Whole-Blood RNA Expression of Immunosuppressive Cell-Related Genes Is Associated With Prostate Cancer Progression

Progression to castration-resistant prostate cancer is influenced by immunosuppressive cells. Whole blood RNA profiling targeting these cells offers a minimally invasive method for prognostication and treatment stratification.

Patients scheduled to undergo prostate biopsy at Kanazawa University Hospital between July 2019 and April 2023 were prospectively enrolled. Whole blood samples were collected at the time of biopsy, and time to castration-resistant prostate cancer was analyzed based on immunosuppressive cell-related gene expression patterns.

Among the 400 patients who underwent prostate biopsy, 176 prostate cancer cases and 97 non-malignant cases were analyzed. Of the prostate cancer cases, 43 (24%) had metastatic disease. In prostate cancer patients, whole blood expression of CCR2, CCL5, CCR4, and FOXP3 was significantly elevated in metastatic cases and associated with a shorter time to castration-resistant prostate cancer. Based on the number of highly expressed genes, patients were stratified into poor (3-4 genes), intermediate (1-2 genes), and favorable (0 genes) risk groups. This classification revealed distinct progression rates, with 2-year castration-resistant prostate cancer-free survival rates of 74%, 84%, and 92% for the poor, intermediate, and favorable groups, respectively. Among metastatic patients, CCR2 was the only gene that remained significantly associated with earlier progression to castration-resistant prostate cancer (p = 0.0038).

Immune-related gene expression in peripheral blood may serve as a minimally invasive prognostic biomarker for prostate cancer progression.