Evidence map›Paper›PMID 33276026›Full record

ArticleJournal of hepatology2021

Integrative molecular characterisation of gallbladder cancer reveals micro-environment-associated subtypes.

Chirag Nepal, Bin Zhu, Colm J O'Rourke, Deepak Kumar Bhatt, Donghyuk Lee, Lei Song, Difei Wang, Alison L Van Dyke, Hyoyoung Choo-Wosoba, Zhiwei Liu and 18 more

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

Article in Journal of hepatology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 55 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
55citing papers in PubMed, 1 pooled it
5.9field-weighted citation impact, top 3% 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

55 citing papers in PubMed, 1 synthesis or guideline pooled it, 77 citations in OpenAlex.

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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

28 authors at 9 institutions in 5 countries.

Chirag NepalBiotech Research and Innovation Centre, Department of Health and Medical Sciences, University of Copenhagen, Denmark.
Bin ZhuDivision of Cancer Epidemiology and Genetics, NIH, Rockville, MD, USA.
Colm J O'RourkeBiotech Research and Innovation Centre, Department of Health and Medical Sciences, University of Copenhagen, Denmark.
Deepak Kumar BhattBiotech Research and Innovation Centre, Department of Health and Medical Sciences, University of Copenhagen, Denmark.
Donghyuk LeeDivision of Cancer Epidemiology and Genetics, NIH, Rockville, MD, USA.
Lei SongDivision of Cancer Epidemiology and Genetics, NIH, Rockville, MD, USA.
Difei WangDivision of Cancer Epidemiology and Genetics, NIH, Rockville, MD, USA.
Alison L Van DykeDivision of Cancer Epidemiology and Genetics, NIH, Rockville, MD, USA.
Hyoyoung Choo-WosobaDivision of Cancer Epidemiology and Genetics, NIH, Rockville, MD, USA.
Zhiwei LiuDivision of Cancer Epidemiology and Genetics, NIH, Rockville, MD, USA.
Allan HildesheimDivision of Cancer Epidemiology and Genetics, NIH, Rockville, MD, USA.
Alisa M GoldsteinDivision of Cancer Epidemiology and Genetics, NIH, Rockville, MD, USA.
Michael DeanDivision of Cancer Epidemiology and Genetics, NIH, Rockville, MD, USA.
Juan LaFuente-BarqueroBiotech Research and Innovation Centre, Department of Health and Medical Sciences, University of Copenhagen, Denmark.
Scott LawrenceCancer Genomics Research Laboratory, Leidos Biomedical Research, Frederick National Laboratory for Cancer Research, Frederick, MD, USA.
Karun MutrejaCancer Genomics Research Laboratory, Leidos Biomedical Research, Frederick National Laboratory for Cancer Research, Frederick, MD, USA.
Mary E OlanichCancer Genomics Research Laboratory, Leidos Biomedical Research, Frederick National Laboratory for Cancer Research, Frederick, MD, USA.
Justo Lorenzo BermejoStatistical Genetics Research Group, Institute of Medical Biometry and Informatics, University of Heidelberg, Heidelberg, Germany.
CGR Exome Studies GroupDivision of Cancer Epidemiology and Genetics, NIH, Rockville, MD, USA; The CGR Exome Studies Group, NIH, Rockville, MD, USA.
Catterina FerreccioDepartment of Public Health, School of Medicine, Pontificia Universidad Católica de Chile, Santiago, Chile; Advanced Center for Chronic Diseases (ACCDiS), FONDAP, Santiago, Chile.
Juan Carlos RoaDepartment of Pathology, School of Medicine, Pontificia Universidad Católica de Chile, Santiago, Chile.
Asif RashidDepartment of Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Ann W HsingStanford Cancer Institute and Stanford Prevention Research Center, Department of Medicine, Stanford School of Medicine, Stanford, CA, USA.
Yu-Tang GaoDepartment of Epidemiology, Shanghai Cancer Institute, Shanghai, China.
Stephen J ChanockDivision of Cancer Epidemiology and Genetics, NIH, Rockville, MD, USA.
Juan Carlos ArayaAdvanced Center for Chronic Diseases (ACCDiS), FONDAP, Santiago, Chile; Hospital Dr. Hernán Henríquez Aravena, Temuco, Chile; Department of Pathology, Faculty of Medicine, Universidad de La Frontera, Temuco, Chile.
Jesper B AndersenBiotech Research and Innovation Centre, Department of Health and Medical Sciences, University of Copenhagen, Denmark. Electronic address: jesper.andersen@bric.ku.dk.
Jill KoshiolDivision of Cancer Epidemiology and Genetics, NIH, Rockville, MD, USA. Electronic address: koshiolj@mail.nih.gov.
National Cancer Institute · USUniversity of Copenhagen · DKLeidos (United States) · USPontificia Universidad Católica de Chile · CLHeidelberg University · DEShanghai Cancer Institute · CNStanford Cancer InstituteThe University of Texas MD Anderson Cancer Center · USUniversidad de La Frontera · CL

