Evidence map›Paper›PMID 34595842›Full record

ArticleJournal of extracellular vesicles2021

Extracellular vesicles are the primary source of blood-borne tumour-derived mutant KRAS DNA early in pancreatic cancer.

Daniel W Hagey, Maximilian Kordes, André Görgens, Metoboroghene O Mowoe, Joel Z Nordin, Carlos Fernández Moro, J-Matthias Löhr, Samir El Andaloussi

Open access · goldAbstract read
In one paragraph

Article in Journal of extracellular vesicles, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.

0numbers the graph read from it
0cells of the map it votes in
32citing papers in PubMed
2.8field-weighted citation impact, top 8% 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

32 citing papers in PubMed, 46 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

8 authors at 3 institutions in 4 countries.

Daniel W HageyDepartment of Laboratory Medicine, Karolinska Institutet, Stockholm, Sweden.ORCID 0000-0001-9246-6235
Maximilian KordesDepartment of Clinical Science, Intervention and Technology, Karolinska Institutet, Stockholm, Sweden.
André GörgensDepartment of Laboratory Medicine, Karolinska Institutet, Stockholm, Sweden.
Metoboroghene O MowoeDepartment of Laboratory Medicine, Karolinska Institutet, Stockholm, Sweden.
Joel Z NordinDepartment of Laboratory Medicine, Karolinska Institutet, Stockholm, Sweden.
Carlos Fernández MoroDepartment of Laboratory Medicine, Karolinska Institutet, Stockholm, Sweden.
J-Matthias LöhrDepartment of Clinical Science, Intervention and Technology, Karolinska Institutet, Stockholm, Sweden.
Samir El AndaloussiDepartment of Laboratory Medicine, Karolinska Institutet, Stockholm, Sweden.
Karolinska Institutet · SEKarolinska University Hospital · SEUniversity of Cape Town · ZA

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Up to now, the field of liquid biopsies has focused on circulating tumour DNA and cells, though extracellular vesicles (EVs) have been of increasing interest in recent years. Thus, reported sources of tumour-derived nucleic acids include leukocytes, platelets and apoptotic bodies (AB), as well as large (LEV) and small (SEV) EVs. Despite these competing claims, there has yet to be a standardized comparison of the tumour-derived DNA associated with different components of blood. To address this issue, we collected twenty-three blood samples from seventeen patients with pancreatic cancers of known mutant KRAS G12 genotype, and divided them into two groups based on the time of patient survival following sampling. After collecting red and white blood cells, we subjected 1 ml aliquots of platelet rich plasma to differential centrifugation in order to separate the platelets, ABs, LEVs, SEVs and soluble proteins (SP) present. We then confirmed the enrichment of specific blood components in each differential centrifugation fraction using electron microscopy, Western blotting, nanoparticle tracking analysis and bead-based multiplex flow cytometry assays. By targeting wild type and tumour-specific mutant KRAS alleles using digital PCR, we found that the levels of mutant KRAS DNA were highest in association with LEVs and SEVs early, and with SEVs and SP late in disease progression. Importantly, we established that SEVs were the most enriched in tumour-derived DNA throughout disease progression, and verified this association using size exclusion chromatography. This work provides important direction for the rapidly expanding field of liquid biopsies by supporting an increased focus on EVs as a source of tumour-derived DNA.

Indexed as

Circulating Tumor DNADNAExtracellular VesiclesHumansLiquid BiopsyPancreatic NeoplasmsProto-Oncogene Proteins p21(ras)Circulating Tumor DNADNAProto-Oncogene Proteins p21(ras)apoptotic bodiescancer diagnosticsctDNAdigital PCRexosomesextracellular vesiclesliquid biopsymicrovesiclespancreatic cancerplatelets

Identifiers

PMID34595842
PMCPMC8485184
OpenAlexW3203499399

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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.