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Updated: Jan 13, 2026
Comparing Metastatic Clear Cell Renal Cell Carcinoma Model Established in Mouse Kidney and on Chicken Chorioallantoic Membrane
Published on: February 8, 2020
Deciphering the molecular networks of 3-methylcholanthrene-induced clear cell renal cell carcinoma through
Yuzhe Su1, Peihuang Chen2, Yaoan Wen1
1Department of Urology, Fujian Medical University Union Hospital, Fuzhou, Fujian, 350001, China.
Abstract:
Exposure to 3-Methylcholanthrene (3-MC) may be associated with the development and progression of clear cell renal cell carcinoma (ccRCC); however, its underlying molecular mechanisms remain unclear. We conducted differential expression analyses across multiple datasets to identify target genes linked to ccRCC. By integrating SHapley Additive exPlanations (SHAP) with machine learning algorithms, network toxicology and molecular docking, we investigated the binding interactions between 3-MC and these target proteins. A total of 99 genes were identified as potential targets involved in 3-MC-induced ccRCC pathogenesis. Four core genes (GPC3, PIK3C2G, PPARA, and TRPA1) were selected through machine learning approaches. SHAP analysis demonstrated the combined contribution of these genes to the model's predictive performance. GPC3, PIK3C2G, and PPARA were significantly downregulated, whereas TRPA1 was upregulated (P < 0.05). Survival analysis using data from The Cancer Genome Atlas (TCGA) revealed significant differences in patient survival based on the expression levels of these genes. Molecular dynamics simulations validated the structural stability of the interaction between 3-MC and PPARA. These findings suggest that 3-MC promotes ccRCC pathogenesis by targeting specific genes.
Insights
3-Methylcholanthrene exposure may drive clear cell renal cell carcinoma (ccRCC) by affecting key genes like GPC3, PIK3C2G, PPARA, and TRPA1. These molecular changes impact ccRCC progression and patient survival, revealing new therapeutic targets.
Area of Science:
- Oncology
- Molecular Biology
- Toxicology
Background:
- 3-Methylcholanthrene (3-MC) exposure is linked to clear cell renal cell carcinoma (ccRCC) development.
- The specific molecular mechanisms underlying 3-MC's role in ccRCC remain largely unknown.
Purpose of the Study:
- To identify genes targeted by 3-MC in ccRCC pathogenesis.
- To elucidate the molecular mechanisms of 3-MC-induced ccRCC.
Main Methods:
- Differential gene expression analysis across multiple datasets.
- Integration of SHapley Additive exPlanations (SHAP) with machine learning, network toxicology, and molecular docking.
- Survival analysis using The Cancer Genome Atlas (TCGA) data and molecular dynamics simulations.
Main Results:
- Identified 99 potential target genes involved in 3-MC-induced ccRCC.
- Selected four core genes (GPC3, PIK3C2G, PPARA, TRPA1) using machine learning; SHAP analysis confirmed their predictive importance.
- Observed significant downregulation of GPC3, PIK3C2G, PPARA, and upregulation of TRPA1, correlating with patient survival outcomes.
- Validated the structural stability of 3-MC and PPARA interaction via molecular dynamics.
Conclusions:
- 3-Methylcholanthrene promotes ccRCC pathogenesis through specific molecular targets.
- The identified core genes (GPC3, PIK3C2G, PPARA, TRPA1) play crucial roles in 3-MC-induced ccRCC.
- These findings offer insights into ccRCC development and potential therapeutic strategies targeting 3-MC pathways.
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