Transcriptomics

Dataset Information

2

Identification of DEK as a potential therapeutic target for Neuroendocrine prostate cancer


ABSTRACT: Introduction: Neuroendocrine prostate cancer (NEPC) is an aggressive subtype of prostate cancer, exhibiting rapid progression and is unresponsive to hormone therapy. Reliable prognostic assays and more effective treatments are critically required. However, the research of NEPC has been hampered by a lack of clinically relevant in vivo models. Recently, we successfully developed a first-in-field patient tissue-derived xenograft model of complete neuroendocrine transdifferentiation from prostate adenocarcinoma. By comparing gene expression profiles of the parental adenocarcinoma line (LTL331) and the NEPC subline (LTL331R), we identified DEK, a gene not previously reported in prostate cancer, as a potential biomarker and target for NEPC. Methods: DEK protein expression in patient tissue-derived xenograft models and clinical samples was assessed by immunohistochemistry. The function of DEK was determined by siRNA-induced reduction of DEK expression in PC-3 cells, a cell line with NEPC characteristics, followed by functional assays and gene expression profiling analysis. Results: Elevated DEK protein expression was observed in all clinical NEPC cases, which is distinct from their benign counterparts (0%), hormonal naïve prostate cancer (2.45%) and castration resistant prostate cancer (29.55%). Increased DEK expression is an independent clinical risk factor and is associated with shorter disease free survival in hormonal naïve prostate cancer patients. Reduction of DEK expression in PC-3 cells led to a marked reduction in cell proliferation, cell migration and invasion. Conclusions: The results suggest that DEK may play an important role in the progression of prostate cancer, especially NEPC and provide a potential biomarker to aid risk stratification of prostate cancer and a novel therapeutic target for treating NEPC. The function of DEK was determined by siRNA-induced reduction of DEK expression in PC-3 cells, a cell line with NEPC characteristics, followed by functional assays and gene expression profiling analysis.

ORGANISM(S): Homo sapiens  

SUBMITTER: Dong Lin   Sonal Brahmbhatt  Shawn Anderson  Anne Haegert  Alexander W Wyatt  Shawn A Anderson 

PROVIDER: E-GEOD-61214 | ArrayExpress | 2015-01-15

SECONDARY ACCESSION(S): GSE61214PRJNA260520

REPOSITORIES: GEO, ArrayExpress

Similar Datasets

2013-01-12 | E-GEOD-41188 | ArrayExpress
2013-01-12 | E-GEOD-41192 | ArrayExpress
| GSE99381 | GEO
| GSE28219 | GEO
2013-01-04 | E-GEOD-28219 | ArrayExpress
| GSE74245 | GEO
2017-08-30 | PXD006252 | Pride
2018-06-22 | GSE112786 | GEO
2019-05-24 | PXD010611 | Pride
2015-01-21 | E-GEOD-63539 | ArrayExpress