Molecular Hallmarks of Multiparametric Magnetic Resonance Imaging Visibility in Prostate Cancer

Kathleen E Houlahan; Amirali Salmasi; Taylor Y Sadun; Aydin Pooli; Ely R Felker; Julie Livingstone; Vincent Huang; Steven S Raman; Preeti Ahuja; Anthony E Sisk Jr; Paul C Boutros; Robert E Reiter

doi:10.1016/j.eururo.2018.12.036

Molecular Hallmarks of Multiparametric Magnetic Resonance Imaging Visibility in Prostate Cancer

Eur Urol. 2019 Jul;76(1):18-23. doi: 10.1016/j.eururo.2018.12.036. Epub 2019 Jan 24.

Authors

Affiliations

¹ Ontario Institute for Cancer Research, Toronto, Canada; Department of Medical Biophysics, University of Toronto, Toronto, Canada; Vector Institute, Toronto, Canada.
² Department of Urology, David Geffen School of Medicine, University of California, Los Angeles, CA, USA.
³ Department of Radiology, David Geffen School of Medicine, University of California, Los Angeles, CA, USA.
⁴ Ontario Institute for Cancer Research, Toronto, Canada.
⁵ Department of Pathology, David Geffen School of Medicine, University of California, Los Angeles, CA, USA.
⁶ Ontario Institute for Cancer Research, Toronto, Canada; Department of Medical Biophysics, University of Toronto, Toronto, Canada; Vector Institute, Toronto, Canada; Department of Urology, David Geffen School of Medicine, University of California, Los Angeles, CA, USA; Department of Pharmacology and Toxicology, University of Toronto, Toronto, Canada; Department of Human Genetics, University of California, Los Angeles, CA, USA; Jonsson Comprehensive Cancer Center, David Geffen School of Medicine, University of California, Los Angeles, CA, USA; Institute for Precision Health, University of California, Los Angeles, CA, USA; UCLA Department of Human Genetics, 10833 Le Conte Avenue, Los Angeles, CA 90095. Electronic address: Paul.Boutros@oicr.on.ca.
⁷ Department of Urology, David Geffen School of Medicine, University of California, Los Angeles, CA, USA; Jonsson Comprehensive Cancer Center, David Geffen School of Medicine, University of California, Los Angeles, CA, USA; Institute of Urologic Oncology, University of California, Los Angeles, CA, USA; Department of Urology, David Geffen School of Medicine, 300 Stein Plaza, Los Angeles, CA 90095, USA. Electronic address: RReiter@mednet.ucla.edu.

Abstract

Multiparametric magnetic resonance imaging (mpMRI) has transformed the management of localized prostate cancer by improving identification of clinically significant disease at diagnosis. Approximately 20% of primary prostate tumors are invisible to mpMRI, and we hypothesize that this invisibility reflects fundamental molecular properties of the tumor. We therefore profiled the genomes and transcriptomes of 40 International Society of Urological Pathology grade 2 tumors: 20 mpMRI-invisible (Prostate Imaging-Reporting and Data System [PI-RADS] v2 <3) and 20 mpMRI-visible (PI-RADS v2 5) tumors. mpMRI-visible tumors were enriched in hallmarks of nimbosus, an aggressive pathological, molecular, and microenvironmental phenomenon in prostate cancer. These hallmarks included genomes with increased mutation density, a higher prevalence of intraductal carcinoma/cribriform architecture pathology, and altered abundance of 102 transcripts, including overexpression of noncoding RNAs such as SCHLAP1. Multiple small nucleolar RNAs (snoRNAs) were identified, and a snoRNA signature synergized with nimbosus hallmarks to discriminate visible from invisible tumors. These data suggest a confluence of aggressive molecular and microenvironmental phenomena underlie mpMRI visibility of localized prostate cancer. PATIENT SUMMARY: We examined the correlation between tumor biology and magnetic resonance imaging (MRI) visibility in a group of patients with low- intermediate-risk prostate cancer. We observed that MRI findings are associated with biological features of aggressive prostate cancer.

Keywords: Multiparametric magnetic resonance imaging visibility; Nimbosus; Prostate cancer; Radiogenomics; Transcriptomics.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Aged
Gene Dosage
Gene Expression Profiling
Genome
Humans
Male
Middle Aged
Multiparametric Magnetic Resonance Imaging*
Prostatic Neoplasms / diagnostic imaging*
Prostatic Neoplasms / genetics*
Prostatic Neoplasms / metabolism
Prostatic Neoplasms / pathology
RNA, Long Noncoding / genetics*
RNA, Long Noncoding / metabolism
RNA, Messenger / metabolism*
RNA, Small Nuclear / metabolism*
Transcriptome
Tumor Burden
Tumor Microenvironment

Substances

RNA, Long Noncoding
RNA, Messenger
RNA, Small Nuclear
SChLAP1 long noncoding RNA

Grants and funding

P50 CA092131/CA/NCI NIH HHS/United States