Systematic analysis and experimental validation of the prognostic and immunological effects of SPP1 tumor-associated macrophage features in colorectal cancer

Abstract

Purpose Tumor associated macrophages (TAM) influence colorectal cancer (CRC) development, and their clinical significance has been widely established. We intend to depict a full macrophage landscape in order to increase our understanding of CRC heterogeneity and give improved precision medicine techniques. Methods Use Seurat and Cellchat to conduct single cell analysis on GSE178341 to determine the interaction between cells and understand the influence of core cell subsets on immune response. SsGSEA was used to quantify the immune related cells of TCGA patients and further cluster them into subtypes. The effectiveness of combined COX and LASSO, SPP1 TAM characteristics in predicting prognosis was validated in several GEO datasets. Then, Cell line culture and Quantitative real-time PCR were used to validate the hub genes of SPP1 TAM features. Results and Conclusion To summarize, we built a more comprehensive macrophage atlas to highlight the wide range and heterogeneity of macrophages present in people at various MMR stages. SPP1 TAM is not only enriched in dMMR patients, but also shows two characteristics of immune response, which may explain the reason why some dMMR patients have poor response to immunotherapy. The prognosis model constructed by Hub DEG SPP1 related to it has different responses to immune response and chemotherapy drugs, which provides new clues to inhibit the potential efficacy of SPP1 TAM.