Evidence map›Paper›PMID 32380981›Full record

ArticleBMC cancer2020

Chromosomal instability in untreated primary prostate cancer as an indicator of metastatic potential.

Eric T Miller, Sungyong You, Radu M Cadaneanu, Minhyung Kim, Junhee Yoon, Sandy T Liu, Xinmin Li, Lorna Kwan, Jennelle Hodge, Michael J Quist and 5 more

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

Article in BMC cancer, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.

0numbers the graph read from it
0cells of the map it votes in
15citing papers in PubMed
1.5field-weighted citation impact, top 14% 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

15 citing papers in PubMed, 27 citations in OpenAlex.

  1. Review
  2. Article
  3. Article
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  6. Article
  7. Review
  8. Article
  9. Article
  10. Article
  11. Mechanisms of chromosomal instability (CIN) tolerance in aggressive tumors: surviving the genomic chaos.Chromosome research : an international journal on the molecular, supramolecular and evolutionary aspects of chromosome biology · 2023
    Review
  12. Article
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  14. Article
  15. Article
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

15 authors at 3 institutions in 1 country.

Eric T MillerDepartment of Urology, David Geffen School of Medicine at UCLA, Box 951738, 10833 Le Conte Ave 66-188 CHS UCLA, Los Angeles, CA, 90095, USA.
Sungyong YouDepartment of Biomedical Sciences, Cedars-Sinai Medical Center, California, Los Angeles, USA.
Radu M CadaneanuDepartment of Urology, David Geffen School of Medicine at UCLA, Box 951738, 10833 Le Conte Ave 66-188 CHS UCLA, Los Angeles, CA, 90095, USA.
Minhyung KimDepartment of Surgery, Cedars-Sinai Medical Center, California, Los Angeles, USA.
Junhee YoonDepartment of Surgery, Cedars-Sinai Medical Center, California, Los Angeles, USA.
Sandy T LiuDepartment of Urology, David Geffen School of Medicine at UCLA, Box 951738, 10833 Le Conte Ave 66-188 CHS UCLA, Los Angeles, CA, 90095, USA.
Xinmin LiDepartment of Pathology, David Geffen School of Medicine at UCLA, California, Los Angeles, USA.
Lorna KwanDepartment of Urology, David Geffen School of Medicine at UCLA, Box 951738, 10833 Le Conte Ave 66-188 CHS UCLA, Los Angeles, CA, 90095, USA.
Jennelle HodgeDepartment of Biomedical Sciences, Cedars-Sinai Medical Center, California, Los Angeles, USA.
Michael J QuistDepartment of Medicine, Division of Hematology-Oncology, David Geffen School of Medicine at UCLA, California, Los Angeles, USA.
Catherine S GrassoDepartment of Surgery, Cedars-Sinai Medical Center, California, Los Angeles, USA.
Michael S LewisDepartment of Pathology, Greater Los Angeles Veterans Affairs Health System, California, Los Angeles, USA.
Beatrice S KnudsenDepartment of Biomedical Sciences, Cedars-Sinai Medical Center, California, Los Angeles, USA.
Michael R FreemanDepartment of Biomedical Sciences, Cedars-Sinai Medical Center, California, Los Angeles, USA.
Isla P GarrawayDepartment of Urology, David Geffen School of Medicine at UCLA, Box 951738, 10833 Le Conte Ave 66-188 CHS UCLA, Los Angeles, CA, 90095, USA. igarraway@mednet.ucla.edu.
Cedars-Sinai Medical Center · USUniversity of California, Los Angeles · USVA Greater Los Angeles Healthcare System · US

