LGG (p < 0.05), with an Area Under the Receiver Operating Characteristic Curve (AUC) of 0.973, suggesting it as a potential diagnostic marker. High NCOA4 expression was associated with younger age (21-40 years), lower malignancy (oligodendroglioma), and better prognosis (IDHmut-non-codel and IDHmut-codel subtypes) (all p < 0.05) in LGG. Kaplan-Meier survival curves from three databases showed that high NCOA4-expressing LGG patients had better prognosis (all p < 0.05). NCOA4 correlated weakly with B cells, CD8 + T cells, macrophages, and dendritic cells infiltration (all with correlation coefficients r < 0.3, and p < 0.05) in LGG. Multivariate Cox regression identified NCOA4, age, CD8 T cells, and macrophages as LGG independent prognostic factors (all p < 0.05). Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses indicated that NCOA4's primary function in LGG is related to autophagy processes (all p < 0.05).

Conclusion: Our findings suggest that NCOA4 could be a potential prognostic marker and therapeutic target in LGG.