IRF1 association with tumor immune microenvironment and use as a diagnostic biomarker for colorectal cancer recurrence

• Published in: Oncology letters Vol. 19; no. 3; pp. 1759 - 1770
• Main Authors: Wu, Yanfang, Zhang, Shuju, Yan, Jun
• Format: Journal Article
• Language: English
• Published: Greece Spandidos Publications 01.03.2020; Spandidos Publications UK Ltd; D.A. Spandidos
• Subjects: Biological response modifiers; Cancer recurrence; Cancer therapies; Care and treatment; Clinical outcomes; Colorectal cancer; Datasets; Deoxyribonucleic acid; DNA; DNA methylation; Enzymes; Gene expression; Genes; Genomes; Genomics; Interferon; Interleukins; Kinases; Lymphocytes; Macrophages; Medical diagnosis; Messenger RNA; Metastasis; Methylation; Mutation; Oncology; Protein binding; Protein-protein interactions; Proteins; Recurrence (Disease); RNA; Statistical analysis; Survival analysis; T cells; Time; Tumors; China; DNA methylation; colorectal cancer recurrence; tumor microenvironment; interferon regulatory factor 1; M1 macrophages; activated memory CD4+ T cells
• ISSN: 1792-1074; 1792-1082
• DOI: 10.3892/ol.2020.11289

Colorectal cancer (CRC) is considered to be one of the most lethal cancer types globally, and its recurrence is a major treatment challenge. Identifying the factors involved when determining the risk of CRC recurrence is required to improve personalized therapy for patients with CRC. Based on the GSE39582 dataset, the present study demonstrated that a higher ratio of M1 macrophages and activated memory CD4 T cells indicated a better recurrence-free survival (RFS) time for CRC, using CIBERSORT and Pearson's correlation analysis. Through weighted correlation network analysis (WGCNA), an immune-associated module was identified that was significantly positively correlated with the ratio of M1 macrophages and activated memory CD4 T cells. In this module, using WGCNA and a protein-protein interaction network, interferon regulatory factor 1 (IRF1), chemokine ligand 5, ubiquitin/ISG15-conjugating enzyme E2 L6, guanylate binding protein 1 and interleukin 2 receptor subunit beta were identified as hub genes. Among these genes, univariate Cox and multivariate Cox analysis revealed that IRF1 may be a potential diagnostic biomarker for RFS in patients with CRC. This was further validated using The Cancer Genome Atlas data. Gene set enrichment analysis demonstrated that IRF1 influenced the genes and pathways that are associated with immune cell recruitment and activation. Additionally, the DNA methylation of cg27587780 and cg15375424 CpG sites in the IRF1 gene region was indicated to be negatively correlated with IRF1 mRNA expression and positively correlated with the recurrence of CRC. Collectively, the results of the present study demonstrated that IRF1 may be a potential diagnostic biomarker for RFS in patients with CRC.