Gene Expression Signature Predictive of Neuroendocrine Transformation in Prostate Adenocarcinoma.

Paola Ostano, Maurizia Mello-Grand, Debora Sesia, Ilaria Gregnanin, Caterina Peraldo-Neia, Francesca Guana, Elena Jachetti, Antonella Farsetti, Giovanna Chiorino

Research output: Contribution to journalArticlepeer-review

Abstract

Neuroendocrine prostate cancer (NEPC) can arise de novo, but much more commonly occurs as a consequence of a selective pressure from androgen deprivation therapy or androgen receptor antagonists used for prostate cancer (PCa) treatment. The process is known as neuroendocrine transdifferentiation. There is little molecular characterization of NEPCs and consequently there is no standard treatment for this kind of tumors, characterized by highly metastases rates and poor survival. For this purpose, we profiled 54 PCa samples with more than 10-years follow-up for gene and miRNA expression. We divided samples into two groups (NE-like vs. AdenoPCa), according to their clinical and molecular features. NE-like tumors were characterized by a neuroendocrine fingerprint made of known neuroendocrine markers and novel molecules, including long non-coding RNAs and components of the estrogen receptor signaling. A gene expression signature able to predict NEPC was built and tested on independently published datasets. This study identified molecular features (protein-coding, long non-coding, and microRNAs), at the time of surgery, that may anticipate the NE transformation process of prostate adenocarcinoma. Our results may contribute to improving the diagnosis and treatment of this subgroup of tumors for which traditional therapy regimens do not show beneficial effects.
Original languageEnglish
JournalInternational Journal of Molecular Sciences
Volume21
Issue number3
DOIs
Publication statusPublished - Feb 1 2020

Keywords

  • Humans
  • Male
  • Middle Aged
  • prostate cancer
  • Aged
  • Signal Transduction
  • estrogen signaling pathway
  • long non coding RNAs
  • neuroendocrine prostate cancer
  • neuroendocrine transdifferentiation
  • predictive gene signature
  • Prostate/pathology
  • Gene Expression Regulation
  • Neoplastic/genetics
  • Estrogens/metabolism
  • Adenocarcinoma/drug therapy/*genetics
  • Androgen Receptor Antagonists/adverse effects/therapeutic use
  • Androgens/metabolism
  • Carcinoma
  • Neuroendocrine/drug therapy/*genetics
  • Cell Transdifferentiation/physiology
  • Estrogen Receptor alpha/metabolism
  • MicroRNAs/*genetics
  • Prostatic Neoplasms/drug therapy/*genetics
  • Receptors
  • Androgen/metabolism
  • RNA
  • Long Noncoding/*genetics

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