Evidence map›Paper›PMID 34615513›Full record

ArticleBMC cancer2021

Co-expression of YAP and TAZ associates with chromosomal instability in human cholangiocarcinoma.

Marcell Tóth, Lilija Wehling, Lena Thiess, Fabian Rose, Jennifer Schmitt, Sofia M E Weiler, Carsten Sticht, Carolina De La Torre, Melina Rausch, Thomas Albrecht and 11 more

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

Article in BMC cancer, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.

0numbers the graph read from it
0cells of the map it votes in
14citing papers in PubMed
6.2field-weighted citation impact, top 2% 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

14 citing papers in PubMed, 61 citations in OpenAlex.

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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 4 institutions in 2 countries.

Marcell TóthInstitute of Pathology, University Hospital Heidelberg, Im Neuenheimer Feld 224, 69120, Heidelberg, Germany.
Lilija WehlingInstitute of Pathology, University Hospital Heidelberg, Im Neuenheimer Feld 224, 69120, Heidelberg, Germany.
Lena ThiessInstitute of Pathology, University Hospital Heidelberg, Im Neuenheimer Feld 224, 69120, Heidelberg, Germany.
Fabian RoseInstitute of Pathology, University Hospital Heidelberg, Im Neuenheimer Feld 224, 69120, Heidelberg, Germany.
Jennifer SchmittInstitute of Pathology, University Hospital Heidelberg, Im Neuenheimer Feld 224, 69120, Heidelberg, Germany.
Sofia M E WeilerInstitute of Pathology, University Hospital Heidelberg, Im Neuenheimer Feld 224, 69120, Heidelberg, Germany.
Carsten StichtNGS Core Facility, Medical Faculty Mannheim, Heidelberg University, Heidelberg, Germany.
Carolina De La TorreNGS Core Facility, Medical Faculty Mannheim, Heidelberg University, Heidelberg, Germany.
Melina RauschInstitute of Pathology, University Hospital Heidelberg, Im Neuenheimer Feld 224, 69120, Heidelberg, Germany.
Thomas AlbrechtInstitute of Pathology, University Hospital Heidelberg, Im Neuenheimer Feld 224, 69120, Heidelberg, Germany.
Niels GrabeHamamatsu Tissue Imaging and Analysis Center (TIGA), BioQuant, Heidelberg University, Heidelberg, Germany.
Lea DuweBiotech Research and Innovation Centre (BRIC), Department of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
Jesper B AndersenBiotech Research and Innovation Centre (BRIC), Department of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
Bruno C KöhlerDepartment of Medical Oncology, National Center for Tumor Diseases, University Hospital Heidelberg, Heidelberg, Germany;, Liver Cancer Center Heidelberg, University Hospital Heidelberg, Heidelberg, Germany.
Christoph SpringfeldDepartment of Medical Oncology, National Center for Tumor Diseases, University Hospital Heidelberg, Heidelberg, Germany;, Liver Cancer Center Heidelberg, University Hospital Heidelberg, Heidelberg, Germany.
Arianeb MehrabiDepartment of General Visceral and Transplantation Surgery, University Hospital Heidelberg, Heidelberg, Germany.
Yakup KuluDepartment of General Visceral and Transplantation Surgery, University Hospital Heidelberg, Heidelberg, Germany.
Peter SchirmacherInstitute of Pathology, University Hospital Heidelberg, Im Neuenheimer Feld 224, 69120, Heidelberg, Germany.
Stephanie Roessler *Institute of Pathology, University Hospital Heidelberg, Im Neuenheimer Feld 224, 69120, Heidelberg, Germany.
Benjamin Goeppert *Institute of Pathology, University Hospital Heidelberg, Im Neuenheimer Feld 224, 69120, Heidelberg, Germany.
Kai Breuhahn *Institute of Pathology, University Hospital Heidelberg, Im Neuenheimer Feld 224, 69120, Heidelberg, Germany. kai.breuhahn@med.uni-heidelberg.de.
University Hospital Heidelberg · DEHeidelberg University · DEUniversity of Copenhagen · DKNational Center for Tumor Diseases · DE

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundActivation of the oncogene yes-associated protein (YAP) is frequently detected in intrahepatic cholangiocarcinoma (iCCA); however, the expression pattern and the functional impact of its paralogue WW domain-containing transcription regulator 1 (WWTR1; synonym: TAZ) are not well described in different CCA subtypes.

methodsImmunohistochemical analysis of YAP and TAZ in iCCA and extrahepatic CCA (eCCA) cohorts was performed. YAP/TAZ shuttling and their functional impact on CCA cell lines were investigated. Target genes expression after combined YAP/TAZ inhibition was analyzed.

resultsImmunohistochemical analysis of iCCA and eCCA revealed YAP or TAZ positivity in up to 49.2%; however, oncogene co-expression was less frequent (up to 23%). In contrast, both proteins were jointly detectable in most CCA cell lines and showed nuclear/cytoplasmic shuttling in a cell density-dependent manner. Next to the pro-proliferative function of YAP/TAZ, both transcriptional co-activators cooperated in the regulation of a gene signature that indicated the presence of chromosomal instability (CIN). A correlation between YAP and the CIN marker phospho-H2A histone family member X (pH2AX) was particularly observed in tissues from iCCA and distal CCA (dCCA). The presence of the CIN genes in about 25% of iCCA was statistically associated with worse prognosis.

conclusionsYAP and TAZ activation is not uncoupled from cell density in CCA cells and both factors cooperatively contribute to proliferation and expression of CIN-associated genes. The corresponding group of CCA patients is characterized by CIN and may benefit from YAP/TAZ-directed therapies.

Indexed as

Adaptor Proteins, Signal TransducingBile Duct NeoplasmsBile Ducts, ExtrahepaticBile Ducts, IntrahepaticCell CountCell Line, TumorCholangiocarcinomaChromosomal InstabilityHistonesHumansImmunohistochemistryIntracellular Signaling Peptides and ProteinsPrognosisTissue Array AnalysisTranscriptional Coactivator with PDZ-Binding Motif ProteinsTranscription FactorsAdaptor Proteins, Signal TransducingH2AX protein, humanHistonesIntracellular Signaling Peptides and ProteinsTranscriptional Coactivator with PDZ-Binding Motif ProteinsTranscription FactorsWWTR1 protein, humanYAP1 protein, humanYAP-Signaling ProteinsCell densityCIN25Genomic instabilityHippo pathwayLiver cancer

Identifiers

PMID34615513
PMCPMC8496054
OpenAlexW3203945529

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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.