IRF1-mediated immune cell infiltration is associated with metastasis in colon adenocarcinoma

Abstract

Background: Evidence suggests that metastasis is chiefly responsible for the poor prognosis of colon adenocarcinoma (COAD). The tumor microenvironment plays a vital role in regulating this biological process. However, the mechanisms involved remain unclear. The aim of this study was to identify crucial metastasis-related biomarkers in the tumor microenvironment and investigate its association with tumor-infiltrating immune cells. Methods: We obtained gene expression profiles and clinical information from The Cancer Genome Atlas database. According to the “Estimation of STromal and Immune cells in MAlignant Tumor tissue using Expression data” algorithm, each sample generated the immune and stromal scores. Following correlation analysis, the metastasis-related gene was identified in The Cancer Genome Atlas database and validated in the GSE40967 dataset from Gene Expression Omnibus. The correlation between metastasis-related gene and infiltrating immune cells was assessed using the Tumor IMmune Estimation Resource database. Results: The analysis included 332 patients; the metastatic COAD samples showed a low immune score. Correlation analysis results showed that interferon regulatory factor 1 (IRF1) was associated with tumor stage, lymph node metastasis, and distant metastasis. Furthermore, significant associations between IRF1 and CD8+ T cells, T cell (general), dendritic cells, T-helper 1 cells, and T cell exhaustion were demonstrated by Spearmans correlation coefficients and P values. Conclusions: The present findings suggest that IRF1 is associated with metastasis and the degree of immune infiltration of CD8+ T cells (general), dendritic cells, T-helper 1 cells, and T cell exhaustion in COAD. These results may provide information for immunotherapy in colon cancer.

C1q+ macrophages: passengers or drivers of cancer progression

“…In lung cancer a similar increase in CXCL-10 was described in C1Q+ TAM, in association with an enrichment of the transcription factors IRF1, IRF7 and STAT1 16 . IRF1 correlates with STAT1, HLA-DR, PD-1 and LAG-3 in metastases of colorectal cancer 18 . Moreover, in ccRCC tumors, C1q+ cell density correlated with expression of inhibitory receptors PD-1 and LAG3 at the CD8+ T cells surface 5 , and these C1Q+ macrophages express additional immune checkpoint ligands, such as PD-L1 and PDL-2 4,5 .…”

Six Genes Associated with Lymphatic Metastasis in Colon Adenocarcinoma Linked to Prognostic Value and Tumor Immune Cell Infiltration

“…Further investigation revealed that IPS scores of patients also differed between different groups of six-gene risk scores. Similar studies have selected IRF1 as a biomarker to explore its relationship with immune cell infiltration and COAD metastasis [ 44 ]. IRF1 is associated with metastasis and the degree of immune infiltration of CD8 + T cells (general), dendritic cells, T-helper 1 cells, and T cell exhaustion in COAD, further demonstrating that immune cell infiltration can affect COAD lymphatic metastasis.…”

Development and validation of a survival prediction model for 113,239 patients with colon cancer: a retrospective cohort study

“…T stage refers to the depth of the tumor invasion, affecting the prognosis of CC patients. Lymphatic vessels of the colonic wall arise from the submucosal layer, and if the tumor infiltration reaches the submucosal layer, lymph node metastasis may occur (24)(25)(26)(27). The deeper the invasion, the higher the probability of lymph node metastasis and the poorer the prognosis.…”