Novel Transcriptomic Interactions Between Immune Content and Genomic Classifier Predict Lethal Outcomes in High-grade...

Area of Science:

• Oncology
• Genomics
• Immunology

Background:

• Prostate cancer (PCa) patients in grade groups 4 and 5 (GG-45) face the highest risk of lethal outcomes.
• Current genomic risk stratification methods are insufficient for GG-45 PCa prognosis and treatment selection.

Purpose of the Study:

• To assess transcriptomic interactions between immune content score (ICS) and the Decipher genomic classifier.
• To identify the most lethal subsets within GG-45 PCa using these combined biomarkers.

Main Methods:

• Utilized whole transcriptome data from 8071 tumor tissue samples (prostatectomy and biopsy).
• Derived four immunogenomic subtypes based on ICS and Decipher classifier.
• Analyzed GG-45 patient samples (n=1420) and a multivariable model (n=335).

Main Results:

• GG-45 samples showed the highest proportion of the aggressive ICS^High/Decipher^High subtype.
• The ICS^High/Decipher^High subtype was linked to increased genomic radiosensitivity.
• This subtype significantly increased the risk of distant metastasis (HR=5.41) and PCa-specific mortality (HR=10.6) compared to ICS^Low/Decipher^Low.

Conclusions:

• Novel immunogenomic subtypes reveal a synergistic interaction between ICS and Decipher.
• This interaction effectively identifies GG-45 patients with the most lethal outcomes.
• Aids in subtyping aggressive PCa patients for potential combined immune-radiotherapy.