IFI30 remoulds immune microenvironment and macrophage function to promote colorectal cancer and atherosclerosis

Background Colorectal cancer (CRC) and atherosclerosis (AS) are both chronic inflammatory diseases that may share immune-related genes (IRGs) and regulatory mechanisms. This study aimed to identify commonly dysregulated IRGs in CRC and AS, and to investigate their clinical significance and molecular functions. Methods Transcriptomic, single-cell RNA sequencing (scRNA-seq), and somatic mutation data from the TCGA-COAD and GEO databases were integrated to identify overlapping dysregulated IRGs in CRC and AS. Comprehensive analyses, including survival analysis, immune infiltration assessment (CIBERSORT, ssGSEA, ESTIMATE), functional enrichment, drug sensitivity prediction, and single-cell analysis, were conducted to evaluate the prognostic relevance and immunological role of the core gene IFI30 . The expression level of core genes was verified by staining pathological sections of stored files. Results A total of 102 IRGs were found to be commonly dysregulated in both CRC and AS. Among them, IFI30 was notably upregulated in both diseases, with its upregulation predicting poor prognosis in CRC (HR = 1.68, p  < 0.05). Immune profiling revealed that elevated IFI30 expression was linked to higher immune scores and increased infiltration of macrophages and T cells. IFI30 expression also showed a positive linkage with genes in the interleukin, interferon, and TNF families. scRNA-seq indicated that IFI30 is predominantly expressed in macrophages, where it may promote M2 polarization by modulating oxidative phosphorylation and lipid metabolism pathways. Furthermore, high IFI30 expression was linked to reduced sensitivity to immunotherapy and certain chemotherapeutic agents, as well as increased mutation frequencies in genes such as KIF26A and TTN . Immunohistochemical experiments confirmed that the expression of IFI30 in colorectal cancer tissue and unstable carotid plaque increased significantly. Conclusion IFI30 is a critical immune regulatory gene commonly involved in both CRC and AS, with functional evidence pointing to its role in modulating macrophage-driven immune remodeling. These characteristics position IFI30 as a biomarker of clinical relevance and a candidate for future targeted therapies. These findings provide new insights into shared immunopathological mechanisms across chronic inflammatory diseases.