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Cross-Comparison Individual Patient-Level Analysis of Three Gene Expression Signatures in Localized Prostate in Over

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The 22-gene Decipher genomic classifier (GC) shows minimal correlation with the Genomic Prostate Score (GPS) and Prolaris (cell cycle progression [CCP]) signatures. These prostate cancer tests are not interchangeable and require distinct clinical guidance.

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Area of Science:

  • Oncology
  • Genomics
  • Biomarker Discovery

Background:

  • The 22-gene Decipher genomic classifier (GC) is a validated tool for localized prostate cancer (PCa) treatment decisions.
  • The correlation and evidence strength of other commercial signatures like Genomic Prostate Score (GPS) and Prolaris (cell cycle progression [CCP]) with 22-gene GC are not well-established.

Purpose of the Study:

  • To assess the per-patient correlation between the 22-gene GC, GPS, and CCP signatures in a large cohort of prostate cancer patients.
  • To determine if GPS and CCP correlate sufficiently with 22-gene GC to explain differences in evidence strength for treatment decision-making.

Main Methods:

  • Whole-transcriptome gene expression microarray analysis of primary PCa biopsy samples from 50,881 patients.
  • Calculation of 22-gene GC scores and retraining of GPS and CCP signatures to predict metastasis for endpoint harmonization.
  • Univariable and multivariable linear regression analyses, adjusting for clinical factors (age, grade group, PSA, T stage), to assess correlations (Pearson) and variance explained (R²).

Main Results:

  • GPS-derived and CCP-derived models showed poor goodness-of-fit to 22-gene GC (R² = 0.36 and 0.32).
  • Multivariable analysis confirmed minimal to moderate correlation, with approximately 60% of 22-gene GC variation remaining unexplained by clinical factors.
  • GPS and CCP accounted for only 24.7% and 22.7% of variance, respectively, with additional minor contributions from Gleason score.

Conclusions:

  • Correlation between 22-gene GC and GPS-derived or CCP-derived signatures is minimal to moderate.
  • The tested genomic classifiers are not interchangeable for prostate cancer treatment decision-making.
  • Clinical use of each signature should be guided by its specific supporting evidence and validation data.