Exosomal RNA as a source of urine biomarkers for prostate cancer

Yazbek Hanna, Marcelino (2017) Exosomal RNA as a source of urine biomarkers for prostate cancer. Doctoral thesis, University of East Anglia.

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Abstract

Introduction
In this study we exploited the recent development of methods that have enabled the analysis of
RNA present in urine exosomes of prostate cancer patients. We report RNA expression patterns
that contain diagnostic and prognostic information for prostate cancer, and association with
response to hormone treatment.
Methods
First catch urine following digital rectal examination were collected from 662 men. 3 groups of
patients were used: Low, Intermediate, and High-risk according to NICE stratification criteria, and
two control groups: benign and advanced disease. 50-gene transcript expression analysis using
NanoString technology was performed on 192 samples. Exosomal RNA Next-Generation
Sequencing was performed on 18 samples for novel biomarker discovery.
Results
Expression analysis showed that PCa-specific transcripts such as TMPRSS2/ERG fusion
transcripts were identifiable in exosomes from PCa urine samples. LPD analysis highlighted
expression levels of 15 transcripts with diagnostic potential (significantly up-regulated in cancer
samples in comparison to benign control) and 17 transcripts with prognostic potential
(differentialy expressed in high risk and advanced disease in comparison to lower grade disease).
I also report two gene transcripts (SERPINB5/Maspin, HPRT) that were significantly
differentially expressed in patients who failed to respond to hormone deprivation therapy for high
risk/metastatic disease. Three genes (STEAP4, ARexons4_8 and NAALADL2) were significantly
differentially expressed in patients who relapsed within 12 months of hormone treatment
initiation.
Next-Generation Sequencing of twenty samples identified 45 genes to be significantly
differentially expressed between non-cancer and cancer samples (28 were up regulated and 17
down regulated). 33 out of the 45 genes showed a significant linear trend in association with
cancer risk.
Conclusions
Urine Exosomal RNA contains PCa specific transcripts. Gene expression analysis and Next
Generation Sequencing identified genes that are significantly differentially expressed between
cancer and non-cancer cases as well as prognostic genes and genes that can predict response to
hormone treatment

Item Type: Thesis (Doctoral)
Faculty \ School: Faculty of Medicine and Health Sciences > Norwich Medical School
Depositing User: Stacey Armes
Date Deposited: 22 Mar 2018 14:43
Last Modified: 22 Mar 2018 14:43
URI: https://ueaeprints.uea.ac.uk/id/eprint/66563
DOI:

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