An 18-Gene Algorithm urine test for predicting prostate cancer metastasis and castration- resistance

Abstract

Abstract Background There is an urgent need to accurately predict the risk of distant metastasis and metastatic castration-resistant prostate cancer (mCRPC) for treatment decision-making and reducing mortality. An artificial intelliegnce machine learning screening method in combination with liquid biopsy urine test was used to develop a novel gene expression-based algorithm for predicting prostate cancer distant metastasis and mCRPC in newly diagnosed patients. Methods Random forest machine learning algorithm screening was conducted to develop and validate a gene expression-based algorithm to predict the risk of metastasis and mCRPC using liquid biopsy urine samples from the patients with distant metastasis and mCRPC collected from multi-center retrospective (n = 505) and prospective (n = 243) studies with a median follow-up period of 8 and 6 years respectively. The prognostic performance of the algorithm test was assessed using univariate/multivariate Cox regression analyses, Kaplan-Meier disease-free survival plot, and univariate/multivariate discriminant analyses. Results A novel 18-Gene Algorithm urine test was developed and validated. The algorithm showed high accuracy to predict distant metastasis with an area under the curve (AUC) of 0.96 (95% CI 0.87–1.05) and 0.98 (95% CI 0.96–1.02) in the retrospective and prospective cohort respectively. In the prospective cohort, a hazard ratio (HR) to predict metastasis-free survival was 93.8 (95% CI 29.3-300.6) (p < 0.0001). In a prospective mCRPC cohort (n = 205), the algorithm predicted mCRPC-free survival with a HR of 154.4 (95% CI 36.8-647.5) (p < 0.0001) and predicted mCRPC with AUC of 0.98 (95% CI 0.95–1.01). In contrast, currently using clinicopathological parameters, such as Gleason grade and pre-operative PSA, had much lower prognostic power. Conclusions The novel 18-Gene Algorithm is the first highly accurate and non-invasive liquid biopsy urine test to predict distant metastasis and mCRPC in newly diagnosed prostate cancer patients with the potential to improve prostate cancer treatment decision-making and reduce mortality.