HOMER3 and its correlation with immune-infiltrating M2 macrophages in colorectal cancer

Homer scaffold protein 3 (HOMER3) is a member of the HOMER family of postsynaptic density scaffolding proteins, but its function in CRC remains unclear. This study aimed to elucidate the role of HOMER3 in CRC by analyzing extensive databases and evaluating real-world clinical samples. Additionally, multivariate Cox regression analysis and functional enrichment analysis were utilized to identify the pathways and functions potentially regulated by HOMER3 and its co-expressed genes. Database analysis unveiled a significant upregulation of HOMER3 in CRC, correlating with diminished survival metrics and adverse clinical indicators such as advanced pT stage and pN stage. Experimental analysis of real-world samples showed that HOMER3 expression was elevated in CRC and was associated with advanced pN and pT stages. Elevated HOMER3 expression emerged as an independent prognostic marker for poorer outcomes in CRC patients. The functional enrichment analysis underscored HOMER3’s oncogenic potential, implicating it in key regulatory mechanisms of tumorigenesis and its association with diverse immune cell infiltration, notably macrophages. We observed a positive correlation between M2 macrophages and HOMER3 expression, a finding that was further corroborated by immunofluorescence staining. HOMER3 may serve as a valuable prognostic biomarker in CRC, and its expression correlates with the infiltration of M2-polarized macrophages within the tumor immune microenvironment. These findings underscore the necessity for further investigations into the functional role of HOMER3 in CRC progression and its underlying immune regulation mechanisms.