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Validation of a 15-Gene Prognostic Signature in Metastatic Clear Cell Renal Cell Carcinoma

  • 0Department of Urology, Michigan Medicine, Ann Arbor, MI.
Jco Precision Oncology +

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June 6, 2025

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June 6, 2025

View abstract on PubMed

Summary

This summary is machine-generated.

The 15-gene score (15G score) effectively predicts outcomes in metastatic clear cell renal cell carcinoma (ccRCC). A high 15G score indicates worse progression-free survival and overall survival across various systemic therapies.

Area Of Science

  • Oncology
  • Genomics
  • Translational Research

Background

  • A 15-gene prognostic signature (15G score) was previously validated for localized clear cell renal cell carcinoma (ccRCC).
  • The 15G score differentiates aggressive from indolent ccRCC, showing potential for broader application.

Purpose Of The Study

  • To evaluate the prognostic performance of the 15G score in patients with metastatic ccRCC.
  • To assess the 15G score's association with progression-free survival (PFS) and overall survival (OS) across different systemic therapies.

Main Methods

  • Analysis of 2,121 patients from four major metastatic ccRCC trial data sets (IMmotion 151, IMmotion 150, Javelin Renal 101, Checkmate 009/010/025).
  • Patients were classified into 15G score high or low groups using RNA-sequencing.
  • Progression-free survival (PFS) and overall survival (OS) were analyzed using Cox proportional hazards models, with and without controlling for MSKCC risk group.

Main Results

  • A high 15G score was significantly associated with worse PFS in four of six treatment groups, including atezolizumab plus bevacizumab, sunitinib, atezolizumab, and everolimus.
  • The 15G score remained an independent predictor of worse PFS in multivariable analyses for atezolizumab plus bevacizumab, sunitinib, and everolimus.
  • A high 15G score was also associated with worse OS, notably in the everolimus group.

Conclusions

  • The 15G score demonstrates independent prognostic value in metastatic ccRCC.
  • This signature can inform prognosis across diverse systemic therapy regimens in metastatic ccRCC patients.