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Published on: May 3, 2024
Integration of Single-cell Sequencing Analysis Reveals Disulfidptosis Related Molecular Subtype and Novel Prognosis
Houxi Li1, Tian Deng2, Mingyue Yan1
1Department of Orthopedics, the Affiliated Hospital of Qingdao University, Qingdao, 266000, China.
Background:
Osteosarcoma (OS) is one of the most common primary malignancies in children and adolescents. Disulfidptosis, a newly identified form of metabolically induced programmed cell death triggered by disulfide stress, has not yet been explored in OS.
Methods:
We integrated data from public databases and applied a series of bioinformatics approaches, including clustering analysis to classify OS subtypes, and Cox and LASSO regression analysis to identify prognostic disulfidptosis-related genes (DRGs). Enrichment analysis was performed to explore the biological pathways associated with DRG-related molecular subtypes. The immune infiltration landscape was assessed to understand the tumor microenvironment in different risk subgroups. Additionally, drug sensitivity analysis was conducted to evaluate the potential clinical therapeutic strategies of the identified DRG score subgroups. The distribution of DRG expression across OS cell subtypes was further analyzed using single-cell RNA sequencing. In vitro assays, including Western blotting, qRT-PCR, and cell migration and invasion assays, were conducted to validate POLR1D expression and function in OS cells.
Results:
We established a DRG-based prognostic model that effectively stratifies OS patients into distinct risk groups with different survival outcomes. The model also revealed significant differences in immune cell infiltration between high and low DRG scores group, suggesting a link between disulfidptosis and the OS immune microenvironment. Drug sensitivity analysis indicated that the DRG signature could guide personalized therapeutic strategies. Single-cell RNA sequencing revealed heterogeneous expression of DRG signature across OS cell subtypes. Functional assays confirmed that POLR1D was aberrantly overexpressed in OS cells and promotes their migration and invasion, supporting its role as a potential oncogenic driver in OS.
Conclusion:
Our study is the first to investigate the role of DRGs for risk stratification in OS, providing new insights and targets into OS pathogenesis.
Insights
This study introduces disulfidptosis-related genes (DRGs) as novel biomarkers for osteosarcoma (OS) risk stratification. The findings reveal DRGs
Area of Science:
- Oncology
- Molecular Biology
- Bioinformatics
Background:
- Osteosarcoma (OS) is a common pediatric malignancy.
- Disulfidptosis, a programmed cell death pathway induced by disulfide stress, is a novel area of research.
- The role of disulfidptosis in OS remains unexplored.
Purpose of the Study:
- To investigate the role of disulfidptosis-related genes (DRGs) in osteosarcoma (OS).
- To develop a prognostic model for OS risk stratification based on DRGs.
- To explore the relationship between DRGs, the tumor immune microenvironment, and therapeutic strategies in OS.
Main Methods:
- Integrated public database analysis and bioinformatics approaches.
- Applied Cox and LASSO regression to identify prognostic DRGs.
- Utilized single-cell RNA sequencing and in vitro assays to validate findings.
Main Results:
- Developed a DRG-based prognostic model stratifying OS patients by survival.
- Identified significant differences in immune cell infiltration linked to DRG scores.
- Validated POLR1D as an oncogenic driver promoting OS cell migration and invasion.
Conclusions:
- This is the first study to explore DRGs for risk stratification in OS.
- The findings provide novel insights into OS pathogenesis and potential therapeutic targets.
- DRGs offer a promising avenue for personalized treatment strategies in OS.
