Identification of CTSK as a TLR-related critical biomarker in liver cirrhosis via integrative bioinformatics and pathological characterization.

Journal: Scientific reports
Published Date: Jul 17, 2025

Abstract

Liver cirrhosis (LC) is a common chronic disease worldwide with a poor prognosis, and its pathogenesis has not been fully elucidated. Toll-like receptors (TLRs) are crucial in LC progression. Here, we identified TLR-related genes, providing novel insights related to LC diagnosis, pathogenesis, and treatment. Data from public databases were analyzed using "limma" and WGCNA to screen candidate genes, and four hub genes (CXCL9, CXCL10, SPP1, CTSK) were selected through machine learning. These hub genes were validated through bioinformatics, quantitative real-time PCR (qRT-PCR), and immunohistochemistry (IHC). Both the hub genes and risk models demonstrated strong diagnostic potential for LC. The hub genes were enriched in various pathways and strongly correlated with immune infiltration. Subtypes characterized by different TLR signaling activity exhibited distinct immune responses. scRNA-seq analysis revealed significant differences in hub gene expression and TLR signaling activity across different cell types. ceRNA network analysis revealed interactions involving miRNAs, lncRNAs, and hub genes. Molecular docking supported the potential value of the hub genes as drug targets. In conclusion, TLR-related hub genes exhibit excellent diagnostic and therapeutic value in LC, and their dysregulation contributes to immune disorders and activation of pathogenic signaling pathways. CTSK may stimulate the TLR4-MyD88-NF-κB axis to facilitate LC progression.

Authors

  • Jiaxin Wang
    Faculty of Engineering, University of Toyama, Toyama-Shi 930-8555, Japan.
  • Ning Li
    Department of Respiratory and Critical Care Medicine, Center for Respiratory Medicine, the Fourth Affiliated Hospital of School of Medicine, and International School of Medicine, International Institutes of Medicine, Zhejiang University, Yiwu, China.
  • Xueyu Cang
    Department of Gastroenterology and Hepatology, The Second Affiliated Hospital of Harbin Medical University, Harbin, China.
  • Xuerong Liu
    School of Psychology, Third Military Medical University, Chongqing, China.
  • Ranyan Gao
    Department of Gastroenterology and Hepatology, The Second Affiliated Hospital of Harbin Medical University, Harbin, China.
  • Lingyi Xu
    Department of Gastroenterology and Hepatology, The Second Affiliated Hospital of Harbin Medical University, Harbin, China.
  • Fengchun Li
    Department of Gastroenterology and Hepatology, The Second Affiliated Hospital of Harbin Medical University, Harbin, China.
  • Xinyu Jiang
    Deutsches Elektronen-Synchrotron (DESY), Notkestraße 85, 22607 Hamburg, Germany.
  • Hongliang Chen
    Department of Gastroenterology and Hepatology, The Second Affiliated Hospital of Harbin Medical University, Harbin, China.
  • Xinyu Geng
    Department of Gastroenterology and Hepatology, The Second Affiliated Hospital of Harbin Medical University, Harbin, China.
  • Jihan Qi
    Department of Gastroenterology and Hepatology, The Second Affiliated Hospital of Harbin Medical University, Harbin, China.
  • Ram Prasad Chaulagain
    Department of Gastroenterology and Hepatology, The Second Affiliated Hospital of Harbin Medical University, Harbin, China.
  • Junchong He
    College of Health Caring Industry, Harbin Medical University (Daqing), Daqing, China.
  • Shizhu Jin
    Department of Gastroenterology and Hepatology, The Second Affiliated Hospital of Harbin Medical University, Harbin, China. drshizhujin@hrbmu.edu.cn.

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