Evidence map›Paper›PMID 36323735›Full record

ArticleScientific reports2022

Detection of mitochondrial DNA mutations in circulating mitochondria-originated extracellular vesicles for potential diagnostic applications in pancreatic adenocarcinoma.

Kunwar Somesh Vikramdeo, Shashi Anand, Mohammad Aslam Khan, Moh'd Khushman, Martin J Heslin, Seema Singh, Ajay Pratap Singh, Santanu Dasgupta

Open access · goldAbstract read
In one paragraph

Article in Scientific reports, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.

0numbers the graph read from it
0cells of the map it votes in
24citing papers in PubMed
3.0field-weighted citation impact, top 7% 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

24 citing papers in PubMed, 36 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 2 institutions in 1 country.

Kunwar Somesh VikramdeoCancer Biology Program, Department of Pathology, Mitchell Cancer Institute, College of Medicine, University of South Alabama, 1660 Springhill Avenue, Mobile, AL, 36604, USA.
Shashi AnandCancer Biology Program, Department of Pathology, Mitchell Cancer Institute, College of Medicine, University of South Alabama, 1660 Springhill Avenue, Mobile, AL, 36604, USA.
Mohammad Aslam KhanCancer Biology Program, Department of Pathology, Mitchell Cancer Institute, College of Medicine, University of South Alabama, 1660 Springhill Avenue, Mobile, AL, 36604, USA.
Moh'd KhushmanDepartment of Medical Oncology, Mitchell Cancer Institute, University of South Alabama, Mobile, AL, 36604, USA.
Martin J HeslinCancer Biology Program, Department of Pathology, Mitchell Cancer Institute, College of Medicine, University of South Alabama, 1660 Springhill Avenue, Mobile, AL, 36604, USA.
Seema SinghCancer Biology Program, Department of Pathology, Mitchell Cancer Institute, College of Medicine, University of South Alabama, 1660 Springhill Avenue, Mobile, AL, 36604, USA.
Ajay Pratap SinghCancer Biology Program, Department of Pathology, Mitchell Cancer Institute, College of Medicine, University of South Alabama, 1660 Springhill Avenue, Mobile, AL, 36604, USA. asingh@southalabama.edu.
Santanu DasguptaCancer Biology Program, Department of Pathology, Mitchell Cancer Institute, College of Medicine, University of South Alabama, 1660 Springhill Avenue, Mobile, AL, 36604, USA. dasgupta@southalabama.edu.
University of South Alabama · USUSA Mitchell Cancer Institute · US

Funding

A novel molecular cross-talk driving pancreatic cancer progressionR01CA224306 · NCI · UNIVERSITY OF SOUTH ALABAMA · PI SINGH, AJAY PRATAP · 2018 to 2022
$1.7M
NCI NIH HHS R01 CA224306
6 · The paper itself

Abstract

There is a complete lack of highly sensitive and specific biomarkers for early pancreatic ductal adenocarcinoma (PDAC) diagnosis, limiting multi-modal therapeutic options. Mitochondrial DNA (mtDNA) is an excellent resource for biomarker discovery because of its high copy number and increased mutational frequency in cancer cells. We examined if mtDNA mutations can be detected in circulating extracellular vesicles (EVs) of PDAC patients and used for discerning between cancer and non-cancer subjects. A greater yield of circulating EVs (~ 1.4 fold; p = 0.002) was obtained in PDAC patients (n = 20) than non-cancer (NC) individuals (n = 10). PDAC-EVs contained a higher quantity of total DNA (~ 5.5 folds; p = 0.0001) than NC-EVs and had greater enrichment of mtDNA (~ 14.02-fold; p = 0.0001). PDAC-EVs also had higher levels of cardiolipin (a mitochondrial inner-membrane phospholipid), suggestive of their mitochondrial origin. All mtDNA mutations in PDAC-EVs were unique and frequency was remarkably higher. Most mtDNA mutations (41.5%) in PDAC-EVs were in the respiratory complex-I (RCI) (ND1-ND6), followed by the RCIII gene (CYTB; 11.2%). Among the non-coding genes, D-Loop and RNR2 exhibited the most mutations (15.2% each). Altogether, our study establishes, for the first time, that mtDNA mutations can be detected in circulating EVs and potentially serve as a tool for reliable PDAC diagnosis.

Indexed as

AdenocarcinomaCarcinoma, Pancreatic DuctalExtracellular VesiclesPancreatic NeoplasmsDNA, MitochondrialHumansMitochondriaMutationDNA, Mitochondrial

Identifiers

PMID36323735
PMCPMC9630429
OpenAlexW4308147073

What OpenQuestion holds

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LicenceCC BY
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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.