Evidence map›Paper›PMID 37438741›Full record

ArticleBMC cancer2023

Next-generation sequencing reveals mitogenome diversity in plasma extracellular vesicles from colorectal cancer patients.

Tonje Bjørnetrø, Paula A Bousquet, Kathrine Røe Redalen, Anne-Marie Siebke Trøseid, Torben Lüders, Espen Stang, Adriana M Sanabria, Christin Johansen, Anniken Jørlo Fuglestad, Christian Kersten and 2 more

Registry-linked trialOpen access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in BMC cancer, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT01816607 (Functional MRI of Hypoxia-mediated Rectal Cancer Aggressiveness), which is not on this map. Cited by 5 papers.

0numbers the graph read from it
0cells of the map it votes in
5citing papers in PubMed
0.9field-weighted citation impact, top 25% 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.

NCT01816607 completednot on this map

Functional MRI of Hypoxia-mediated Rectal Cancer Aggressiveness

TypeobservationalSponsorUniversity Hospital, AkershusRan2013 to 2017Enrolled192ConditionsRectal Diseases, Rectal Neoplasms, Gastrointestinal Diseases, Gastrointestinal NeoplasmsArmsnew functional magnetic resonance imaging (MRI) protocols
3 · Its place in the literature

Who cites it

5 citing papers in PubMed, 6 citations in OpenAlex.

  1. Review
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  5. 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

12 authors at 4 institutions in 1 country.

Tonje BjørnetrøDepartment of Oncology, Akershus University Hospital, P.O. Box 1000, 1478, Lørenskog, Norway. tonje.bjornetro@ahus.no.ORCID http://orcid.org/0000-0003-2110-5875
Paula A BousquetDepartment of Oncology, Akershus University Hospital, P.O. Box 1000, 1478, Lørenskog, Norway.
Kathrine Røe RedalenDepartment of Physics, Norwegian University of Science and Technology, Trondheim, Norway.ORCID http://orcid.org/0000-0002-1172-4632
Anne-Marie Siebke TrøseidDepartment of Biochemistry, Oslo University Hospital Ullevål, Oslo, Norway.
Torben LüdersDepartment of Clinical Molecular Biology, Akershus University Hospital, Lørenskog, Norway.ORCID http://orcid.org/0000-0001-5176-7808
Espen StangDepartment of Pathology, Oslo University Hospital Rikshospitalet, Oslo, Norway.
Adriana M SanabriaDepartment of Oncology, Akershus University Hospital, P.O. Box 1000, 1478, Lørenskog, Norway.ORCID http://orcid.org/0000-0001-7780-7441
Christin JohansenDepartment of Oncology, Akershus University Hospital, P.O. Box 1000, 1478, Lørenskog, Norway.
Anniken Jørlo FuglestadDepartment of Oncology, Akershus University Hospital, P.O. Box 1000, 1478, Lørenskog, Norway.ORCID http://orcid.org/0000-0002-7369-3894
Christian KerstenDepartment of Oncology, Akershus University Hospital, P.O. Box 1000, 1478, Lørenskog, Norway.
Sebastian MeltzerDepartment of Oncology, Akershus University Hospital, P.O. Box 1000, 1478, Lørenskog, Norway.ORCID http://orcid.org/0000-0001-6640-3927
Anne Hansen ReeDepartment of Oncology, Akershus University Hospital, P.O. Box 1000, 1478, Lørenskog, Norway.ORCID http://orcid.org/0000-0002-8264-3223
Akershus University Hospital · NOUniversity of Oslo · NOOslo University Hospital · NONorwegian University of Science and Technology · NO

Funding

Helse Sør-Øst RHF 2018054Helse Sør-Øst RHF 2019109Kreftforeningen 5740692
6 · The paper itself

Abstract

backgroundRecent reports have demonstrated that the entire mitochondrial genome can be secreted in extracellular vesicles (EVs), but the biological attributes of this cell-free mitochondrial DNA (mtDNA) remain insufficiently understood. We used next-generation sequencing to compare plasma EV-derived mtDNA to that of whole blood (WB), peripheral blood mononuclear cells (PBMCs), and formalin-fixed paraffin-embedded (FFPE) tumor tissue from eight rectal cancer patients and WB and fresh-frozen (FF) tumor tissue from eight colon cancer patients.

methodsTotal DNA was isolated before the mtDNA was enriched by PCR with either two primer sets generating two long products or multiple primer sets (for the FFPE tumors), prior to the sequencing. mtDNA diversity was assessed as the total variant number, level of heteroplasmy (mutant mtDNA copies mixed with wild-type copies), variant distribution within the protein-coding genes, and the predicted functional effect of the variants in the different sample types. Differences between groups were compared by paired Student's t-test or ANOVA with Dunnett's multiple comparison tests when comparing matched samples from patients. Mann-Whitney U test was used when comparing differences between the cancer types and patient groups. Pearson correlation analysis was performed.

resultsIn both cancer types, EV mtDNA presented twice as many variants and had significantly more low-level heteroplasmy than WB mtDNA. The EV mtDNA variants were clustered in the coding regions, and the proportion of EV mtDNA variants that were missense mutations (i.e., estimated to moderately affect the mitochondrial protein function) was significantly higher than in WB and tumor tissues. Nonsense mutations (i.e., estimated to highly affect the mitochondrial protein function) were only observed in the tumor tissues and EVs.

conclusionTaken together, plasma EV mtDNA in CRC patients exhibits a high degree of diversity.

trial registrationClinicalTrials.gov: NCT01816607 . Registered 22 March 2013.

Indexed as

Cell-Free Nucleic AcidsColonic NeoplasmsExtracellular VesiclesGenome, MitochondrialDNA, MitochondrialHigh-Throughput Nucleotide SequencingHumansLeukocytes, MononuclearMitochondrial ProteinsCell-Free Nucleic AcidsDNA, MitochondrialMitochondrial ProteinsColorectal cancerExtracellular vesiclesmtDNANext-generation sequencing

Identifiers

PMID37438741
PMCPMC10337118
OpenAlexW4384068014

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Registered trials

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.