Machine learning-based characterization of PANoptosis-related biomarkers and immune infiltration in ulcerative colitis: A comprehensive bioinformatics analysis and experimental validation.

Journal: International immunopharmacology
PMID:

Abstract

Ulcerative colitis (UC) is a heterogeneous autoimmune condition. PANoptosis, a new form of programmed cell death, plays a role in inflammatory diseases. This study aimed to identify differentially expressed PANoptosis-related genes (PRGs) involved in immune dysregulation in UC. Three key PRGs-BIRC3, MAGED1, and PSME2 were found using weighted gene co-expression network analysis (WGCNA) and machine learning. Immune infiltration analysis revealed that these key PRGs were associated with neutrophils, CD8+ T cells, activated CD4 T cells, and NK cells. Moreover, these key PRGs were significantly enriched in pathways related to inflammatory bowel disease, the IL-17 signaling pathway, and NOD-like receptor signaling pathway. The expression levels of the key PRGs were validated in various datasets, animal models, and UC intestinal tissue samples. Our findings confirmed the involvement of PANoptosis in UC and predict hub genes and immune characteristics, providing new insights for further investigations into UC pathogenic mechanisms and therapeutic strategies.

Authors

  • Changshan Wan
    Department of Gastroenterology and Hepatology, Tianjin Medical University General Hospital, Tianjin Institute of Digestive Diseases, Tianjin Key Laboratory of Digestive Diseases, Tianjin 300052, China.
  • Qiuyan Wu
    Department of Gastroenterology and Hepatology, Tianjin Medical University General Hospital, Tianjin Institute of Digestive Diseases, Tianjin Key Laboratory of Digestive Diseases, Tianjin 300052, China.
  • Yali Wang
    Department of Blood Transfusion, China-Japan Union Hospital, Jilin University, Changchun, China.
  • Yan Sun
    Department of Biochemistry, Albert Einstein College of Medicine, New York, NY, United States.
  • Tao Ji
    Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, National and Local Collaborative Engineering Center of Chinese Medicinal Resources Industrialization and Formulae Innovative Medicine, And Jiangsu Key Laboratory for High Technology Research of TCM Formulae, Nanjing University of Chinese Medicine, Nanjing, 210023, China.
  • Yu Gu
    Microsoft Research, Redmond, WA, USA.
  • Liwei Wang
    Department of Health Sciences Research, Mayo Clinic, Rochester, MN, USA.
  • Qiuyu Chen
    College of Automation and Electronic Engineering, Qingdao University of Science and Technology, Qingdao, China.
  • Zhen Yang
    CAS Max-Planck Partner Institute for Computational Biology, Shanghai Institute of Biological Sciences, 320 Yue Yang Road, Shanghai, 200031, China.
  • Yao Wang
    Department of Gastrointestinal Surgery, Zhongshan People's Hospital, Zhongshan, Guangdong, China.
  • Bangmao Wang
    Department of Gastroenterology, General Hospital of Tianjin Medical University, Tianjin Medical University, Tianjin, China.
  • Weilong Zhong
    Department of Gastroenterology and Hepatology, Tianjin Medical University General Hospital, Tianjin Institute of Digestive Diseases, Tianjin Key Laboratory of Digestive Diseases, Tianjin 300052, China. Electronic address: zhongweilong@tmu.edu.cn.