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Ding et al. J Transl Genet Genom 2021;5:50-61 Journal of Translational
DOI: 10.20517/jtgg.2021.01 Genetics and Genomics

Original Article Open Access

Prostate cancer in young men represents a distinct
clinical phenotype: gene expression signature to

predict early metastases

Yuan C. Ding , Huiqing Wu , Elai Davicioni , R. Jeffrey Karnes , Eric A. Klein , Robert B. Den , Linda
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5
4
3
2
1
Steele , Susan L. Neuhausen 1
1
1 Department of Population Sciences, Beckman Research Institute of City of Hope, Duarte, California, CA 91010, USA.
2 Department of Pathology, City of Hope Medical Center, Duarte, California, CA 91010, USA.
3 GenomeDX Biosciences, Vancouver, British Columbia V6B 1B8, Canada.
4 Department of Urology, Mayo Clinic, Rochester, Minnesota, MN 55905, USA.
5 Glickman Urological and Kidney Institute, Cleveland Clinic, Ohio, OH 44195, USA.
6 Department of Radiation Oncology, Thomas Jefferson University, Philadelphia, Pennsylvania, PA 19044, USA.
Correspondence to: Prof. Susan L. Neuhausen, Department of Population Sciences, Beckman Research Institute of City of Hope,
1500 E Duarte Road, Duarte, CA 91010, USA. E-mail: sneuhausen@coh.org
How to cite this article: Ding YC, Wu H, Davicioni E, Karnes RJ, Klein EA, Den RB, Steele L, Neuhausen SL. Prostate cancer in
young men represents a distinct clinical phenotype: gene expression signature to predict early metastases. J Transl Genet Genom
2021;5:50-61. http://dx.doi.org/10.20517/jtgg.2021.01
Received: 3 Jan 2021 First Decision: 27 Jan 2021 Revised: 2 Feb 2021 Accepted: 18 Feb 2021 Available online: 9 Mar 2021

Academic Editor: Sanjay Gupta Copy Editor: Yue-Yue Zhang Production Editor: Yue-Yue Zhang

Abstract
Aim: Several genomic signatures are available to predict Prostate Cancer (CaP) outcomes based on gene
expression in prostate tissue. However, no signature was tailored to predict aggressive CaP in younger men. We
attempted to develop a gene signature to predict the development of metastatic CaP in young men.

Methods: We measured genome-wide gene expression for 119 tumor and matched benign tissues from
prostatectomies of men diagnosed at ≤ 50 years and > 70 years and identified age-related differentially expressed
genes (DEGs) for tissue type and Gleason score. Age-related DEGs were selected using the improved Prediction
Analysis of Microarray method (iPAM) to construct and validate a classifier to predict metastasis using gene
expression data from 1,232 prostatectomies. Accuracy in predicting early metastasis was quantified by the area
under the curve (AUC) of receiver operating characteristic (ROC), and abundance of immune cells in the tissue
microenvironment was estimated using gene expression data.

Results: Thirty-six age-related DEGs were selected for the iPAM classifier. The AUC of five-year survival ROC
for the iPAM classifier was 0.87 (95%CI: 0.78-0.94) in young (≤ 55 years), 0.82 (95%CI: 0.76-0.88) in middle-

© The Author(s) 2021. Open Access This article is licensed under a Creative Commons Attribution 4.0
International License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted use,
sharing, adaptation, distribution and reproduction in any medium or format, for any purpose, even commercially, as long
as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license,
and indicate if changes were made.

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