SPDEF

Overview

SPDEF (SAM Pointed Domain-containing ETS Transcription Factor) is a prostate-enriched ETS family transcription factor that regulates luminal epithelial differentiation. In prostate cancer, SPDEF promotes androgen receptor (AR) signaling and luminal cell identity. Its epigenetic silencing in neuroendocrine prostate cancer (CRPC-NE) contributes to loss of AR signaling and is a feature distinguishing CRPC-NE from conventional CRPC-Adeno.

Alterations observed in the corpus

  • SPDEF promoter hypermethylation and mRNA loss detected in CRPC-NE (P < 10⁻⁹); also induced by long-term enzalutamide treatment of LNCaP cells; selected as a component of the 70-gene NEPC classifier PMID:26855148

Cancer types (linked)

  • Castration-resistant prostate cancer, neuroendocrine subtype (CRPC-NE): SPDEF silencing by promoter methylation strongly associated with neuroendocrine transdifferentiation PMID:26855148

Co-occurrence and mutual exclusivity

Therapeutic relevance

  • SPDEF silencing induced by long-term enzalutamide treatment suggests a potential epigenetic mechanism of resistance to AR-targeted therapy PMID:26855148
  • Conventional NEPC markers (CHGA, SYP, NSE, CD56) and SPDEF individually underperformed the integrated 70-gene classifier for CRPC-NE diagnosis PMID:26855148

Open questions

  • Whether SPDEF promoter methylation is reversible with EZH2 inhibitors such as GSK343 is hypothesized but not tested in patients PMID:26855148

Sources

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