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Updated: May 9, 2026
The Use of Reverse Phase Protein Arrays (RPPA) to Explore Protein Expression Variation within Individual Renal Cell Cancers
Published on: January 22, 2013
Integrating single-cell multi-omics and machine learning to reveal triaptosis heterogeneity in clear cell renal cell
Haojie Dai1,2, Renjun Lu1,2,3, Mingcong Zhang4
1The Affiliated Liyang People's Hospital of Kangda College of Nanjing Medical University, Liyang Branch Hospital of Jiangsu Province Hospital, Liyang, Changzhou, Jiangsu, China.
Abstract:
Triaptosis, an emerging form of cell death, remains poorly characterized in terms of its heterogeneity within clear cell renal cell carcinoma (ccRCC). Utilizing single-cell transcriptomics, we delineate a landscape of triaptosis heterogeneity and identify monocytes and macrophages as exhibiting the highest triaptosis activity, which further increases upon terminal differentiation. These high-activity cells also demonstrate enhanced pro-angiogenic signaling toward endothelial cells. Within epithelial cells, subpopulations with the strongest triaptosis activity are located at the late differentiation stage and are closely associated with ccRCC traits. Spatial transcriptomic analysis reveals a decline in triaptosis activity with increasing distance from the tumor epithelial core. The epithelial cluster with the highest triaptosis activity showed reduced metabolic activity. In bulk transcriptome analysis, patients with high epithelial triaptosis activity infiltration exhibited improved prognosis, broader immune activation, and similarly suppressed metabolism. We subsequently developed a robust 4-gene prognostic signature based on module genes derived from high-triaptosis epithelial subpopulations. This model showed strong performance in prognostic stratification, immunotherapy guidance, and chemotherapy response prediction. Finally, we identified SLC25A37 as a core oncogenic gene within the signature and proposed Yohimbic acid among several potential molecularly targeted therapeutics.
Insights
Triaptosis, a cell death form, varies in clear cell renal cell carcinoma (ccRCC). Monocytes, macrophages, and late-stage epithelial cells show high activity, impacting prognosis and treatment strategies.
Area of Science:
- Oncology
- Cell Biology
- Immunology
Background:
- Triaptosis is an emerging cell death pathway with poorly understood heterogeneity in clear cell renal cell carcinoma (ccRCC).
- Understanding triaptosis variations is crucial for developing targeted therapies in ccRCC.
Purpose of the Study:
- To investigate the heterogeneity of triaptosis in ccRCC using single-cell and spatial transcriptomics.
- To identify cell types and differentiation stages associated with high triaptosis activity.
- To develop a prognostic signature and identify therapeutic targets based on triaptosis patterns.
Main Methods:
- Single-cell RNA sequencing (scRNA-seq) to analyze triaptosis heterogeneity.
- Spatial transcriptomics to map triaptosis activity within the tumor microenvironment.
- Bulk transcriptome analysis for correlating triaptosis with patient prognosis and immune profiles.
- Bioinformatic analysis to develop a gene-based prognostic signature.
Main Results:
- Monocytes and macrophages exhibit the highest triaptosis activity, increasing with differentiation.
- Late-stage epithelial cell subpopulations show strong triaptosis activity, linked to ccRCC traits and reduced metabolism.
- Triaptosis activity decreases with distance from the tumor core.
- High epithelial triaptosis infiltration correlates with improved prognosis, immune activation, and suppressed metabolism.
- A 4-gene prognostic signature demonstrated strong performance in stratification, immunotherapy, and chemotherapy prediction.
- SLC25A37 was identified as a core oncogenic gene, and Yohimbic acid was proposed as a potential therapeutic.
Conclusions:
- Triaptosis exhibits significant heterogeneity in ccRCC, with distinct roles in immune and epithelial cells.
- Epithelial triaptosis activity serves as a promising prognostic biomarker and potential therapeutic target in ccRCC.
- The developed 4-gene signature and identified oncogene/therapeutic offer new avenues for ccRCC management.
