Real-time clinical validation of a blood cell-free, mRNA-based GeneVerify test for screening and early diagnosis of prostate cancer.

3053 Background: Prostate cancer screening methods, including prostate-specific antigen (PSA) testing, radiological imaging, and pathological assessments, often fail to achieve reliable early detection. Despite advancements, gene-based diagnostic tests tailored for early detection of prostate cancer remain underdeveloped. To bridge this gap, we evaluated the clinical utility and diagnostic accuracy of the plasma cell-free mRNA-based GeneVerify test. This cutting-edge diagnostic approach aims to deliver faster and more precise results while avoiding the risks and complications associated with surgical biopsies. Methods: Blood samples were prospectively collected from patients suspected of prostate cancer who presented with urinary symptoms, persistently elevated PSA levels (>4 ng/mL), and PIRADS 4-5 lesions. All patients were recommended for a transperineal biopsy. Plasma cell-free RNA was isolated and analyzed for 25 prostate cancer-specific genes using the GeneVerify real-time PCR kit (Hayward, USA). The log2 fold change in gene expression for each gene was calculated, and a genetic risk score (GeneVerify Dx) was assigned to each patient. The transperineal biopsy results served as the reference standard. The diagnostic performance of the test in distinguishing between benign and cancerous cases was assessed and ROC (receiver operating characteristic) curve was plotted. Results: We tested a total of 45 subjects, comprising 35 suspected prostate cancer cases and 10 healthy controls. The median age of the cases was 66 years (range: 45–85), while the controls had a median age of 41.5 years (range: 39–47). The genetic risk score effectively differentiated prostate cancer patients from benign cases. The Area Under the Curve (AUC) was 0.83 ± 0.07 (P = 0.002; 95% CI: 0.70–0.96), demonstrating the test's strong discriminatory ability. Using a risk score cut-off value of 10, the test achieved a sensitivity of 72% and a specificity of 90%. Additionally, patients with higher Gleason grades and those experiencing chronic inflammation exhibited elevated gene expression levels and higher risk scores compared to benign subjects. Conclusions: In summary, this prospective study is the first to validate a blood cell-free RNA-based GeneVerify test for real-time screening and early detection of prostate cancer. The test exhibits high precision in identifying early-stage prostate cancer, with strong concordance to biopsy results.