Integrated multi-omics unveils novel immune signature for predicting prognosis in colon cancer patients

Background Colon cancer, a prevalent malignancy, is subject to intricate immune modulation, which substantially affects both treatment efficacy and prognostic outcomes. Furthermore, colon cancer is highly heterogeneous, and our comprehensive understanding of its immune microenvironment has not yet been fully realized. There is still ample opportunity for in-depth investigation into the composition and interactions of immune cells within colon cancer, as well as their implications for disease prognosis. Methods and Results In this study, we employed single-cell data from colon cancer to distinguish immune cells from non-immune cells through cluster analysis. Furthermore, we conducted an in-depth analysis of myeloid and T cells, which were categorized into 20 distinct cell subpopulations. Functional enrichment analysis revealed T cells' active involvement in the Fatty Acid Metabolism and Adipogenesis pathways, while immune checkpoint-associated genes (ICGs) were notably upregulated in CD8 ⁺ T cells. Subsequent analysis involved calculating gene scores to characterize cell subpopulations, which, when combined with patient survival time analysis, revealed a significant association between the gene characterization score (referred to as "imm-score") and the survival of colon cancer patients. Specifically, the presence of CD8 ⁺ -ANXA1 ^hi -T cells was linked to shortened overall survival in the high imm-score subgroup. Subsequently, combined with genomic analysis, patients in the high imm-score subgroup exhibited elevated tumor mutation burden (TMB) and heightened activity in both the epithelial-mesenchymal transition (EMT) and Notch signaling pathway. Finally, according to our new algorithm, scores calculated predicted the effectiveness of immunotherapy for patients. The results revealed that patients with lower scores could achieve better therapeutic outcomes with immunotherapy. Conclusion This study offers an extensive analysis of the interplay between T cells and myeloid cells within colon cancer tissues, exploring their impact on the survival and prognosis of colon cancer patients. Additionally, it unveils the potential significance of the imm-score in colon cancer, potentially indicating a poor prognosis and providing novel insights into the immune-regulatory mechanisms underlying the disease.