Integrated muti-omics analyses and experimental validation reveal the clinical and biological Significances of APBB1IP in Colon Cancer

Abstract

Background： Tumor-associated macrophages(TAMs), especially M2 macrophages, plays a critical role in Colorectal cancer initiation, promotion, and metastasis. However, the underlying mechanisms still remain unresolved. Methods：The profile of ATAC-seq was employed to detect genes with open chromatin. The RNA-seq was used to identify differentially expressed genes (DEGs) and those DEGs with open chromatin in promoter regions were identified as hub gene. Then, CIBERSORT, quanTIseq and XCELL algorithm were employed to quantified the expression of M2 macrophages and Pearson correlation analysis was used to identified the relationship with M2 macrophages and hub gene. After that, the macrophages profile and scRNA-seq profile were used to identify the gene expression in different phenotype macrophage. GO/KEGG analysis, GSEA, GSVA were used for gene function analysis. Finally, the target gene which promote M2 macrophages polarization were further explored by experiment. Results：In this study, we acquired 15,650 genes with open chromatin in promoter regions and 3,241 genes were identified as differential expression genes with open chromatin. Integrated CIBERSORT, quanTIseq and XCELL algorithm, we identified 72 genes were correlated with M2 macrophages (r>0.2, p<0.05). According to the macrophages profile from GEO database, 2 genes were identified as differential expressed genes which high expressed in M2 macrophages. By applying scRNA-seq, APBB1IP was the only gene expressed in macrophage and high expressed in M2 phenotype. M2 macrophage polarization were inhibited after knockdown of APBB1IP in vitro experiments. Conclusion：APBB1IP, characterized by chromatin accessibility, downregulated in patients with COAD and induced M2 macrophage polarization.