SIGLEC1 has the potential to be an immune-related prognostic indicator in colon adenocarcinoma: a study based on transcriptomic data and Mendelian randomization analysis

Abstract

Abstract Background Colonic adenocarcinoma (COAD) is the most common pathological type of colon cancer. Tumor microenvironment (TME) plays an important role in the occurrence and development of COAD. There are currently no specific studies indicating the mechanism of action of TME in COPD patients. Methods The percentage of tumor-infiltrating immune cells (TIC) in 512 COAD cases from The Cancer Genome Atlas (TCGA) database was calculated using CIBERSORT and ESTIMATE. Weighted gene coexpression network analysis (WGCNA) was performed to find modules of differentially expressed genes (DEGs) with high correlations followed by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses to determine the function of distant metastasis (M)-stage-related modules. Pathway enrichment analysis, protein–protein interaction (PPI) network, Cox regression analysis, and Kaplan–Meier survival analysis were performed on DEGs to select the most critical genes. The correlation between SIGLEC1 expression in COAD and TME status and between immune checkpoints and SIGLEC1 was examined using gene set enrichment analysis (GSEA) and Pearson correlation coefficients. Results A WGCNA screen was performed to obtain 12,342 DEGs and 209 key genes associated with M stage between tumor and normal samples. GO and KEGG analysis revealed that the DEGs primarily engaged in pathways such as Th1 and Th2 cell differentiation and cell adhesion molecules. SIGELEC1 gene was identified by univariate Cox regression, PPI network construction, and survival analysis. GSEA showed that the genes in the high-expression SIGLEC1 group were mainly enriched in immune-related activities. In the low-expression SIGLEC1 group, the genes were enriched in MYC targets. CIBERSORT analysis of the proportion of TICs showed that SIGLEC1 was positively correlated with macrophages (M0, M2), T-cell CD8 and immune checkpoint-related genes, suggesting that SIGLEC1 may be responsible for maintaining the immune dominance of TME. Immunohistochemical and prognostic analysis showed that the group with higher SIGLEC1 expression had more severe lesions and a worse prognosis than the group with lower SIGLEC1 expression. Conclusions SIGLEC1 gene is a distant metastasis-related gene that affects the survival prognosis of COAD patients and provides additional insight into the treatment of COAD.

Keywords

• Colon cancer
• Tumor microenvironment (TME)
• Distant metastasis
• ESTIMATE
• Algorithm
• WGCNA analysis