Single-cell transcriptomics redefines focal neuroendocrine differentiation as a distinct prostate cancer pathology

Abstract

Neuroendocrine prostate cancer (NEPC) tumours are classified by pathology into several distinct subtypes. Gene expression profiling has revealed transcriptional heterogeneity across NEPC, but this is rarely considered in the context of variation between pathologies. Diagnosis typically relies on immunohistochemical markers (CHGA, SYP, NCAM1) and genomic alterations in RB1, PTEN and TP53. We hypothesized that NEPC pathologies have unique transcriptional features. Single-cell RNA sequencing of 18 632 tumour cells from nine patient-derived xenograft models representing five pathologies (small-cell and large-cell neuroendocrine carcinomas, focal neuroendocrine differentiation (Focal NED), low-gr..