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Updated: Mar 25, 2026
A Syngeneic Mouse Model of Metastatic Renal Cell Carcinoma for Quantitative and Longitudinal Assessment of Preclinical Therapies
Published on: April 12, 2017
Integrative Genomic and Single-Cell Insights Into Efferocytosis-Mediated Immune Regulation in Clear Cell Renal Cell
Bing Shi1,2, Minghao Deng1,2, Jiakang Ma3
1Department of Urology, Nantong Hospital of Traditional Chinese Medicine, Nantong, 226001, China, ntzyy.com.
Background:
Efferocytosis, the phagocytic clearance of apoptotic cells, plays a key role in tumor progression and immune regulation, but its prognostic significance and molecular mechanisms in clear cell renal cell carcinoma (ccRCC) remain unclear.
Methods:
Four efferocytosis-related pathways were curated, and the pathway activities were quantified in ccRCC. Prognostic genes were identified by univariate Cox regression and used to construct linear survival models with multiple algorithms, with the optimal model selected by cross-validation. Associations between the risk score and tumor mutational burden (TMB), mutation profiles, and copy number variation (CNV) were subsequently evaluated. Multiomics integration highlighted RAC1 as a key risk gene, which was further examined using single-cell and spatial transcriptomics (ST) to characterize expression patterns, tumor microenvironment interactions, and pathway enrichments. Protein-level validation was performed using immunohistochemistry (IHC) data from the Human Protein Atlas.
Results:
Efferocytosis pathway activity was upregulated in ccRCC, increased with disease stage, and correlated with poorer survival. The ridge regression-based prognostic model demonstrated consistent predictive performance across independent datasets and was associated with higher TMB, specific mutation patterns, and increased CNV. Notably, RAC1, identified as the top weighted gene in the model, was overexpressed in association with copy number amplification, showing preferential enrichment in malignant core regions and strong links to oncogenic signaling.
Conclusion:
Efferocytosis activation characterizes aggressive ccRCC. The developed prognostic model and identification of RAC1 as a central effector link efferocytosis-related risk to immune remodeling and oncogenic signaling, providing potential biomarkers and therapeutic targets.
Insights
Efferocytosis, the clearance of dead cells, is active in aggressive clear cell renal cell carcinoma (ccRCC) and predicts poor outcomes. RAC1 is a key gene linking this process to tumor growth and immune changes.
Area of Science:
- Oncology
- Immunology
- Molecular Biology
Background:
- Efferocytosis is crucial for tumor progression and immune regulation.
- Its prognostic significance and molecular mechanisms in clear cell renal cell carcinoma (ccRCC) are not well understood.
Purpose of the Study:
- To investigate the role and prognostic value of efferocytosis in ccRCC.
- To identify molecular mechanisms and potential biomarkers associated with efferocytosis in ccRCC.
Main Methods:
- Quantified efferocytosis pathway activity in ccRCC using curated pathways.
- Developed and validated prognostic models using survival data and multiple algorithms.
- Evaluated associations between risk scores and tumor mutational burden (TMB), mutation profiles, and copy number variation (CNV).
- Integrated multiomics data, including single-cell and spatial transcriptomics (ST), to analyze RAC1 expression and tumor microenvironment interactions.
- Validated protein expression using immunohistochemistry (IHC) data.
Main Results:
- Efferocytosis pathway activity was elevated in ccRCC, correlating with advanced stage and poorer survival.
- A ridge regression-based prognostic model showed consistent predictive performance and was linked to higher TMB, specific mutations, and CNV.
- RAC1 was identified as a key risk gene, overexpressed with copy number amplification, and enriched in malignant regions, associated with oncogenic signaling.
Conclusions:
- Activated efferocytosis is a hallmark of aggressive ccRCC.
- The developed prognostic model and RAC1 highlight efferocytosis-related risks, immune remodeling, and oncogenic signaling, offering potential therapeutic targets and biomarkers.
