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Title: The role of FGF7 in castration resistant prostate cancer.
Epworth Authors: Kurganovs, Natalie
Howard, Nicholas
Bugeja, Patricia
Kerger, Michael
Dundee, Philip
Grummet, Jeremy
Peters, Justin
Costello, Anthony
Hovens, Christopher
Corcoran, Niall
Ruljancich, Paul
Parante, P.
Other Authors: Cmero, Marek
Clarke, David
Pederson, Ryan
Ryan, Andrew
Keywords: Castration Resistant Prostate Cancer
Cell Proliferation
Epithelial Mesenchymal Transition
Real Time Polymerase Chain Reaction
RNA Sequence
Single Nucleotide Polymorphism
Whole Genome Sequencing
Keratinocyte Growth Factor
Prostate Cancer
Radical Prostactomy
Fibroblast Growth Factor 2
Illumina HiSeq
Illumina HiTenX
Cell Lines
Cells Metabolism
MTT Assay
Single Nucleotide Variants
Copy Number Variations
Treatment Outcomes
Castrate Environment
Australian Prostate Cancer Research Centre Epworth HealthCare, Victoria, Australia
Eastern Health and Epworth Eastern, Box Hill, VIC, Australia
UroRenal, Vascular Clinical Institute, Epworth HealthCare, Victoria, Australia
Issue Date: Aug-2017
Citation: BJU International. 18th Asia-Pacific Prostate Cancer Conference (APCC). 2017 Aug 28; 120(S1): Poster 052: pp 22-23
Conference Name: BJU International. 18th Asia-Pacific Prostate Cancer Conference (APCC), 30 Aug – 2 Sep 2017.
Conference Location: Australia
Abstract: OBJECTIVE: To investigate the development of castration resistant prostate cancer, and the role FGF7 has in enabling these cells to survive. METHODS: A neo adjuvant trial consisting of a “super-castration” treatment with bicalutamide, abiraterone and degarelix treatment for a period of 6 months prior to radical prostactomy was conducted. DNA from 7 pre (formalin fixed paraffin bedded (FFPE)), 20 post (11 FFPE, 9 fresh frozen) and 14 germline (whole blood) samples were used for whole genome sequencing (WGS). Tissue was sequenced at 30X and blood at 15X depth on the Illumina HiTenX. RNA from 6 fresh frozen post treatment samples, and 8 matched hormone naïve samples were used to construct a RNA-Seq library and sequenced at a length of 150 bp using paired end chemistry on an Illumina HiSeq. To validate the findings from the RNA-Sequencing data, LnCaP and LaPC4 cell lines were treated with FGF7, bFGF, TGFβ, and LIF, and the cells proliferation and metabolism was measured using MTT assay. The effect of these proteins on the expression of other genes of interested was measured using qPCR. RESULTS: Although we have found through WGS that there is an increase in single nucleotide variants (SNVs), and copy number variations (CNVs) in post samples as compared to germline and pre samples in some patients, this increase is not observed in other patients with a similar response to treatment. Preliminary RNA-Seq data has detected an epithelial to mesenchymal and a basal cell signature. It has also shown an increased expression in FGF7, and preliminary validation in cell lines treated with FGF7 indicates that it plays a role in the survival of cells when they are in a castrate environment, in addition to altering the expression of genes involved in the epithelial to mesenchymal transition, as well as other genes of interest which were found to have an altered expression in the super castration cohort. CONCLUSIONS: Our results indicate that the development of castration resistant prostate cancer may be due to FGF7 enabling the survival of cells in the presence of a castrate environment.
DOI: 10.1111/bju.13943
Type: Conference Poster
Affiliated Organisations: Royal Melbourne Hospital, Parkville, VIC, Australia
University of Melbourne, Parkville, VIC, Australia
Walter and Eliza Hall Institute, Parkville, VIC, Australia
Alfred Hospital, Prahran, VIC, Australia
Monash University, Clayton, VIC, Australia
TissuPath Specialist Pathology Services, Mt Waverly, VIC, Australia
Type of Clinical Study or Trial: Controlled Clinical Trial
Appears in Collections:Cancer Services
Epworth Prostate Centre

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