Funding

Etiology of Biliary Tract CancerZIACP010218 · NCI · DIVISION OF CANCER EPIDEMIOLOGY AND GENETICS · PI KOSHIOL, JILL · 2011 to 2025
$30.4M
Intramural NIH HHS ZIA CP010218
6 · The paper itself

Abstract

BACKGROUND &

aimsGallbladder cancer (GBC) is the most common type of biliary tract cancer, but the molecular mechanisms involved in gallbladder carcinogenesis remain poorly understood. In this study, we applied integrative genomics approaches to characterise GBC and explore molecular subtypes associated with patient survival.

methodsWe profiled the mutational landscape of GBC tumours (whole-exome sequencing on 92, targeted sequencing on 98, in total 190 patients). In a subset (n = 45), we interrogated the matched transcriptomes, DNA methylomes, and somatic copy number alterations. We explored molecular subtypes identified through clustering tumours by genes whose expression was associated with survival in 47 tumours and validated subtypes on 34 publicly available GBC cases.

resultsExome analysis revealed TP53 was the most mutated gene. The overall mutation rate was low (median 0.82 Mut/Mb). APOBEC-mediated mutational signatures were more common in tumours with higher mutational burden. Aflatoxin-related signatures tended to be highly clonal (present in ≥50% of cancer cells). Transcriptome-wide survival association analysis revealed a 95-gene signature that stratified all GBC patients into 3 subtypes that suggested an association with overall survival post-resection. The 2 poor-survival subtypes were associated with adverse clinicopathologic features (advanced stage, pN1, pM1), immunosuppressive micro-environments (myeloid-derived suppressor cell accumulation, extensive desmoplasia, hypoxia) and T cell dysfunction, whereas the good-survival subtype showed the opposite features.

conclusionThese data suggest that the tumour micro-environment and immune profiles could play an important role in gallbladder carcinogenesis and should be evaluated in future clinical studies, along with mutational profiles. LAY SUMMARY: Gallbladder cancer is highly fatal, and its causes are poorly understood. We evaluated gallbladder tumours to see if there were differences between tumours in genetic information such as DNA and RNA. We found evidence of aflatoxin exposure in these tumours, and immune cells surrounding the tumours were associated with survival.

Indexed as

CarcinogenesisGallbladder NeoplasmsTranscriptomeAflatoxinsCarcinogensDNA Copy Number VariationsExome SequencingFemaleGene Expression ProfilingHumansMaleMiddle AgedMutationNeoplasm StagingSurvival AnalysisTumor MicroenvironmentAflatoxinsCarcinogensTP53 protein, humanTumor Suppressor Protein p53AflatoxinGallbladder cancerImmunogenomicsMicro-environmentMolecular subgroups

Identifiers

PMID33276026
PMCPMC8058239
OpenAlexW3108066728

What OpenQuestion holds

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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.