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Updated: Jul 3, 2026
08:25
Mass Cytometry Analysis of Systemic and Local Immune Responses in Hepatocellular Carcinoma
Published on: April 25, 2025
Multi-omics and spatial transcriptomics decode the ZDHHC9-driven hypoxia-immunosuppressive axis in hepatocellular
Haiyan Lu1, Lingzhen Kong2, Shidong Hu3
1Department of Oncology, Renji Hospital, School of Medicine, Chongqing University, The Fifth People's Hospital of Chongqing, Chongqing, China.
Frontiers in Oncology
|July 2, 2026
Summary
This study identifies ZDHHC9 as a key biomarker for hepatocellular carcinoma (HCC). Targeting ZDHHC9 shows promise for new HCC therapies by reducing tumor growth and improving the tumor microenvironment.
Area of Science:
- Oncology
- Molecular Biology
- Bioinformatics
Background:
- Hepatocellular carcinoma (HCC) presents limited treatment options, necessitating novel biomarkers and therapeutic targets.
- The role of protein palmitoylation and ZDHHC enzymes in HCC pathogenesis remains incompletely understood.
Purpose of the Study:
- To systematically analyze the ZDHHC family in HCC.
- To identify ZDHHC9 as a diagnostic and prognostic biomarker.
- To investigate the therapeutic potential of targeting ZDHHC9 in HCC.
Main Methods:
- Utilized TCGA and GEO databases for multi-omics analysis of ZDHHC family expression and prognostic value.
- Employed machine learning algorithms for biomarker identification and developed a multi-gene prognostic signature.
- Conducted integrated single-cell and spatial transcriptomics to characterize the tumor microenvironment.
- Performed functional validation of ZDHHC9 using in vitro and in vivo models.
Main Results:
- ZDHHC9 was identified as a key prognostic factor and top diagnostic biomarker for HCC.
- A robust multi-gene prognostic signature was constructed and validated.
- High ZDHHC9 expression correlated with an immunosuppressive tumor microenvironment and therapy resistance.
- ZDHHC9 is upregulated in malignant hypoxic epithelial cells and its depletion inhibits HCC progression.
Conclusions:
- The ZDHHC family profiling establishes ZDHHC9 as a novel diagnostic and prognostic biomarker for HCC.
- ZDHHC9 is a promising therapeutic target, potentially by modulating hypoxia and immune suppression.
- The study provides a comprehensive understanding of ZDHHC family's role in HCC development.
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