Funding

Women's CancersP30CA016042 · NCI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI Samuel Wheeler French · 1985 to 2026
$134.5M
UCLA SPORE IN PROSTATE CANCERP50CA092131 · NCI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI FREEMAN, MICHAEL R · 2002 to 2023
$42.6M
Prostate Cancer Bone Metastasis: Biology and TargetingP01CA098912 · NCI · EMORY UNIVERSITY · PI ZAYZAFOON, MAJD · 2003 to 2019
$24.0M
Supporting African American Churches to Promote Cancer ScreeningU54CA143931 · NCI · CHARLES R. DREW UNIVERSITY OF MED & SCI · PI VADGAMA, JAYDUTT V. · 2009 to 2022
$19.7M
Training and Mentoring ProgramsU54CA143930 · NCI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI PIETRAS, RICHARD JOSEPH · 2009 to 2020
$7.5M
In vivo effects of sulforaphane supplementation on normal human prostateR01CA131255 · NCI · FRED HUTCHINSON CANCER RESEARCH CENTER · PI KNUDSEN, BEATRICE S, LIN, DANIEL W. · 2009 to 2013
$1.8M
Jean Perkins Foundation NAMovember Foundation GAP6 Unique TMAsNCI NIH HHS P01 CA098912NCI NIH HHS P01 CA098912-09NCI NIH HHS P30 CA016042NCI NIH HHS P50 CA092131NCI NIH HHS P50CA092131NCI NIH HHS R01 CA131255NCI NIH HHS R01CA131255NCI NIH HHS U54 CA143930NCI NIH HHS U54 CA143931Prostate Cancer Foundation 17CHAL04Prostate Cancer Foundation Creativity AwardStephen Spielberg Foundation NAU.S. Department of Defense PC130244U.S. Department of Defense PC131996
6 · The paper itself

Abstract

backgroundMetastatic prostate cancer (PC) is highly lethal. The ability to identify primary tumors capable of dissemination is an unmet need in the quest to understand lethal biology and improve patient outcomes. Previous studies have linked chromosomal instability (CIN), which generates aneuploidy following chromosomal missegregation during mitosis, to PC progression. Evidence of CIN includes broad copy number alterations (CNAs) spanning > 300 base pairs of DNA, which may also be measured via RNA expression signatures associated with CNA frequency. Signatures of CIN in metastatic PC, however, have not been interrogated or well defined. We examined a published 70-gene CIN signature (CIN70) in untreated and castration-resistant prostate cancer (CRPC) cohorts from The Cancer Genome Atlas (TCGA) and previously published reports. We also performed transcriptome and CNA analysis in a unique cohort of untreated primary tumors collected from diagnostic prostate needle biopsies (PNBX) of localized (M0) and metastatic (M1) cases to determine if CIN was linked to clinical stage and outcome.

methodsPNBX were collected from 99 patients treated in the VA Greater Los Angeles (GLA-VA) Healthcare System between 2000 and 2016. Total RNA was extracted from high-grade cancer areas in PNBX cores, followed by RNA sequencing and/or copy number analysis using OncoScan. Multivariate logistic regression analyses permitted calculation of odds ratios for CIN status (high versus low) in an expanded GLA-VA PNBX cohort (n = 121).

resultsThe CIN70 signature was significantly enriched in primary tumors and CRPC metastases from M1 PC cases. An intersection of gene signatures comprised of differentially expressed genes (DEGs) generated through comparison of M1 versus M0 PNBX and primary CRPC tumors versus metastases revealed a 157-gene "metastasis" signature that was further distilled to 7-genes (PC-CIN) regulating centrosomes, chromosomal segregation, and mitotic spindle assembly. High PC-CIN scores correlated with CRPC, PC-death and all-cause mortality in the expanded GLA-VA PNBX cohort. Interestingly, approximately 1/3 of M1 PNBX cases exhibited low CIN, illuminating differential pathways of lethal PC progression.

conclusionsMeasuring CIN in PNBX by transcriptome profiling is feasible, and the PC-CIN signature may identify patients with a high risk of lethal progression at the time of diagnosis.

Indexed as

AneuploidyGene Expression Regulation, NeoplasticAgedAged, 80 and overBiomarkers, TumorBiopsy, NeedleChromosomal InstabilityDatabases, GeneticDisease ProgressionGene Expression ProfilingHumansMaleMiddle AgedNeoplasm MetastasisNeoplasm StagingPrognosisBiomarkers, TumorChromosomal instabilityCINMetastasesProstate cancerProstate needle biopsiesTCGA

Identifiers

PMID32380981
PMCPMC7204307
OpenAlexW3023359653

What OpenQuestion holds

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LicenceCC BY
Read underepoch 390

Registered trials

None linked

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.