Single-cell transcriptional regulation and genetic evolution of neuroendocrine prostate cancer
Ziwei Wang, Tao Wang, Danni Hong, Baijun Dong, Yan Wang, Huaqiang Huang, Wenhui Zhang, Bijun Lian, Boyao Ji, Haoqing Shi, Min Qu, Xu Gao, Daofeng Li, Colin C. Collins, Gong‐Hong Wei, Chuanliang Xu, Hyung Joo Lee, Jialiang Huang, Jing Li
Abstract
-differentiation. New marker genes we identified may be used for clinical diagnosis. Second, integrative analyses combining expression and subclonal architecture revealed different paths by which NEPC diverges from the original ADPC, either directly from treatment-naïve tumor cells or from specific intermediate states of treatment-resistance. Third, we inferred a hierarchical transcription factor (TF) network underlying the progression, which involves constitutive regulation by ASCL1, FOXA2, and selective regulation by NKX2-2, POU3F2, and SOX2. Together, these results defined the complex expression profiles and advanced our understanding of the genetic and transcriptomic mechanisms leading to NEPC differentiation.