Evidence map›Paper›PMID 33812851›Full record

ArticleEuropean urology oncology2022

Development of a Whole-urine, Multiplexed, Next-generation RNA-sequencing Assay for Early Detection of Aggressive Prostate Cancer.

Andi K Cani, Kevin Hu, Chia-Jen Liu, Javed Siddiqui, Yingye Zheng, Sumin Han, Srinivas Nallandhighal, Daniel H Hovelson, Lanbo Xiao, Trinh Pham and 11 more

Open access · greenAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in European urology oncology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.

0numbers the graph read from it
0cells of the map it votes in
10citing papers in PubMed
1.3field-weighted citation impact, top 19% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

10 citing papers in PubMed, 14 citations in OpenAlex.

  1. Review
  2. Article
  3. Review
  4. Review
  5. Review
  6. Review
  7. Biomarkers for Prostate Cancer: From Diagnosis to Treatment.Diagnostics (Basel, Switzerland) · 2023
    Review
  8. The Expression of Proto-OncogeneInternational journal of molecular sciences · 2022
    Review
  9. Article
  10. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

21 authors at 3 institutions in 1 country.

Andi K CaniMichigan Center for Translational Pathology, University of Michigan Medical School, Ann Arbor, MI, USA; Molecular and Cellular Pathology Graduate Program, University of Michigan Medical School, Ann Arbor, MI, USA; Department of Pathology, University of Michigan Medical School, Ann Arbor, MI, USA; Rogel Cancer Center, University of Michigan, Ann Arbor, MI, USA.
Kevin HuMichigan Center for Translational Pathology, University of Michigan Medical School, Ann Arbor, MI, USA; Department of Computational Medicine and Bioinformatics, University of Michigan Medical School, Ann Arbor, MI, USA.
Chia-Jen LiuMichigan Center for Translational Pathology, University of Michigan Medical School, Ann Arbor, MI, USA; Department of Pathology, University of Michigan Medical School, Ann Arbor, MI, USA; Rogel Cancer Center, University of Michigan, Ann Arbor, MI, USA.
Javed SiddiquiMichigan Center for Translational Pathology, University of Michigan Medical School, Ann Arbor, MI, USA; Department of Pathology, University of Michigan Medical School, Ann Arbor, MI, USA.
Yingye ZhengPublic Health Sciences Division, Fred Hutchinson Cancer Center, Seattle, WA, USA.
Sumin HanMichigan Center for Translational Pathology, University of Michigan Medical School, Ann Arbor, MI, USA; Department of Pathology, University of Michigan Medical School, Ann Arbor, MI, USA.
Srinivas NallandhighalDepartment of Urology, University of Michigan Medical School, Ann Arbor, MI, USA.
Daniel H HovelsonMichigan Center for Translational Pathology, University of Michigan Medical School, Ann Arbor, MI, USA; Department of Pathology, University of Michigan Medical School, Ann Arbor, MI, USA; Department of Computational Medicine and Bioinformatics, University of Michigan Medical School, Ann Arbor, MI, USA.
Lanbo XiaoMichigan Center for Translational Pathology, University of Michigan Medical School, Ann Arbor, MI, USA; Department of Pathology, University of Michigan Medical School, Ann Arbor, MI, USA; Rogel Cancer Center, University of Michigan, Ann Arbor, MI, USA.
Trinh PhamDepartment of Urology, University of Michigan Medical School, Ann Arbor, MI, USA.
Nicholas W EyrichDepartment of Urology, University of Michigan Medical School, Ann Arbor, MI, USA.
Heng ZhengMichigan Center for Translational Pathology, University of Michigan Medical School, Ann Arbor, MI, USA; Department of Pathology, University of Michigan Medical School, Ann Arbor, MI, USA; Rogel Cancer Center, University of Michigan, Ann Arbor, MI, USA.
Randy VinceDepartment of Urology, University of Michigan Medical School, Ann Arbor, MI, USA.
Jeffrey J TosoianMichigan Center for Translational Pathology, University of Michigan Medical School, Ann Arbor, MI, USA; Rogel Cancer Center, University of Michigan, Ann Arbor, MI, USA; Department of Urology, University of Michigan Medical School, Ann Arbor, MI, USA.
Ganesh S PalapattuRogel Cancer Center, University of Michigan, Ann Arbor, MI, USA; Department of Urology, University of Michigan Medical School, Ann Arbor, MI, USA.
Todd M MorganRogel Cancer Center, University of Michigan, Ann Arbor, MI, USA; Department of Urology, University of Michigan Medical School, Ann Arbor, MI, USA.
John T WeiMichigan Center for Translational Pathology, University of Michigan Medical School, Ann Arbor, MI, USA; Department of Urology, University of Michigan Medical School, Ann Arbor, MI, USA.
Aaron M UdagerMichigan Center for Translational Pathology, University of Michigan Medical School, Ann Arbor, MI, USA; Department of Pathology, University of Michigan Medical School, Ann Arbor, MI, USA; Rogel Cancer Center, University of Michigan, Ann Arbor, MI, USA.
Arul M ChinnaiyanMichigan Center for Translational Pathology, University of Michigan Medical School, Ann Arbor, MI, USA; Molecular and Cellular Pathology Graduate Program, University of Michigan Medical School, Ann Arbor, MI, USA; Department of Pathology, University of Michigan Medical School, Ann Arbor, MI, USA; Rogel Cancer Center, University of Michigan, Ann Arbor, MI, USA; Department of Urology, University of Michigan Medical School, Ann Arbor, MI, USA.
Scott A TomlinsMichigan Center for Translational Pathology, University of Michigan Medical School, Ann Arbor, MI, USA; Molecular and Cellular Pathology Graduate Program, University of Michigan Medical School, Ann Arbor, MI, USA; Department of Pathology, University of Michigan Medical School, Ann Arbor, MI, USA; Rogel Cancer Center, University of Michigan, Ann Arbor, MI, USA; Department of Urology, University of Michigan Medical School, Ann Arbor, MI, USA. Electronic address: tomlinss@med.umich.edu.
Simpa S SalamiMichigan Center for Translational Pathology, University of Michigan Medical School, Ann Arbor, MI, USA; Rogel Cancer Center, University of Michigan, Ann Arbor, MI, USA; Department of Urology, University of Michigan Medical School, Ann Arbor, MI, USA. Electronic address: simpa@med.umich.edu.
University of Michigan · USFred Hutch Cancer Center · USMichigan Center for Translational Pathology · US

