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Integrative Multi-Transcriptomic Uncovers Actionable Signatures and Drug Repurposing Candidates for
Yinnan Zhang1, Boon Seng Kho1, Xixi Wang2
1Department of TCMs Pharmaceuticals, School of Traditional Chinese Pharmacy, China Pharmaceutical University, Nanjing 211198, China.
Cancers
|July 28, 2026
Summary
This study identified four key genes (SCNN1G, CASR, KCNJ1, WNK4) linking hypertension and clear cell renal cell carcinoma (ccRCC). These genes may serve as biomarkers and therapeutic targets for ccRCC, with potential treatments identified.
Area of Science:
- Oncology
- Genetics
- Molecular Biology
Background:
- Hypertension is a known risk factor for clear cell renal cell carcinoma (ccRCC).
- The molecular links between hypertension and ccRCC remain largely unknown.
- This research investigates hypertension-related molecular signatures in ccRCC.
Purpose of the Study:
- To identify hypertension-related molecular signatures in ccRCC.
- To characterize potential hub genes involved in the hypertension-ccRCC association.
- To explore novel therapeutic targets and compounds for ccRCC.
Main Methods:
- Integrated multi-transcriptomic analysis of TCGA-KIRC data.
- Identification of hypertension-related differentially expressed genes (DEHRGs).
- Utilized WGCNA, machine learning, GSVA, survival, Mendelian randomization, spatial, and single-cell transcriptomics.
Main Results:
- Identified four hub genes: SCNN1G, CASR, KCNJ1, and WNK4, involved in ion transport and blood pressure regulation.
- Diagnostic models showed good performance; higher transcriptional activity correlated with poorer survival.
- Spatial and single-cell analyses revealed heterogeneity and identified epicatechin gallate (ECG) and pseudoginsenoside-F11 as potential therapeutic compounds.
Conclusions:
- SCNN1G, CASR, KCNJ1, and WNK4 are key hypertension-related hub genes in ccRCC.
- These genes offer potential as biomarkers and therapeutic targets for ccRCC.
- Pseudoginsenoside-F11 and ECG show promise as ccRCC therapeutics, supporting a molecular link between hypertension and ccRCC.
