Identification of immune and ferroptosis-related gene cysteine dioxygenase type 1 (CDO1) as a prognostic biomarker in colorectal cancer, relating to immunotherapy response distinction

BACKGROUND: Colorectal cancer (CRC) is the third most common cause of cancer deaths worldwide, and has a poor prognosis in advanced stages. Whereas there are limited effective biomarkers of CRC. Herein, we aimed to explore the potential prognostic value of immune and ferroptosis-related genes (IFRGs). METHODS: CRC-related data were extracted from the Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. Kaplan-Meier, receiver operating characteristic (ROC), and multivariate Cox regression analyses were used to test the prognostic value of IFRGs. The immune cell infiltration and immunotherapy response predictive analyses were also conducted. The level of cysteine dioxygenase type 1 (CDO1) mRNA and protein expression in CRC and normal tissues was examined using quantitative reverse transcription polymerase chain reaction (qRT-PCR) and Western blotting analysis, respectively. RESULTS: Thirty-eight IFRGs were obtained through differentially expressed gene analysis and cross-analysis. Of them, CDO1 mRNA and protein expression levels were significantly reduced in CRC tissues compared to normal tissues. CDO1 remained as an independent prognostic biomarker after multivariate Cox regression. Additionally, CDO1 hypermethylation was associated with poorer prognosis of CRC patients. CRC patients with differential CDO1 expression or methylation status both showed significantly distinct immune cell infiltration and immunotherapy responses. CONCLUSIONS: Our study revealed CDO1 as an IFRG with a prognostic role in CRC. It may provide a rationale for developing novel treatment strategies, such as demethylating agents or combination immunotherapy protocols, for CRC.