Funding

XenograftP30CA046592 · NCI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI Alexey I Nesvizhskii · 1988 to 2026
$178.2M
Training Program in Translational ResearchT32GM113900 · NIGMS · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI LIEBERMAN, ANDREW P, NIKOLOVSKA-COLESKA, ZANETA · 2016 to 2020
$991k
NCI NIH HHS P30 CA046592NIGMS NIH HHS T32 GM113900
6 · The paper itself

Abstract

backgroundDespite biomarker development advances, early detection of aggressive prostate cancer (PCa) remains challenging. We previously developed a clinical-grade urine test (Michigan Prostate Score [MiPS]) for individualized aggressive PCa risk prediction. MiPS combines serum prostate-specific antigen (PSA), the TMPRSS2:ERG (T2:ERG) gene fusion, and PCA3 lncRNA in whole urine after digital rectal examination (DRE).

objectiveTo improve on MiPS with a novel next-generation sequencing (NGS) multibiomarker urine assay for early detection of aggressive PCa. DESIGN, SETTING, AND

participantsPreclinical development and validation of a post-DRE urine RNA NGS assay (Urine Prostate Seq [UPSeq]) assessing 84 PCa transcriptomic biomarkers, including T2:ERG, PCA3, additional PCa fusions/isoforms, mRNAs, lncRNAs, and expressed mutations. Our UPSeq model was trained on 73 patients and validated on a held-out set of 36 patients representing the spectrum of disease (benign to grade group [GG] 5 PCa). OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The area under the receiver operating characteristic curve (AUC) of UPSeq was compared with PSA, MiPS, and other existing models/biomarkers for predicting GG ≥3 PCa. RESULTS AND LIMITATIONS: UPSeq demonstrated high analytical accuracy and concordance with MiPS, and was able to detect expressed germline HOXB13 and somatic SPOP mutations. In an extreme design cohort (n = 109; benign/GG 1 vs GG ≥3 PCa, stratified to exclude GG 2 cancer in order to capture signal difference between extreme ends of disease), UPSeq showed differential expression for T2:ERG.T1E4 (1.2 vs 78.8 median normalized reads, p < 0.00001) and PCA3 (1024 vs 2521, p = 0.02), additional T2:ERG splice isoforms, and other candidate biomarkers. Using machine learning, we developed a 15-transcript model on the training set (n = 73) that outperformed serum PSA and sequencing-derived MiPS in predicting GG ≥3 PCa in the held-out validation set (n = 36; AUC 0.82 vs 0.69 and 0.69, respectively).

conclusionsThese results support the potential utility of our novel urine-based RNA NGS assay to supplement PSA for improved early detection of aggressive PCa. PATIENT SUMMARY: We have developed a new urine-based test for the detection of aggressive prostate cancer, which promises improvement upon current biomarker tests.

Indexed as

ProstateProstatic NeoplasmsAntigens, NeoplasmBiomarkers, TumorEarly Detection of CancerHigh-Throughput Nucleotide SequencingHumansMaleNuclear ProteinsProstate-Specific AntigenRepressor ProteinsRNAAntigens, NeoplasmBiomarkers, TumorNuclear ProteinsProstate-Specific AntigenRepressor ProteinsRNASPOP protein, humanAlgorithmBiomarkersEarly detectionMachine learningMutationsNext-generation sequencingProstate cancerRNATranscriptomeUrine detection

Identifiers

PMID33812851
PMCPMC11345851
OpenAlexW3145635697

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.