Development and evaluation of a "molecular biopsy" for improved diagnosis of prostate cancer

• Main Author: Nair, Sabarinath Balachandran
• Format: Dissertation
• Language: English
• Published: St George's, University of London 2013

Prostate cancer is the most commonly diagnosed cancer in men in United Kingdom. Current diagnosis involves measurement of serum PSA levels and prostate biopsy. However, these tests can give false positive or negative results. Furthermore, they do not indicate disease staging, the behaviour and development of the cancer and hence do not lend to optimal management. Using blood samples, quantitative, real-time RT-PCR (LightCycler™) was used to evaluate molecular markers for inclusion in an alternative minimally invasive diagnostic and prognostic test. Expression levels of Clusterin, Caveolin-1 (Cav-1), E-cadherin (ECAD), Alpha-Methylacyl-CoenzymeA Racemase (AMACR), Enhance of zeste homologue 2 (EZH2) and Matrix metalloproteinases 2 and 24 (MMP2, MMP24) were measured in patient groups and correlated with known clinical details collected on a prostate cancer database. Normal males and patients with negative biopsy results were used as control groups. GAPDH was chosen as the housekeeping gene to normalize gene expression levels. Results and subsequent statistical analysis indicate that Clusterin, Cav-1, and ECAD are potentially strong markers for prostate cancer diagnosis and staging of the disease, and therefore in patient management. The strength of these markers can be increased by combining the results with other similarly evaluated markers. In this way, a combination of diagnostically and prognostically strong markers may be identified forming a panel of biomarkers for inclusion in a potential test. The development of further products now allows transportation of blood at ambient temperature with guaranteed mRNA stability. This will allow blood samples to be taken in a local surgery and transported to a routine laboratory for testing. This would help encourage men to seek prostate disease screening, enabling early diagnosis and intervention while avoiding unnecessary prostate biopsies and treatment.