2. Academic Validation
  3. Plasma secretory protein genes in hepatocellular carcinoma and heart failure: Comorbidity and biological function exploration

Plasma secretory protein genes in hepatocellular carcinoma and heart failure: Comorbidity and biological function exploration

  • Mol Immunol. 2025 Dec:188:45-61. doi: 10.1016/j.molimm.2025.10.009.
Lizhi Cao 1,  Xiaoying Wang 2,  Zhongping Ning 2,  Fandi Xie 3,  Xiaodan Li 2,  Yongting Chen 2,  Qian Geng 2,  Junchi Liu 2,  Qian Zhu 4,  Linlin Ma 5,  Yanfei Li 6
Affiliations

Affiliations

  • 1 Shanghai University of Medicine and Health Sciences Affiliated Zhoupu Hospital, Shanghai, China; Department of Equipment, Affiliated Hospital of Nanjing University of Chinese Medicine (Jiangsu Province Hospital of Chinese Medicine), Nanjing, Jiangsu, China.
  • 2 Shanghai University of Medicine and Health Sciences Affiliated Zhoupu Hospital, Shanghai, China.
  • 3 Shanghai Jiangwan Hospital, Shanghai, China.
  • 4 Shanghai University of Medicine and Health Sciences Affiliated Zhoupu Hospital, Shanghai, China. Electronic address: [email protected].
  • 5 Shanghai University of Medicine and Health Sciences Affiliated Zhoupu Hospital, Shanghai, China. Electronic address: [email protected].
  • 6 Shanghai University of Medicine and Health Sciences Affiliated Zhoupu Hospital, Shanghai, China. Electronic address: [email protected].
PMID: 41192015 DOI: 10.1016/j.molimm.2025.10.009
Abstract

Background: This research aimed to elucidate the roles of plasma secretory protein genes in mediating the comorbid effects between hepatocellular carcinoma (HCC) and heart failure (HF).

Methods: A comprehensive analysis utilizing Weighted Gene Co-expression Network Analysis (WGCNA), differential expression analysis, and advanced deep learning techniques was conducted to identify three plasma-secreted protein genes (Ficolin-3: FCN3, Fibroblast Activation Protein: FAP, High Mobility Group Box 2: HMGB2) as key players in the comorbid interplay between HCC and HF.

Results: Validation experiments confirmed the significant biological functions of these genes in disease pathogenesis. Additionally, dexamethasone and catechins were identified as promising candidates for pharmacological intervention in the prevention of HCC and HF.

Conclusion: These findings unveil potential mechanistic pathways of comorbidity between HCC and HF, providing novel biological markers and therapeutic targets for the prognostic evaluation and treatment of these conditions, with substantial implications for refining clinical diagnosis and therapeutic strategies.

Keywords

Cell Co-culture Model; Comorbid Pathways; Heart Failure; Hepatocellular Carcinoma; Machine Learning; Molecular Docking; Multi-omics; Plasma Secretory Proteins; Therapeutic Targets.

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