Identifying neutrophil-associated subtypes in ulcerative colitis and confirming neutrophils promote colitis-associated colorectal cancer

溃疡性结肠炎 结肠炎 转录组 结直肠癌 免疫系统 免疫学 生物 小桶 炎症性肠病 基因 流式细胞术 癌症研究 中性粒细胞胞外陷阱 基因表达 癌症 炎症 疾病 医学 遗传学 内科学
作者
Chen Zhang,Jiantao Zhang,Yanli Zhang,Zian Song,Jing Bian,Huanfa Yi,Zhanchuan Ma
出处
期刊:Frontiers in Immunology [Frontiers Media]
卷期号:14 被引量:30
标识
DOI:10.3389/fimmu.2023.1095098
摘要

Background Ulcerative colitis (UC) is a chronic inflammatory disease of the intestinal mucosa, the incidence of which has increased worldwide. There is still a lack of clear understanding of the pathogenesis of ulcerative colitis that ultimately leads to colitis-associated colorectal cancer. Method We download UC transcriptome data from the GEO database and pass the limma package in order to identify differentially expressed genes. Gene Set Enrichment Analysis (GSEA) was used to identify potential biological pathways. We identified immune cells associated with UC by CIBERSORT and Weighted co-expression network analysis (WGCNA). We used validation cohorts and mouse models to verify the expression of the hub genes and the role of neutrophils. Result We identified 65 differentially expressed genes in UC samples and healthy controls. GSEA, KEGG, and GO analyses displayed that DEGs were enriched in immune-related pathways. CIBERSORT analysis revealed increased infiltration of neutrophils in UC tissues. The red module, obtained by WGCNA analysis, was considered to be the most relevant module for neutrophils.Based on neutrophil-associated differentially expressed genes, UC patients were classified into two subtypes of neutrophil infiltration. We discovered that the highly neutrophil-infiltrated subtype B of UC patients had a higher risk of developing CAC. Five genes were identified as biomarkers by searching for DEGs between distinct subtypes. Finally, using the mouse model, we determined the expression of these five genes in the control, DSS, and AOM/DSS groups. The degree of neutrophil infiltration in mice and the percentage of MPO and pSTAT3 expression in neutrophils were analyzed by flow cytometry. In the AOM/DSS model, MPO and pSTAT3 expressions were significantly increased. Conclusions These findings suggested neutrophils might promote the conversion of UC into CAC. These findings improve our understanding of the pathogenesis of CAC and provide new and more effective insights into the prevention and treatment of CAC.
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