Integrated single-cell RNA-seq analysis identifies immune heterogeneity associated with KRAS/TP53 mutation status and tumor-sideness in colorectal cancers

• DOI: 10.3389/fimmu.2022.961350
• Publication Date: 2022-09-12T06:44:03Z
• Authors: Xiaoyu Liu; Xu Xu; Zhuozhuo Wu; Qungang Shan; Ziyin Wang; Zhiyuan Wu; Xiaoyi Ding; Wei Huang; Zhongmin Wang
• Keywords: Immune checkpoint

Background The main objective of this study was to analyze the effects KRAS/TP53 mutation status and tumor sideness on immune microenvironment colorectal cancer using integrated scRNA-seq data. Methods A total 78 datasets, comprising 42 treatment-naive tumors, 13 adjacent tissues 23 normal mucosa were included. Standardized Seurat procedures applied identify cellular components with canonical cell marks. batch-effect assessed corrected harmony algorithm. scMetabolism algorithm used for single-cell metabolic analysis. results clinical significance further validated immunofluorescent-staining TCGA-COAD datasets. Immune-infiltration scores bulk-RNA-seq data estimated ssGSEA. presto-wilcoxauc differentially enriched genes or pathways across different subgroups. Two-sided p-value less than 0.05 considered statistically significant. Results We refined landscape functional subtypes, especially T cells myeloid cells, mucosa, tissue. existence function two states exhausted CD8 + (Tex) subtypes in cancer, FOLR2 LYVE1 macrophages indicating unfavorable prognosis identified validated. diverse reshaped checkpoint ligands/receptors (ICLs/ICRs) expression pattern. Importantly, dual mutations significantly reduced major energy functions promoted cell-to-cell communications towards immunosuppression cancers. revealed LAG3, CD24-SIGLEC10 HBEGF-CD9 as potential therapeutic targets mutant Conclusions that underwent a gradual remodeling an enrichment immunosuppressive from regions Moreover, we heterogeneity tumor-infiltrating suggested may impair antitumor immunity by reducing metabolism reshaping interactions toward immunosuppression.