Prostate Cancer (PCA) Is A Difficult Disease To Understand

Prostate cancer (PCa) is a difficult disease to understand. The tumor's genetic diversity increases as mutations accumulate, resulting in distinct subclones. Non-genetic intra-tumoral heterogeneity, the cellular differentiation state, and the interaction between subclonal evolution and transcriptional heterogeneity are poorly understood. The authors performed single-cell RNA sequencing on 14 untreated PCa patients in this study. They developed a comprehensive cell atlas of PCa patients and mapped developmental states onto tumor subclonal evolution. They found distinct subclones in PCa patients and then divide tumor cells into four transcriptional subtypes: EMT-like (subtype 0), luminal A-like (subtype 1), luminal B/C-like (subtype 2), and basal-like (subtype 3). These subtypes are organized hierarchically into stem cell-like and differentiated states. Surprisingly, multiple subclones within a single primary tumor have distinct preferential subtype combinations. 

Furthermore, subclones exhibit varying levels of communication with other cell types within the tumor ecosystem, which may modulate the distinct transcriptional subtypes of the subclones. Notably, they discovered that tumor cell transcriptional heterogeneity and cellular ecosystem diversity correlate with features of a poor prognosis by integrating TCGA data. Their research examines subclonal and transcriptional heterogeneity and its implications for patient prognosis.