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Transcriptomic and Single-Cell Analyses Reveal a Prognostic Mitochondria- and Immunity-Related Risk Signature in
Jiangbo Ai1,2, Zhidong Peng1,2, Peichuan Xu1,2
1Department of Orthopaedics, The Second Affiliated Hospital, Jiangxi Medical College, Nanchang University, 330006 Nanchang, Jiangxi, China.
Frontiers in Bioscience (Landmark Edition)
|July 30, 2026
Summary
This study identified four key genes (GSTP1, CAT, TNFSF10, PRKCA) linked to mitochondria and immunity that predict osteosarcoma (OS) patient survival. Protein kinase Cα (PRKCA) was found to promote OS cell invasion, migration, and proliferation.
Area of Science:
- Oncology
- Immunology
- Mitochondrial Biology
Background:
- Osteosarcoma (OS) pathogenesis involves mitochondrial dysfunction and immune cell dysregulation.
- The prognostic significance of mitochondria-related genes (MRGs) and immune-related genes (IRGs) in OS is not well understood.
Purpose of the Study:
- To identify prognostic genes related to both mitochondria and immunity in osteosarcoma.
- To develop a predictive model for OS patient survival.
- To investigate the role of specific genes in the OS microenvironment and cellular functions.
Main Methods:
- Utilized differential gene expression and weighted gene co-expression network analysis on public OS datasets.
- Integrated analysis of differentially expressed genes (DEGs), key module genes, MRGs, and IRGs to identify candidate prognostic genes.
- Constructed and validated a risk model using regression analysis and proportional hazards testing; performed single-cell and in vitro analyses.
Main Results:
- Identified GSTP1, CAT, TNFSF10, and PRKCA as prognostic genes for OS, forming the basis of a predictive risk model and nomogram.
- Observed significant differences in immune cell infiltration and checkpoint molecules between high-risk and low-risk groups.
- Single-cell analysis highlighted M1 macrophages as relevant, with distinct expression patterns of identified genes during differentiation; in vitro studies confirmed PRKCA promotes OS cell invasion, migration, and proliferation.
Conclusions:
- GSTP1, CAT, TNFSF10, and PRKCA are identified as prognostic markers for osteosarcoma, linking mitochondrial and immune functions.
- In vitro validation supports PRKCA's role in promoting OS progression, suggesting potential therapeutic applications.
- These findings offer novel insights for predicting OS prognosis and developing targeted therapies.
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