Detecting Neuroendocrine Prostate Cancer Using Tissue-Informed Cell-Free DNA Methylation Analysis

Neuroendocrine prostate cancer (NEPC) is a resistance phenotype known to occur in men with metastatic castration-resistant prostate adenocarcinoma (CR-PRAD). The phenotype has important clinical implications but is challenging to detect in practice. In a study, researchers developed a novel tissue-informed epigenetic approach to non-invasively detect NEPC. The findings were published in Clinical Cancer Research.

The investigators performed methylated immunoprecipitation and high-throughput sequencing (MeDIP-seq) on a training set of tumors and identified differentially methylated regions between NEPC and CR-PRAD. Based on this, they constructed a model to predict the presence of NEPC (termed NEPC Risk Score). To predict the accuracy of this model to predict NEPC, they performed MeDIP-seq on cell-free DNA (cfDNA) from two independent cohorts of men with NEPC or CR-PRAD. Overall, the study assessed 48 men (9 with NEPC and 39 with CR-PRAD).

According to the results, NEPC Risk Scores were significantly higher in men with NEPC than CR-PRAD (P = 4.3×10-7). Moreover, the model was able to discriminate between NEPC and CR-PRAD with high accuracy (area under curve = 0.96). The optimal NEPC Risk Score cut-off demonstrated 100% sensitivity and 90% specificity for detecting NEPC, according to the researchers. They concluded that, “Tissue-informed cfDNA methylation analysis is a promising approach for non-invasive detection of NEPC in men with advanced prostate cancer.”