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Senescence-associated miRNAs predict survival and modulate the tumor immune microenvironment via SPOCK1 targeting in clear cell renal cell carcinoma

  • 0Institute of Urology, Peking University First Hospital, Beijing, China.
Urologic Oncology +

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September 17, 2025

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September 17, 2025

View abstract on PubMed

Summary

This summary is machine-generated.

This study identifies a signature of senescence-associated microRNAs (CS-miRNAs) that predicts outcomes in clear cell renal cell carcinoma (ccRCC). This CS-miRNA score offers potential for personalized immunotherapy strategies in ccRCC patients.

Area Of Science

  • Oncology
  • Genomics
  • Immunology

Background

  • Clear cell renal cell carcinoma (ccRCC) is an aggressive malignancy where cellular senescence influences tumorigenesis and the immune microenvironment.
  • MicroRNAs (miRNAs) are key regulators of tumor metabolism and behavior; identifying senescence-associated miRNA (CS-miRNA) signatures is crucial for ccRCC prognosis and treatment.
  • Understanding the role of CS-miRNAs can lead to improved therapeutic strategies for ccRCC.

Purpose Of The Study

  • To develop and validate a CS-miRNA-based scoring system (CS-miRNAs-Score) for ccRCC.
  • To evaluate the association of the CS-miRNAs-Score with clinical, immunological, and mutational characteristics of ccRCC.
  • To identify novel prognostic biomarkers and therapeutic targets in ccRCC.

Main Methods

  • Multiomics analysis of 616 ccRCC samples from the TCGA-KIRC dataset.
  • Development of a CS-miRNAs-Score using machine learning, validated with external miRNA-seq data.
  • Stratification of patients into distinct clusters based on CS-miRNA expression profiles.

Main Results

  • The 10-miRNA CS-miRNAs-Score significantly correlated with overall survival, immune/stromal scores, and immune checkpoint expression.
  • The score predicted response to immunotherapy.
  • hsa-miR-130a-3p was identified as a tumor suppressor, directly inhibiting the oncogene SPOCK1 in ccRCC.

Conclusions

  • Senescence-associated miRNAs hold significant prognostic and therapeutic value in ccRCC.
  • The CS-miRNAs-Score serves as a novel biomarker for ccRCC.
  • These findings provide potential targets for developing personalized immunotherapy for ccRCC.

Keywords:

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