Evidence map›Paper›PMID 27612592›Full record

SynthesisEBioMedicine2016

Meta-Analysis of the Luminal and Basal Subtypes of Bladder Cancer and the Identification of Signature Immunohistochemical Markers for Clinical Use.

Vipulkumar Dadhania, Miao Zhang, Li Zhang, Jolanta Bondaruk, Tadeusz Majewski, Arlene Siefker-Radtke, Charles C Guo, Colin Dinney, David E Cogdell, Shizhen Zhang and 6 more

Open access · goldAbstract readMeta-Analysis
In one paragraph

Synthesis in EBioMedicine, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 204 papers, 3 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
204citing papers in PubMed, 3 pooled it
30.8field-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

204 citing papers in PubMed, 3 syntheses or guidelines pooled it, 337 citations in OpenAlex.

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144 more citing papers are in PubMed but not listed here.

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

16 authors at 1 institution in 1 country.

Vipulkumar DadhaniaDepartment of Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX, United States.
Miao ZhangDepartment of Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX, United States.
Li ZhangDepartment of Bioinformatics and Computational Biology, The University of Texas MD Anderson Cancer Center, Houston, TX, United States.
Jolanta BondarukDepartment of Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX, United States.
Tadeusz MajewskiDepartment of Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX, United States.
Arlene Siefker-RadtkeDepartment of Genitourinary Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, United States.
Charles C GuoDepartment of Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX, United States.
Colin DinneyDepartment of Urology, The University of Texas MD Anderson Cancer Center, Houston, TX, United States.
David E CogdellDepartment of Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX, United States.
Shizhen ZhangDepartment of Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX, United States.
Sangkyou LeeDepartment of Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX, United States.
June G LeeDepartment of Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX, United States.
John N WeinsteinDepartment of Bioinformatics and Computational Biology, The University of Texas MD Anderson Cancer Center, Houston, TX, United States.
Keith BaggerlyDepartment of Bioinformatics and Computational Biology, The University of Texas MD Anderson Cancer Center, Houston, TX, United States.
David McConkeyDepartment of Urology, The University of Texas MD Anderson Cancer Center, Houston, TX, United States.
Bogdan CzerniakDepartment of Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX, United States. Electronic address: bczernia@mdanderson.org.
The University of Texas MD Anderson Cancer Center · US

Funding

Tumor Evolution and Metastasis ProgramP30CA016672 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI Fabien Delerue · 1985 to 2026
$290.8M
Targeting Ral GTPases in Bladder CancerP50CA091846 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI DINNEY, COLIN P.N., MCCONKEY, DAVID J. · 2001 to 2018
$37.4M
Batch effects in molecular profiling data on cancers: detection, quantitation, interpretation, and correctionU24CA210949 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI AKBANI, REHAN, MILLS, GORDON B. · 2016 to 2020
$1.9M
Multidisciplinary Subspecialty Pathology Research Fellowship ProgramT32CA163185 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI CZERNIAK, BOGDAN A, KEYOMARSI, KHANDAN · 2011 to 2015
$1.7M
Aurora Kinase A as a Biomarker for the Detection of Bladder CancerR01CA151489 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI CZERNIAK, BOGDAN A · 2010 to 2013
$1.6M
NCI NIH HHS P30 CA016672NCI NIH HHS P50 CA091846NCI NIH HHS R01 CA151489NCI NIH HHS T32 CA163185NCI NIH HHS U24 CA210949
6 · The paper itself

Abstract

backgroundIt has been suggested that bladder cancer can be divided into two molecular subtypes referred to as luminal and basal with distinct clinical behaviors and sensitivities to chemotherapy. We aimed to validate these subtypes in several clinical cohorts and identify signature immunohistochemical markers that would permit simple and cost-effective classification of the disease in primary care centers.

methodsWe analyzed genomic expression profiles of bladder cancer in three cohorts of fresh frozen tumor samples: MD Anderson (n=132), Lund (n=308), and The Cancer Genome Atlas (TCGA) (n=408) to validate the expression signatures of luminal and basal subtypes and relate them to clinical follow-up data. We also used an MD Anderson cohort of archival bladder tumor samples (n=89) and a parallel tissue microarray to identify immunohistochemical markers that permitted the molecular classification of bladder cancer.

findingsBladder cancers could be assigned to two candidate intrinsic molecular subtypes referred to here as luminal and basal in all of the datasets analyzed. Luminal tumors were characterized by the expression signature similar to the intermediate/superficial layers of normal urothelium. They showed the upregulation of PPARγ target genes and the enrichment for FGFR3, ELF3, CDKN1A, and TSC1 mutations. In addition, luminal tumors were characterized by the overexpression of E-Cadherin, HER2/3, Rab-25, and Src. Basal tumors showed the expression signature similar to the basal layer of normal urothelium. They showed the upregulation of p63 target genes, the enrichment for TP53 and RB1 mutations, and overexpression of CD49, Cyclin B1, and EGFR. Survival analyses showed that the muscle-invasive basal bladder cancers were more aggressive when compared to luminal cancers. The immunohistochemical expressions of only two markers, luminal (GATA3) and basal (KRT5/6), were sufficient to identify the molecular subtypes of bladder cancer with over 90% accuracy.

interpretationThe molecular subtypes of bladder cancer have distinct clinical behaviors and sensitivities to chemotherapy, and a simple two-marker immunohistochemical classifier can be used for prognostic and therapeutic stratification.

fundingU.S. National Cancer Institute and National Institute of Health.

Indexed as

Biomarkers, TumorAgedAged, 80 and overCluster AnalysisCohort StudiesFemaleGene Expression ProfilingHumansImmunohistochemistryMaleMiddle AgedMutationNeoplasm InvasivenessNeoplasms, Basal CellNeoplasm StagingPrognosisBiomarkers, TumorBiomarkerBladder cancer

Identifiers

PMID27612592
PMCPMC5078592
OpenAlexW2509266256

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
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.