Abstract 5685: An evaluation of DNA and RNA based blood biomarkers in prostate cancer

• Published in: Cancer research (Chicago, Ill.) Ill.), 2017-07, Vol.77 (13_Supplement), p.5685-5685
• Main Authors: Antonello, Jenny, Chudziak, Jakub, Redfern, Alan, Foy, Victoria, Srivastava, Shambhavi, Syed, Adnan, Burt, Deborah, Ayub, Mahmood, Kilerci, Bedirhan, Parry, Marina, Marais, Richard, Baena, Esther, Miller, Crispin, Rothwell, Dominic, Clarke, Noel, Dive, Caroline, Brady, Ged
• Format: Article
• Language: English
• ISSN: 0008-5472; 1538-7445
• DOI: 10.1158/1538-7445.AM2017-5685

Background: Prostate cancer (CaP) is the second-leading cause of male cancer-related mortality in Western societies. Localised prostate cancer (Loc-CaP) can be classified into low-, intermediate-, or high-risk groups. Active surveillance is recommended for low-risk patients, whereas radiotherapy or surgery is often indicated in intermediate- and high-risk patients, with possible intensification using hormone therapy treatment. Despite advances in radiation delivery and surgery, ~20% of patients will not be cured with local treatment and require androgen deprivation therapy (ADT). The majority will develop resistance to ADT resulting in castration resistant prostate cancer (CRPC) with poor prognosis and increased risk of metastatic disease (mCRPC). Biomarkers are being developed based on tumour biopsies which may help stratify patients and allow more effective treatment. However tumour biopsies are invasive, demanding for patients and surgeons as well as challenging for longitudinal sampling. Here we evaluate a range of blood biomarkers suitable for longitudinal sampling including circulating tumour cells (CTCs), circulating tumour DNA (ctDNA) and Tumour educated platelet mRNA (TEP-RNA). Methods: A blood sampling, processing and banking pipeline has been established for CaP patients providing ctDNA, enriched and single CTCs as well as TEP-RNA. Following ctDNA isolation, next generation sequencing (NGS) libraries are prepared to generate copy number alteration (CNA) data and mutation profiles. CTCs are enriched using both the epitope independent Parsortix (P-CTC) (Chudziak J. et al, 2016) and the epitope dependent (EPCAM and KRT19) CellSearch (CS-CTC) platforms. Genomic analysis of CTCs is carried out by NGS of whole genome amplified (WGA) single and pooled CTCs. CTC and TEP-RNA mRNA profiles are established using both the Fluidigm RT qPCR (Fluidigm Biomark™ HD system) and RNA-Seq. Results: Over 160 Loc-CaP and 100 mCRPC blood samples have been collected, processed and banked. In keeping with published data 53% of the 100 mCRPC patients have &gt5 CS-CTCs (a poor prognostic indicator) compared to 100% of Loc-CaP having 1000 fold enrichment of epithelial mRNAs post Parsortix CTC enrichment indicate an equivalent enrichment of the “spiked in” cells. Similar epithelial mRNA enrichment was seen in 3/5 mCRPC clinical samples tested. Tumour associated CNA changes were clearly detected in at least 15 of the 1st 22 m