Intermediate-risk and high-risk localized prostate cancer are treatable, but metastases (in ~30% of patients) often lead to death. Immunotherapy shows promise for survival, but many patients do not respond, highlighting the need for biomarkers to predict metastases and treatment response.

In an article published in Scientific Reports, a novel indicator based on cell death was developed to predict metastases, biochemical recurrence (BCR) and immunotherapy response in prostate cancer. Prompted by the rationale that cell death pathways are crucial in metastases development, the authors used prostate adenocarcinoma data in The Cancer Genome Atlas (TCGA) to develop an eight-gene signature referred to as programmed cell death score (PCDS) based on differentially expressed genes associated with various programmed cell death mechanisms. Analysis of data from TCGA plus two validation cohorts showed that high PCDS is associated with aggressive tumour features, including increased metastases, T stage, grade and BCR, whereas low PCDS is associated with enhanced response to immunotherapy. A random forest analysis showed that, among the eight PCDS genes, the prostaglandin synthase PTGDS had the greatest influence on prostate cancer metastases. PTGDS expression was lower in metastatic versus non-metastatic prostate cancer tissue samples, and overexpression of PTGDS in prostate cancer cell lines reduced tumour cell migration, invasion and proliferation.