Evidence map›Paper›PMID 25456366›Full record

ArticleThe Lancet. Oncology2014

RNA biomarkers associated with metastatic progression in prostate cancer: a multi-institutional high-throughput analysis of SChLAP1.

John R Prensner, Shuang Zhao, Nicholas Erho, Matthew Schipper, Matthew K Iyer, Saravana M Dhanasekaran, Cristina Magi-Galluzzi, Rohit Mehra, Anirban Sahu, Javed Siddiqui and 9 more

Open access · greenAbstract readComparative StudyMulticenter Study
PubMed Full text at PMC Publisher
In one paragraph

Article in The Lancet. Oncology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 147 papers, 3 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
147citing papers in PubMed, 3 pooled it
10.2field-weighted citation impact, top 1% 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

147 citing papers in PubMed, 3 syntheses or guidelines pooled it, 269 citations in OpenAlex.

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  16. lncRNA HOTAIR and Cardiovascular diseases.Functional & integrative genomics · 2024
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87 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

19 authors at 6 institutions in 2 countries.

John R PrensnerMichigan Center for Translational Pathology, University of Michigan Medical School, Ann Arbor, MI, USA.
Shuang ZhaoDepartment of Radiation Oncology, University of Michigan Medical School, Ann Arbor, MI, USA.
Nicholas ErhoGenomeDx Biosciences, Vancouver, BC, Canada.
Matthew SchipperDepartment of Radiation Oncology, University of Michigan Medical School, Ann Arbor, MI, USA.
Matthew K IyerMichigan Center for Translational Pathology, University of Michigan Medical School, Ann Arbor, MI, USA.
Saravana M DhanasekaranMichigan 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.
Cristina Magi-GalluzziAnatomic Pathology, Robert J Tomsich Pathology and Laboratory Medicine Institute, Cleveland Clinic, Cleveland, OH, USA.
Rohit MehraMichigan 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; Comprehensive Cancer Center, University of Michigan Medical School, Ann Arbor, MI, USA.
Anirban SahuMichigan Center for Translational Pathology, University of Michigan Medical School, 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.
Elai DavicioniGenomeDx Biosciences, Vancouver, BC, Canada.
Robert B DenDepartment of Radiation Oncology, Thomas Jefferson University, Philadelphia, PA, USA.
Adam P DickerDepartment of Radiation Oncology, Thomas Jefferson University, Philadelphia, PA, USA.
R Jeffrey KarnesDepartment of Urology, Mayo Clinic, Rochester, MN, USA.
John T WeiDepartment of Urology, University of Michigan Medical School, Ann Arbor, MI, USA.
Eric A KleinGlickman Urological and Kidney Institute, Cleveland Clinic, Cleveland, OH, USA.
Robert B JenkinsDepartment of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, USA.
Arul M ChinnaiyanMichigan 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 Urology, University of Michigan Medical School, Ann Arbor, MI, USA; Comprehensive Cancer Center, University of Michigan Medical School, Ann Arbor, MI, USA; Howard Hughes Medical Institute, University of Michigan Medical School, Ann Arbor, MI, USA.
Felix Y FengMichigan Center for Translational Pathology, University of Michigan Medical School, Ann Arbor, MI, USA; Department of Radiation Oncology, University of Michigan Medical School, Ann Arbor, MI, USA; Comprehensive Cancer Center, University of Michigan Medical School, Ann Arbor, MI, USA. Electronic address: ffeng@med.umich.edu.
University of Michigan–Ann Arbor · USCleveland Clinic · USGenome British Columbia · CAMayo Clinic in Arizona · USThomas Jefferson University · USMichigan Center for Translational Pathology · US

