Development of a multivariable risk model integrating urinary cell DNA methylation and cell-free RNA data for the detection of significant prostate cancer

The Prostate
Shea P ConnellDaniel S Brewer

Abstract

Prostate cancer exhibits severe clinical heterogeneity and there is a critical need for clinically implementable tools able to precisely and noninvasively identify patients that can either be safely removed from treatment pathways or those requiring further follow up. Our objectives were to develop a multivariable risk prediction model through the integration of clinical, urine-derived cell-free messenger RNA (cf-RNA) and urine cell DNA methylation data capable of noninvasively detecting significant prostate cancer in biopsy naïve patients. Post-digital rectal examination urine samples previously analyzed separately for both cellular methylation and cf-RNA expression within the Movember GAP1 urine biomarker cohort were selected for a fully integrated analysis (n = 207). A robust feature selection framework, based on bootstrap resampling and permutation, was utilized to find the optimal combination of clinical and urinary markers in a random forest model, deemed ExoMeth. Out-of-bag predictions from ExoMeth were used for diagnostic evaluation in men with a clinical suspicion of prostate cancer (PSA ≥ 4 ng/mL, adverse digital rectal examination, age, or lower urinary tract symptoms). As ExoMeth risk score (range, 0-1) increased, t...Continue Reading

References

Jun 20, 2003·European Urology·Daphne HesselsJack A Schalken
Nov 14, 2006·Medical Decision Making : an International Journal of the Society for Medical Decision Making·Andrew J Vickers, Elena B Elkin
Feb 20, 2008·Neoplasia : an International Journal for Oncology Research·Scott A TomlinsArul M Chinnaiyan
May 13, 2009·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Jennifer R StarkLorelei A Mucci
Mar 19, 2011·BMC Bioinformatics·Xavier RobinMarkus Müller
Jan 21, 2014·European Urology·Stacy LoebRuth Etzioni
May 20, 2015·European Urology·Scott A TomlinsArul M Chinnaiyan
Feb 5, 2016·Contemporary Oncology Współczesna Onkologia·Pietro Pepe, Michele Pennisi
Mar 10, 2016·Nature Reviews. Urology·Jeffrey J TosoianStacy Loeb
Apr 25, 2016·European Urology·Leander Van NesteJack A Schalken
Jun 2, 2016·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Kathleen F KerrHolly Janes
Sep 15, 2016·The New England Journal of Medicine·J L DonovanUNKNOWN ProtecT Study Group*
Feb 24, 2017·Cancer Treatment Reviews·Chiara CiccareseGiampaolo Tortora
Jul 30, 2017·European Urology Focus·Bogdan-Alexandru LucaColin S Cooper
Dec 12, 2017·European Urology Focus·Geoffrey A SonnJohn T Leppert
Mar 7, 2018·JAMA : the Journal of the American Medical Association·Richard M MartinUNKNOWN CAP Trial Group
Apr 5, 2018·Cell Reports·Christopher J RickettsW Marston Linehan
Feb 26, 2019·JCO Precision Oncology·Eve O'ReillyAntoinette S Perry
May 21, 2019·BJU International·Shea P ConnellJeremy Clark
May 28, 2019·International Journal of Cancer. Journal International Du Cancer·Siri H StrandKarina D Sorensen
Jun 21, 2019·Nature Methods·Joses HoAdam Claridge-Chang

❮ Previous
Next ❯

Citations

Jun 13, 2021·Epigenetics : Official Journal of the DNA Methylation Society·Rachel M LuciaHannah Lui Park

❮ Previous
Next ❯

Methods Mentioned

BETA
biopsy
biopsies
urine volume collected

Software Mentioned

dabestr
Boruta
ExoMeth
ExoDX
NanoString
rmda
epiCaPture
pROC
R
ggplot2

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.