Molecular subtypes and prognostic tests in prostate cancer: reducing clinical interventions and overtreatment

Date: Monday 9th December 2019
Time: 11:30
Venue: Hutchison/MRC Cancer Unit, Cambridge Biomedical Campus, room 1.8/1.9

The Cancer Genetics team at the Norwich Medical School, UEA, is an interdisciplinary team comprising a mixture of bioinformaticians, clinicians, and lab-based scientists. They have a broad interest in applying cutting-edge analytical and laboratory techniques in translational cancer based molecular studies with the aim of improving patient care, with a particular focus on prostate cancer. In this talk Daniel Brewer will describe work on two projects he is actively pursuing which he hopes will reduce overtreatment and the number of biopsies performed: a prognostic biomarker based on cell free RNA in urine and defining molecular subtypes in prostate cancer.

In the first project, post-digital rectal examination (DRE) cell free RNA expression profiles from urine (n= 535, multiple centres) were interrogated with a curated NanoString panel. A risk classifier (Prostate-Urine-Risk signatures or PUR) was developed capable of providing diagnostic information of disease status prior to biopsy, and prognostic information for men on active surveillance (AS). Application of PUR provided a net benefit over current clinical practice. We have now developed an improved technique to gather RNA from urine which avoids the need for DRE or rapid processing, making it suitable to be used as an at-home collection. We are currently validating and developing further this test in a multi-centre study. In the second project, we have successfully applied a Bayesian clustering method called Latent Process Decomposition (LPD) that takes into account the heterogeneous composition of cancer to a large range of prostate cancer transcriptome datasets. We identify a number of novel molecular subtypes including DESNT (latinDEScenduNT, they descend) which exhibit poor outcomes relative to other patients and increased risk of developing metastasis.