The Future of

Prostate Cancer
Biomarkers Is Multiplexed
Combining urinary biomarkers improves clinical utility
and provides a more robust evaluation

Why are multiplex urinary biomarkers necessary?

Individual urinary biomarkers evaluate a single anomaly in prostate cancer cells.
However, prostate cancers are multifocal with heterogeneous molecular composition.
Combining urinary biomarkers allows a complete evaluation of prostate cancer cells
while minimizing the risk of missing a foci of cancer or a unique mutation that drives
clinical outcomes.

Developing multiplex urine biomarkers for prostate cancer

Individual biomarkers are identified via multiple techniques, such as microarray analysis
or RNA-Seq for mRNA and quantitative mass spectroscopy of proteins. Biomarkers are
then confirmed via qPCR, immunoassay, and other technologies using urine samples from The future
men with or without prostate cancer.1 The multiplexed biomarker panel is then analyzed There are several tests that combine different classes of biomarkers under development,
by logistic regression analysis and compared to preexisting biomarkers. including tests that examine gene expression.

Commercially available multiplex urine biomarkers UPSeq

Recently, Urine Prostate Seq (UPSeq) was developed using multiplex NGS RNA
Test Method Targets Sensitivity Specifcity
sequencing and machine learning to filter 84 target transcripts (fusion genes, mRNAs,
germline variants, etc.) into a 15-biomarker panel. In a recent study, UPSeq outperformed
SelectMDx2 RT-qPCR DLX1, 91% 36%
HOXC6, the combination of PCA3 and TMPRS22-ERG in predicting high-risk prostate cancer.6
serum PSA
ExoGrail
Michigan Prostate Score Transcription- PCA3, 73% 93.2% ExoGrail, another multiplex test being developed, combines engrailed-2 (EN2), a
(MiPS)3 mediated TMPRSS2- transcription factor important for early mammalian development, and an 11-gene probe of
amplification ERG,
cell-free mRNA.7 It holds promise for further risk stratifying patients prior to prostate biopsy.
assay serum PSA
REFERENCES
ExoDx Prostate Intelliscore4 Exosomal RNA ERG, 92% 34% 1. Eskra, Jillian N., et al. “Approaches to urinary detection of prostate cancer.” Prostate Cancer and Prostatic Diseases 22.3 (2019): 362–81.
2. Van Neste, Leander, et al. “Detection of high-grade prostate cancer using a urinary molecular biomarker–based risk score.”
PCA3, European Urology 70.5 (2016): 740–48.
SPDEF 3. Leyten, Gisele H. J. M., et al. “Prospective multicentre evaluation of PCA3 and TMPRSS2-ERG gene fusions as diagnostic and prognostic
urinary biomarkers for prostate cancer.” European Urology. 65.3 (2014): 534–42.
4. McKiernan, James, et al. “A novel urine exosome gene expression assay to predict high-grade prostate cancer at initial biopsy.”
Prostarix5 Quantitative Sarcosine, 25–90% 24–90% JAMA Oncology 2.7 (2016): 882.
LC-MS/MS alanine, 5. McDunn, Jonathan, et al. “Metabolomics and its application to the development of clinical laboratory tests for prostate cancer.”
Journal of International Federation of Clinical Chemistry and Laboratory Medicine 25.2 (2015): 92-104.
glycine, 6. Cani, Andi K., et al. “Development of a whole-urine, multiplexed, next-generation RNA-sequencing assay for early detection of aggressive
glutamate prostate cancer.” European Urology Oncology (2021).
7. Connell, Shea, et al. “Integration of urinary EN2 protein & cell-free RNA data in the development of a multivariable risk model
for the detection of prostate cancer prior to biopsy.” Cancers 13.9 (2021): 2102.