Evidence map›Paper›PMID 27903987›Full record

ArticleOncotarget2017

Mapping heterogeneity in patient-derived melanoma cultures by single-cell RNA-seq.

Tobias Gerber, Edith Willscher, Henry Loeffler-Wirth, Lydia Hopp, Dirk Schadendorf, Manfred Schartl, Ulf Anderegg, Gray Camp, Barbara Treutlein, Hans Binder and 1 more

Open access · diamondAbstract read
In one paragraph

Article in Oncotarget, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 52 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
52citing papers in PubMed, 1 pooled it
4.9field-weighted citation impact, top 4% 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

52 citing papers in PubMed, 1 synthesis or guideline pooled it, 78 citations in OpenAlex.

  1. Pooled it
  2. Trial
  3. Mutation-informed gene pairs to predict melanoma metastasis.Cell communication and signaling : CCS · 2026
    Article
  4. Article
  5. Article
  6. Article
  7. Article
  8. Review
  9. Review
  10. Review
  11. Review
  12. Article
  13. Article
  14. Review
  15. Article
  16. Article
  17. Article
  18. Article
  19. Article
  20. Cancer cell metabolic plasticity in migration and metastasis.Clinical & experimental metastasis · 2021
    Review
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

11 authors at 4 institutions in 2 countries.

Tobias GerberDepartment of Evolutionary Genetics, Max Planck Institute for Evolutionary Anthropology Leipzig, 04103 Leipzig, Germany.
Edith WillscherInterdisciplinary Center for Bioinformatics, University of Leipzig, 04107 Leipzig, Germany.
Henry Loeffler-WirthInterdisciplinary Center for Bioinformatics, University of Leipzig, 04107 Leipzig, Germany.
Lydia HoppInterdisciplinary Center for Bioinformatics, University of Leipzig, 04107 Leipzig, Germany.
Dirk SchadendorfDepartment of Dermatology, Venereology and Allergology, University Hospital Essen, 45147 Essen, Germany.
Manfred SchartlDepartment of Physiological Chemistry, University of Würzburg, Biozentrum, Am Hubland, 97074 Würzburg, Germany.
Ulf AndereggDepartment of Dermatology, Venereology and Allergology, University of Leipzig, 04103 Leipzig, Germany.
Gray CampDepartment of Evolutionary Genetics, Max Planck Institute for Evolutionary Anthropology Leipzig, 04103 Leipzig, Germany.
Barbara TreutleinDepartment of Evolutionary Genetics, Max Planck Institute for Evolutionary Anthropology Leipzig, 04103 Leipzig, Germany.
Hans BinderInterdisciplinary Center for Bioinformatics, University of Leipzig, 04107 Leipzig, Germany.
Manfred KunzDepartment of Dermatology, Venereology and Allergology, University of Leipzig, 04103 Leipzig, Germany.
Leipzig University · DEMax Planck Institute for Evolutionary Anthropology · DEEssen University Hospital · DEUniversity of Würzburg · DE

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Recent technological advances in single-cell genomics make it possible to analyze cellular heterogeneity of tumor samples. Here, we applied single-cell RNA-seq to measure the transcriptomes of 307 single cells cultured from three biopsies of three different patients with a BRAF/NRAS wild type, BRAF mutant/NRAS wild type and BRAF wild type/NRAS mutant melanoma metastasis, respectively. Analysis based on self-organizing maps identified sub-populations defined by multiple gene expression modules involved in proliferation, oxidative phosphorylation, pigmentation and cellular stroma. Gene expression modules had prognostic relevance when compared with gene expression data from published melanoma samples and patient survival data. We surveyed kinome expression patterns across sub-populations of the BRAF/NRAS wild type sample and found that CDK4 and CDK2 were consistently highly expressed in the majority of cells, suggesting that these kinases might be involved in melanoma progression. Treatment of cells with the CDK4 inhibitor palbociclib restricted cell proliferation to a similar, and in some cases greater, extent than MAPK inhibitors. Finally, we identified a low abundant sub-population in this sample that highly expressed a module containing ABC transporter ABCB5, surface markers CD271 and CD133, and multiple aldehyde dehydrogenases (ALDHs). Patient-derived cultures of the BRAF mutant/NRAS wild type and BRAF wild type/NRAS mutant metastases showed more homogeneous single-cell gene expression patterns with gene expression modules for proliferation and ABC transporters. Taken together, our results describe an intertumor and intratumor heterogeneity in melanoma short-term cultures which might be relevant for patient survival, and suggest promising targets for new treatment approaches in melanoma therapy.

Indexed as

Biomarkers, TumorChromosome MappingGenetic HeterogeneityGenetic Predisposition to DiseaseSequence Analysis, RNASingle-Cell AnalysisAdultAgedCell Line, TumorCell ProliferationComputational BiologyCyclin-Dependent Kinase 4Epigenesis, GeneticFemaleGene Expression ProfilingGene Expression Regulation, NeoplasticBiomarkers, TumorCyclin-Dependent Kinase 4palbociclibPiperazinesProto-Oncogene Proteins B-rafPyridinesmelanomasingle cell transcriptome sequencingstem cells

Identifiers

PMID27903987
PMCPMC5352202
OpenAlexW2554682097

What OpenQuestion holds

Textmetadata
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.