Single-cell transcriptomics reveals over-activated reactive oxygen species pathway in hepatocytes in the development of hepatocellular carcinoma
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View abstract on PubMed
Summary
This summary is machine-generated.Reactive oxygen species (ROS) pathway is overactive in hepatocellular carcinoma (HCC) hepatocytes, correlating with poor prognosis. Targeting ROS and JUND may offer new precision treatments for HCC.
Area Of Science
- Oncology
- Molecular Biology
- Bioinformatics
Background
- Hepatocellular carcinoma (HCC) is a leading cause of cancer mortality globally, characterized by significant tumor heterogeneity.
- The specific role of reactive oxygen species (ROS) in HCC pathogenesis remains underexplored.
Purpose Of The Study
- To investigate the role of ROS in HCC development using single-cell RNA sequencing.
- To identify molecular mechanisms and cellular interactions driving HCC progression related to ROS.
Main Methods
- Single-cell RNA sequencing (scRNA-seq) analysis of HCC and adjacent tissues using Seurat and CellMarker.
- Pathway analysis with DAVID and MsigDB, transcription factor network mapping with SCENIC, and cellular communication analysis with CellChat.
- Identification of cell subpopulations and subgrouping of hepatocytes based on ROS pathway activity.
Main Results
- Six major cell subpopulations were identified, with hepatocytes being the most abundant in both cancer and normal tissues.
- The ROS pathway was significantly activated in HCC hepatocytes, correlating positively with energy metabolism pathways.
- GPX4+ hepatocytes, exhibiting the highest ROS activity, were associated with a worse HCC prognosis, with JUND identified as a key regulatory factor.
- Interactions between GPX4+ hepatocytes and immune cells (T cells, M2 macrophages) were found to promote HCC malignancy.
Conclusions
- The ROS pathway is aberrantly activated in HCC hepatocytes, contributing to disease progression.
- GPX4+ hepatocytes with high ROS activity interact with immune cells, facilitating HCC development.
- Developing molecular subtypes and risk scores based on the ROS pathway and JUND is recommended for precise HCC treatment.
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