NOX4 has the potential to be a biomarker associated with colon cancer ferroptosis and immune infiltration based on bioinformatics analysis.

ABSTRACT

Background: Colon cancer (CC) is a common tumor, but its pathogenesis is still not well understood. Competitive endogenous RNA (ceRNA) theory, ferroptosis and tumor immune infiltration may be the mechanisms of the development of cancer. The purpose of the study is to seek genes connected with both immunity and ferroptosis, and provide important molecular basis for early noninvasive diagnosis and immunotherapy of CC. Methods: We extracted messenger RNA (mRNA), microRNA (miRNA), and long noncoding RNA (lncRNA) data of CC from The Cancer Genome Atlas database (TCGA), identified the differentially expressed mRNA (DEmRNA), miRNA (DEmiRNA) and lncRNA (DElncRNA), then constructed a ceRNA network. Venn overlap analysis was used to identify genes associated with immunity and ferroptosis in ceRNA network. The expression and prognosis of target genes were analyzed via Gene Expression Profiling Interactive Analysis (GEPIA) and PrognoScan database, and we analysed the related functions and signaling pathways of target genes by enrichment analysis. The correlation between target genes and tumor immune infiltrating was explored by CIBERSORT and spearman correlation analysis. Finally, the expression of target genes was detected via quantitative reverse transcription-PCR (qRT-PCR) in CC and normal colon tissues. Results: Results showed that there were 4 DElncRNA, 4 DEmiRNA and 126 DEmRNA in ceRNA network. NADPH oxidase 4 protein (NOX4) was a DEmRNA associated with immunity and ferroptosis in ceRNA network. NOX4 was highly expressed in CC and connected with unfavourable prognosis. NOX4 was obviously enriched in pathways connected with carcinogenesis and significantly correlated with six kinds of immune cells. Immune checkpoints and NOX4 spearman correlation analysis showed that the expression of NOX4 was positively related to programmed cell death protein 1 (PD-1)-PDCD1, programmed cell death-Ligand 1 (PD-L1)-CD274 and cytotoxic T-lymphocyte-associated protein 4 (CTLA4). Conclusions: To conclude, our study suggests that NOX4 is associated with both ferroptosis and tumor immunity, and might be a biomarker associated with the carcinogenesis, prognosis of CC and a potential target of CC immunotherapy.