Alpha Omega Alpha Honor Medical Society

2012 Research Abstract

The Novel Use of Urinary Exosomes to Examine Survivin Expression in Castration Resistant Prostate Cancer

Investigators: James Lin, Anna Scott, Piruz Motamedinia, Guillermo Salazar, Kendall Bate, Michael Lipsky, Neda Sadeghi, Wayne D. Comper, James M. McKiernan, Daniel P. Petrylak, & Leileata M. Russo

Mentor: Daniel P. Petrylak, MD, Columbia University College of Physicians and Surgeons

Introduction and Objective: Given the numerous new agents for the treatment of patients with castration resistant prostate cancer (CRPC), identification of biological markers is essential to predicting response and providing a rationale for sequencing treatments. Microvesicles, including exosomes, are small lipid bilayer vesicles released from all cells into bodily fluids. Exosomes, which carry high integrity RNA from their parent cells, can be used to reliably interrogate the transcriptional profile of various organs in a non-invasive manner. Using urinary exosomes we examined Survivin expression, an inhibitor of apoptosis implicated in hormone independent tumor growth, in different disease states of men with advanced prostate cancer.

Methods: Following IRB approval and obtaining informed consent, urine samples were collected prior to a digital rectal exam from 4 groups of patients: radical prostatectomy with no evidence of disease (RP-NED, n=37) or alive with disease (RP-AWD, n=22), and ablative therapy (external radiation therapy or cryotherapy) with no evidence of disease (ABL-NED, n=13) or alive with disease (ABL-AWD, n=14). These patients were further categorized as CRPC and non-CRPC for the RP-AWD (n=11 & n=11) and ABL-AWD (n=8 & n=6) groups, respectively. Urinary exosomal mRNA was isolated and GAPDH and Survivin were analyzed via RT-qPCR. To compare expression levels, genes were standardized to GAPDH and relative quantitation (RQ) was calculated using the DataAssist program (v.2.0).

Results: Survivin expression was significantly higher in the RP-AWD group compared to the RP-NED group (RQ 3.63, p=0.03). A similar trend was also observed for patients with ablation therapy as their primary treatment (RQ 3.23, p=0.057). When stratified into CRPC and non-CRPC, increased Survivin expression was associated with castration resistance for RP-NED versus RP-AWD CRPC (p=0.0422) and ABL-NED versus ABL-AWD CRPC (P=0.0291). Additionally, Survivin expression was significantly higher in the ABL-AWD patients with CRPC versus those with non-CRPC (RQ 6.30, p=0.027).

Conclusions: Using urinary exosomal RNA, Survivin levels are elevated in men with CRPC. This non-invasive assay may be utilized to follow prostate cancer patients over time and monitor gene expression during treatment, giving greater insight into the molecular changes that occur during disease progression and response to treatment.

Updated on August 6, 2013.

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