Funding

X-Ray Crystallography and Macromolecular CharacterizationP30CA056036 · NCI · THOMAS JEFFERSON UNIVERSITY · PI DANIEL P SILVER · 1995 to 2026
$94.8M
MICHIGAN MEDICAL SCIENTIST TRAINING PROGRAMT32GM007863 · NIGMS · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI COLLINS, KATHLEEN L. · 1985 to 2024
$38.3M
VACCINIA PSA FOR ANDROGEN-MODULATED POST-SURGICAL RECURRENCE OF PROSTATE CANCERP50CA069568 · NCI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI COONEY, KATHLEEN A · 1995 to 2013
$31.3M
Tissue/InformaticsP50CA186786 · NCI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI Robert Timothy Dess · 2014 to 2026
$27.6M
Epitomic Biomarkers of Prostate CancerU01CA111275 · NCI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI CHINNAIYAN, ARUL M, RUBIN, MARK A. · 2004 to 2015
$6.8M
Molecuar Sub-typing of Prostate Cancer Based on Recurrent Gene FusionsR01CA132874 · NCI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI CHINNAIYAN, ARUL M · 2009 to 2013
$1.2M
Howard Hughes Medical InstituteNCI NIH HHS P30 CA056036NCI NIH HHS P50 CA069568NCI NIH HHS P50 CA186786NCI NIH HHS P50CA69568NCI NIH HHS R01 CA132874NCI NIH HHS R01CA132874-01A1NCI NIH HHS U01 CA111275NCI NIH HHS UO1 CA111275NIGMS NIH HHS T32 GM007863
6 · The paper itself

Abstract

backgroundImproved clinical predictors for disease progression are needed for localised prostate cancer, since only a subset of patients develop recurrent or refractory disease after first-line treatment. Therefore, we undertook an unbiased analysis to identify RNA biomarkers associated with metastatic progression after prostatectomy.

methodsProstate cancer samples from patients treated with radical prostatectomy at three academic institutions were analysed for gene expression by a high-density Affymetrix GeneChip platform, encompassing more than 1 million genomic loci. In a discovery cohort, all protein-coding genes and known long non-coding RNAs were ranked by fold change in expression between tumours that subsequently metastasised versus those that did not. The top ranked gene was then validated for its prognostic value for metastatic progression in three additional independent cohorts. 95% of the gene expression assays were done in a Clinical Laboratory Improvements Amendments certified laboratory facility. All genes were assessed for their ability to predict metastatic progression by receiver-operating-curve area-under-the-curve analyses. Multivariate analyses were done for the primary endpoint of metastatic progression, with variables including Gleason score, preoperative prostate-specific antigen concentration, seminal vesicle invasion, surgical margin status, extracapsular extension, lymph node invasion, and expression of the highest ranked gene.

findings1008 patients were included in the study: 545 in the discovery cohort and 463 in the validation cohorts. The long non-coding RNA SChLAP1 was identified as the highest-ranked overexpressed gene in cancers with metastatic progression. Validation in three independent cohorts confirmed the prognostic value of SChLAP1 for metastatic progression. On multivariate modelling, SChLAP1 expression (high vs low) independently predicted metastasis within 10 years (odds ratio [OR] 2·45, 95% CI 1·70-3·53; p<0·0001). The only other variable that independently predicted metastasis within 10 years was Gleason score (8-10 vs 5-7; OR 2·14, 95% CI 1·77-2·58; p<0·0001).

interpretationWe identified and validated high SChLAP1 expression as significantly prognostic for metastatic disease progression of prostate cancer. Our findings suggest that further development of SChLAP1 as a potential biomarker, for treatment intensification in aggressive prostate cancer, warrants future study.

fundingProstate Cancer Foundation, National Institutes of Health, Department of Defense, Early Detection Research Network, Doris Duke Charitable Foundation, and Howard Hughes Medical Institute.

Indexed as

High-Throughput Nucleotide SequencingAgedBiomarkers, TumorCase-Control StudiesDisease ProgressionFollow-Up StudiesGene Expression ProfilingHumansLymphatic MetastasisMaleMiddle AgedNeoplasm GradingNeoplasm InvasivenessNeoplasm Recurrence, LocalNeoplasm StagingPrognosisBiomarkers, TumorProstate-Specific AntigenRNA, Long Noncoding

Identifiers

PMID25456366
PMCPMC4559342
OpenAlexW2031320118

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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.