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Updated: Jan 9, 2026
A Syngeneic Mouse Model of Metastatic Renal Cell Carcinoma for Quantitative and Longitudinal Assessment of Preclinical Therapies
Published on: April 12, 2017
Yang-deficiency constitution drives poor outcomes in clear cell renal cell carcinoma by modulating the tumour immune
Boon Seng Kho1, Zongyuan Zhou2, Rui Liu1
1Department of Traditional Chinese Medicines (TCMs) Pharmaceuticals, School of Traditional Chinese Pharmacy, China Pharmaceutical University, Nanjing, China.
Background:
Clear cell renal cell carcinoma (ccRCC) is the most common subtype of kidney cancer, often diagnosed at advanced stages due to a lack of reliable early biomarkers. Recent studies suggest that the traditional Chinese medicine (TCM) body constitution, particularly the Yang-Deficiency Constitution (YDC), may influence tumour development by altering the immune microenvironment. However, the mechanistic connection between YDC and ccRCC prognosis remains largely unexplored.
Objective:
This study aims to elucidate the impact of YDC on the immune landscape and clinical outcomes of ccRCC and to identify novel prognostic biomarkers and potential herbal therapeutic agents guided by YDC characteristics.
Methods:
We integrated bulk transcriptomic data from 12 YDC-classified individuals and 530 ccRCC patients, alongside single-cell RNA-seq profiles from one PBMC and two ccRCC tumour samples. Through differential expression analysis, WGCNA, and machine learning-based survival modelling, we identified YDC-related biomarkers and assessed their immunological relevance using ESTIMATE, CIBERSORT, and CellChat. A gene expression-based scoring framework (GSVA) was developed to systematically prioritize 622 herbal ingredient perturbations for their potential survival benefits. Key ingredients were further validated through molecular docking and experimental assays.
Results:
Patients with YDC-associated ccRCC exhibited poorer survival. Nine intersecting genes were screened and used to construct a prognostic model, whereby seven key biomarkers-MXD3, PLCB2, CCDC88B, DEF6, IFNG, TBC1D10C, and PLEKHN1-were significantly influenced the prognosis of renal cancer. These genes were found to modulate immune cell populations, particularly CD8+ T cells, Tregs, and M1 macrophages, with IFNG serving as a central regulatory hub. Baicalein was identified and validated as a promising therapeutic agent targeting IFNG.
Conclusion:
This study highlights the crucial role of YDC in shaping the immune microenvironment and influencing survival in ccRCC. By integrating constitution-based stratification, immune profiling, and herbal medicine screening, we offer a unique framework for biomarker discovery and propose baicalein as a potential YDC-targeted adjuvant therapy.
Insights
Yang-Deficiency Constitution (YDC) impacts kidney cancer (ccRCC) survival by altering the immune microenvironment. This study identifies YDC-related biomarkers and baicalein as a potential therapy for ccRCC.
Area of Science:
- Oncology
- Immunology
- Traditional Chinese Medicine (TCM)
Background:
- Clear cell renal cell carcinoma (ccRCC) lacks early biomarkers, often diagnosed at advanced stages.
- Traditional Chinese Medicine (TCM) Yang-Deficiency Constitution (YDC) may influence ccRCC via the immune microenvironment.
- The mechanistic link between YDC and ccRCC prognosis is underexplored.
Purpose of the Study:
- To investigate the impact of YDC on ccRCC immune landscape and clinical outcomes.
- To identify novel prognostic biomarkers and potential herbal therapies for ccRCC based on YDC.
- To develop a framework for YDC-guided ccRCC biomarker and therapy discovery.
Main Methods:
- Integrated bulk and single-cell RNA-seq data from ccRCC patients stratified by YDC.
- Employed differential expression analysis, WGCNA, and machine learning for biomarker identification.
- Utilized GSVA and molecular docking to screen and validate herbal agents, focusing on immune modulation.
Main Results:
- YDC-associated ccRCC patients showed poorer survival.
- A seven-gene prognostic model (including IFNG) significantly impacted ccRCC prognosis and immune cell populations (CD8+ T cells, Tregs, M1 macrophages).
- Baicalein was identified and validated as a promising therapeutic targeting IFNG for YDC-associated ccRCC.
Conclusions:
- YDC plays a critical role in ccRCC immune microenvironment and patient survival.
- The study provides a novel framework integrating constitution, immunity, and herbal medicine for ccRCC research.
- Baicalein emerges as a potential adjuvant therapy for ccRCC in patients with YDC.
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