Abstract

Metastasis is the leading cause of death in patients diagnosed with prostate cancer (PCa), underscoring the need for reliable prediction tools to forecast the risk of metastasis at an early stage. Here, we utilize the gene expression profiles of 1,000 unique primary tumors from patients with localized PCa to develop a gene signature capable of predicting metastasis. Our signature, termed Meta-Score, comprises forty-five genes that can accurately distinguish primary tumor with high propensity for metastasis across different patient cohorts. Notably, Meta-Score maintained its robust predictive performance in an internal validation cohort of comprising primary tumor samples from 239 patients. In addition to its robust predictive performance, Meta-Score demonstrates a significant association with survival, independent of Gleason score in two independent patient cohorts, underscoring its prognostic utility. Taken together, Meta-Score is a robust risk-stratification tool that can be leveraged to identify patients at high-risk of metastasis and unfavorable survival using their primary tumor gene expression profiles.

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