Evidence map›Paper›PMID 25986914›Full record

ArticleProstate cancer and prostatic diseases2015

High-throughput transcriptomic analysis nominates proteasomal genes as age-specific biomarkers and therapeutic targets in prostate cancer.

S G Zhao, W C Jackson, V Kothari, M J Schipper, N Erho, J R Evans, C Speers, D A Hamstra, Y S Niknafs, P L Nguyen and 7 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Prostate cancer and prostatic diseases, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.

0numbers the graph read from it
0cells of the map it votes in
6citing papers in PubMed
–field-weighted citation impact
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

6 citing papers in PubMed.

  1. Article
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  6. 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

17 authors.

S G ZhaoDepartment of Radiation Oncology, University of Michigan Medical School, Ann Arbor, MI, USA.
W C JacksonDepartment of Radiation Oncology, University of Michigan Medical School, Ann Arbor, MI, USA.
V KothariDepartment of Radiation Oncology, University of Michigan Medical School, Ann Arbor, MI, USA.
M J Schipper1] Department of Radiation Oncology, University of Michigan Medical School, Ann Arbor, MI, USA [2] Department of Biostatistics, University of Michigan Medical School, Ann Arbor, MI, USA.
N ErhoGenomeDx Biosciences Inc., Vancouver, British Columbia, Canada.
J R EvansDepartment of Radiation Oncology, University of Michigan Medical School, Ann Arbor, MI, USA.
C SpeersDepartment of Radiation Oncology, University of Michigan Medical School, Ann Arbor, MI, USA.
D A Hamstra1] Department of Radiation Oncology, University of Michigan Medical School, Ann Arbor, MI, USA [2] Comprehensive Cancer Center, University of Michigan Medical School, Ann Arbor, MI, USA.
Y S NiknafsMichigan Center for Translational Pathology, University of Michigan Medical School, Ann Arbor, MI, USA.
P L NguyenDepartment of Radiation Oncology, Harvard University, Boston, MA, USA.
E M SchaefferDepartments of Urology, Oncology, and Pathology, Johns Hopkins University, Baltimore, MD, USA.
A E RossDepartments of Urology, Oncology, and Pathology, Johns Hopkins University, Baltimore, MD, USA.
R B DenDepartment of Radiation Oncology, Thomas Jefferson University, Philadelphia, PA, USA.
E A KleinGlickman Urological and Kidney Institute, Cleveland Clinic, Cleveland, OH, USA.
R B JenkinsDepartment of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MI, USA.
E DavicioniGenomeDx Biosciences Inc., Vancouver, British Columbia, Canada.
F Y Feng1] Department of Radiation Oncology, University of Michigan Medical School, Ann Arbor, MI, USA [2] Comprehensive Cancer Center, University of Michigan Medical School, Ann Arbor, MI, USA [3] Michigan Center for Translational Pathology, University of Michigan Medical School, Ann Arbor, MI, USA.

Funding

Translational Research Central ServicesP30CA006973 · NCI · JOHNS HOPKINS UNIVERSITY · PI Rosalie Wollett · 1985 to 2026
$208.6M
Women's Cancer ProgramP30CA015083 · NCI · MAYO CLINIC ROCHESTER · PI Felicity Enders · 1985 to 2026
$151.3M
MICHIGAN MEDICAL SCIENTIST TRAINING PROGRAMT32GM007863 · NIGMS · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI COLLINS, KATHLEEN L. · 1985 to 2024
$38.3M
CELLULAR AND MOLECULAR BIOLOGY AT MICHIGANT32GM007315 · NIGMS · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI PUTHENVEEDU, MANOJKUMAR A · 1985 to 2021
$12.8M
NCI NIH HHS P30 CA006973NCI NIH HHS P30 CA015083NIGMS NIH HHS T32 GM007315NIGMS NIH HHS T32 GM007863
6 · The paper itself

Abstract

backgroundAlthough prostate cancer (PCa) is hypothesized to differ in nature between younger versus older patients, the underlying molecular distinctions are poorly understood. We hypothesized that high-throughput transcriptomic analysis would elucidate biological differences in PCas arising in younger versus older men, and would nominate potential age-specific biomarkers and therapeutic targets.

methodsThe high-density Affymetrix GeneChip platform, encompassing >1 million genomic loci, was utilized to assess gene expression in 1090 radical prostatectomy samples from patients with long-term follow-up. We identified genes associated with metastatic progression by 10 years post-treatment in younger (age<65) versus older (age⩾65) patients, and ranked these genes by their prognostic value. We performed Gene Set Enrichment Analysis (GSEA) to nominate biological concepts that demonstrated age-specific effects, and validated a target by treating with a clinically available drug in three PCa cell lines derived from younger men.

resultsOver 80% of the top 1000 prognostic genes in younger and older men were specific to that age group. GSEA nominated the proteasome pathway as the most differentially prognostic in younger versus older patients. High expression of proteasomal genes conferred worse prognosis in younger but not older men on univariate and multivariate analysis. Bortezomib, a Food and Drug Administration approved proteasome inhibitor, decreased proliferation in three PCa cell lines derived from younger patients.

conclusionsOur data show significant global differences in prognostic genes between older versus younger men. We nominate proteasomeal gene expression as an age-specific biomarker and potential therapeutic target specifically in younger men. Limitations of our study include clinical differences between cohorts, and increased comorbidities and lower survival in older patients. These intriguing findings suggest that current models of PCa biology do not adequately represent genetic heterogeneity of PCa related to age, and future clinical trials would benefit from stratification based on age.

Indexed as

Biomarkers, TumorTranscriptomeAgedAge FactorsAntineoplastic AgentsCell Line, TumorCell ProliferationFollow-Up StudiesGene Expression ProfilingHumansMaleMiddle AgedMolecular Targeted TherapyNeoplasm GradingNeoplasm MetastasisNeoplasm StagingAntineoplastic AgentsBiomarkers, TumorProteasome Endopeptidase ComplexProteasome Inhibitors

Identifiers

PMID25986914
PMCPMC4579590

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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.