免疫系统
间质细胞
肿瘤微环境
免疫疗法
生物
转录组
癌变
癌症研究
结直肠癌
表型
癌症
免疫学
基因
基因表达
遗传学
作者
Wenqin Luo,Weixing Dai,Qingguo Li,Shaobo Mo,Lingyu Han,Xiuying Xiao,Ruiqi Gu,Wenqiang Xiang,Ye Li,Renjie Wang,Ye Xu,Sanjun Cai,Guoxiang Cai
摘要
Ferroptosis is a non-apoptotic form of cell death recognized in recent years. Nonetheless, the potential role of ferroptosis-associated genes in immune regulation and tumor microenvironment formation remains unknown. In this study, we characterized the ferroptosis-associated patterns of colorectal cancer through integrative analyses of multiple datasets with transcriptomics, genomics, and single-cell transcriptome profiling. Three distinct ferroptosis-associated clusters (FAC1, FAC2 and FAC3) were identified from 1251 CRC bulk samples, which were associated with different clinical outcomes and biological pathways. The TME characterization revealed that the three patterns were highly consistent with known immune profiles: immune-desert (FAC1), immune-inflamed (FAC2) and immune-excluded (FAC3), respectively. Ferroptosis-associated immune and stromal-activated genes were obtained and characterized by corresponding function in CRC tumorigenesis. Further single-cell analyses identified the ferroptosis-associated immune responding tumor cells and ferroptosis-associated stromal cells infiltration pattern. Based on the Fersig score, which was extracted from the ferroptosis phenotype-related signature, patients with lower Fersig score were characterized by prolonged survival time and effective immune responses. Collectively, we uncovered the ferroptosis-associated patterns associated with TME diversity and immune response phenotype. The Fersig we constructed could be the potential therapeutic target genes to improve the efficacy of patients' immunotherapy. The Fersig scoring scheme could enhance the understanding of TME infiltration associated with ferroptosis and prediction of immunotherapy efficacy.
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