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Title: Exosomal RNA as a source of urine biomarkers for prostate cancer
Author: Yazbek Hanna, Marcelino
ISNI:       0000 0004 7231 5976
Awarding Body: University of East Anglia
Current Institution: University of East Anglia
Date of Award: 2017
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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.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available