Immune cell dynamics and prognostic role of M2 macrophages and LDOC1 in colon adenocarcinoma.

BACKGROUND: Colon adenocarcinoma (COAD) is influenced by the tumor microenvironment, including immune cell dynamics, particularly M2 macrophages. Understanding these dynamics can offer insights into tumor progression and potential therapies. METHODS: We analyzed TCGA COAD data to quantify immune infiltration using TIMER, CIBERSORT, QUANTISEQ, MCPcounter, xCell, and EPIC methods. The ESTIMATE algorithm provided stromal and immune scores. WGCNA identified key gene modules correlated with immune infiltration. Prognostic significance of these genes was assessed using univariate Cox regression, Kaplan-Meier analysis, and nomogram construction. Single-cell RNA sequencing data from TISCH2 was used to explore gene expression correlations across cell types. We also examined correlations of LDOC1 with TMB, MSI, NEO, and tumor purity, and predicted immunotherapy responses using TIDE and Submap analyses. Drug sensitivity was analyzed using GDSC data. RESULTS: Significant variations in M2 macrophage levels were found between tumor and normal tissues. WGCNA identified three key gene modules. Univariate Cox regression highlighted DMPK and LDOC1 as significant prognostic genes. Pan-cancer analysis showed LDOC1 as a crucial prognostic marker across various cancers, with strong correlations to multiple pathways. Single-cell analysis revealed distinct expression patterns of DMPK and LDOC1. In COAD, LDOC1 expression correlated significantly with immune checkpoints and tumor microenvironment scores. TIDE and Submap analyses suggested better immunotherapy response in low LDOC1 groups. Drug sensitivity analysis identified eight potential therapeutic agents. CONCLUSION: This study underscores the importance of M2 macrophages and LDOC1 in COAD, highlighting their potential as prognostic markers and therapeutic targets, paving the way for personalized treatments.