Gene Expression Signature Predictive of Neuroendocrine Transformation in Prostate Adenocarcinoma

International Journal of Molecular Sciences

卷:21

Elena Jachetti¹  Caterina Peraldo-Neia²  Debora Sesia²  Francesca Guana²  Paola Ostano²  Ilaria Gregnanin²  Giovanna Chiorino²  Maurizia Mello-Grand²  Antonella Farsetti³ 

[1] Department of Research, Molecular Immunology Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, 20133 Milan, Italy;

[2] Laboratory of Cancer Genomics, Fondazione Edo ed Elvo Tempia, via Malta 3, 13900 Biella, Italy;

[3] National Research Council - Institute of Analysis, Systems and Computer Science –CNR-IASI, 00185 Rome, Italy;

关键词: neuroendocrine prostate cancer;    neuroendocrine transdifferentiation;    prostate cancer;    long non coding rnas;    estrogen signaling pathway;    predictive gene signature;   

DOI  :  10.3390/ijms21031078

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown