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

Abstract

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.

CX3CR1 Acts as a Protective Biomarker in the Tumor Microenvironment of Colorectal Cancer

“…P2RY13 is a G-protein-coupled receptor, and it was reported to be decreased upon epidermal growth factor (EGF)- and hypoxia-induced epithelial–mesenchymal transition (EMT) in breast cancer cells ( 57 , 58 ). Additionally, P2RY13 was also involved in the identification of M1 macrophages in CRC ( 59 ). However, multivariate Cox analysis showed that only T stage, N stage, and CX3CR1 were independent risk factors that could affect the prognosis of CRC.…”

Identification of Immune Cell Infiltration and Immune-Related Genes in the Tumor Microenvironment of Glioblastomas

“…These results were analyzed by long-rank test. The correlation between 24 hub genes and 22 immune cells was determined using Person's correlation analysis and CIBERSORT to reveal the relationship between hub genes and immune cells (17). Afterward, comprehensive correlation analysis between six selected survival-related hub genes and tumor-infiltrating immune cell signatures for GBM were performed using Tumor Immune Estimation Resource (TIMER 1.0, https://cistrome.shinyapps.…”

Development of a Novel Immune Infiltration-Related ceRNA Network and Prognostic Model for Sarcoma

“…The anti-tumorigenic role of interferon regulatory factor 1 (IRF1) has been reported in several types of cancer, by regulating genes related to PD-L1, DNA damage, apoptosis, and lymphocyte differentiation, also interacting multiple signaling pathways (Forero et al, 2019;Huang et al, 2019;Ohsugi et al, 2019;Wu et al, 2020). Moreover, IRF1 expression in tumor cells was also reported to be critical for the immune response to adoptive T cell therapy, as well as macrophage infiltration and memory CD4 + T cell activation (Wu et al, 2020). Zhang et al found that Manic Fringe (MFNG) was highly expressed in Claudin-low breast cancer and functioned as an oncogene by activating Notch signaling, thereby promoting tumor cell migration, tumorsphere formation, and epithelial-to-mesenchymal transition (EMT) (Zhang et al, 2015).…”