AUA 2016: Gene Expression Analysis of Bone Metastasis and Circulating Tumor Cells from Metastatic Castrate-resistant Prostate Cancer Patients - Session Highlights

San Diego, CA USA (UroToday.com) A podium presentation in today’s Prostate Cancer: Advanced (including Drug Therapy) III session at the AUA 2016 described Gene Expression Analysis of Bone Metastasis and Circulating Tumor Cells from Metastatic Castrate-resistant Prostate Cancer Patients. Dr Michael Leviner discussed that Characterization of gene expression in bone metastasis is critical to the identification of therapeutic targets and prognostic/predictive biomarkers in metastatic castrate-resistant prostate cancer (mCRPC).

In contrast to bone marrow biopsy (BMB), which is invasive and has significant complications, circulating tumor cells (CTCs) can be obtained by a simple blood draw, and in mCRPC, CTCs likely emanate from bone metastases.

The authors sought to establish a sensitive method for gene expression analysis in BMBxs and CTCs and to explore the hypothesis that potential biomarkers present in bone lesions are mirrored in CTCs.

The authors identified areas of relatively pure prostate cancer tissue from BMB and used laser capture microdissection to isolate them. CTCs were enriched from blood using the CellSearch® platform. These 2 tissue sources were used for linear RNA amplification using an Eberwine-based procedure and obtained an antisense mRNA (aRNA). Then, the expression of 8 genes was assessed using RT-PCR. In control experiments, the efficiency of CTC isolation and linearity of RNA amplification were determined by comparing relative gene expression levels in non-amplified RNAs from large numbers of cultured PC3 cells and amplified aRNAs from small numbers of PC3 cells spiked in normal blood and recovered using the CellSearch® system.

The authors were successful in extracting RNA from even 1 CTC. There was only partial concordance between gene expression patterns in CTCs and micro dissected prostate cancer tissue from bone metastases of the same patients in 75% of the 4 cases. The authors conclude that aRNA amplification through in vitro transcription has not yet matured but could serve in the future as a useful method for gene analysis in small numbers of CTCs and tumor cells micro dissected from BMB. The data suggests that molecular analysis of CTCs might reveal gene expression patterns that might be missed by analysis of single BMB sites.

 

Presented By: Michael Leviner, MD

Written By: Miki Haifler MD. Fox Chase Cancer Center, Philadelphia, PA. at the 2016 AUA Annual Meeting - May 6 - 10, 2016 – San Diego, California, USA