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Research Article
Heather Wilson-Robles
Texas A&M University
Corresponding Author
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Background: Nucleosomes consist of DNA wrapped around a histone octamer core like thread on a spool to condense DNA as chromatin into chromosomes. Diseases such as cancer or inflammation lead to cell death, chromatin fragmentation and release of nucleosomes into the blood. The Nu.QTM platform measures circulating nucleosomes in the blood of humans that result from disease and has been used to detect and identify cancer even at early stages. The objectives of this study are to quantify and better characterize nucleosomes in dogs with various stages of hemangiosarcoma (HSA) using this ELISA-based assay.
Samples from 77 dogs with a confirmed diagnosis of hemangiosarcoma and 134 healthy controls were utilized for this study. The HSA samples were recruited from the Texas A&M University Small Animal Clinic (TAMU-SAC) or purchased from biobanks. All control samples were recruited from the TAMU-SAC.
Results: Dogs with hemangiosarcoma had a 6.6-fold increase in their median plasma nucleosome concentrations compared to controls (AUC 92.9%). Elevated nucleosome concentrations were seen at all stages of disease and nucleosome concentrations increased with the stage of the disease.
Conclusion: Plasma nucleosome concentrations are a reliable way to differentiate dogs with hemangiosarcoma from healthy dogs. Further testing is underway to better characterize cancer associated HSA circulating nucleosomes and optimize future diagnostics for canine HSA detection.
Keywords
hemangiosarcoma, dog, canine, nucleosome, H3.1, cell free DNA, plasma, H3
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Competing interest reported. JT, TK, MB and TB are employees of Volition Diagnostics UK Ltd & Volition America, which have patents covering Nu.Q technology and are developers of Nu.QTM assays. Volition Veterinary is a joint venture between Belgian Volition and Texas A&M University. HWR is a paid consultant of Volition Veterinary. TM and JJ have no conflicts of interest to declare. Additional salary support for TM was provided by the Fred and Vola Palmer Chair in Comparative Oncology held by HWR. The Palmers did not play a role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript and only provided financial support for the authors’ salaries (T.M.). This does not alter our adherence to BMC policies on sharing data and materials.
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This preprint is under consideration at BMC Veterinary Research. A preprint is a preliminary version of a manuscript that has not completed peer review at a journal. Research Square does not conduct peer review prior to posting preprints. The posting of a preprint on this server should not be interpreted as an endorsement of its validity or suitability for dissemination as established information or for guiding clinical practice.
Learn more about In Review
Research Article
Heather Wilson-Robles
Texas A&M University
Corresponding Author
Badges
Prescreen
This manuscript passed our Prescreen assessment
Complete author information
Appropriate declaration statements
Potential risks to human health
Prescreen
Peer Review Timeline
CURRENT STATUS: Under Review
Version 1
Posted 18 Mar, 2021
No community comments so far
Review #1 received
Received 31 Mar, 2021
Reviewer #23 agreed
On 12 Mar, 2021
Reviewer #20 agreed
On 12 Mar, 2021
Reviewer #9 agreed
On 12 Mar, 2021
Reviewer #22 agreed
On 12 Mar, 2021
Reviewer #18 agreed
On 12 Mar, 2021
Reviewer #17 agreed
On 12 Mar, 2021
Reviewer #5 agreed
On 12 Mar, 2021
Reviewer #4 agreed
On 12 Mar, 2021
Reviewer #3 agreed
On 12 Mar, 2021
Reviewer #19 agreed
On 12 Mar, 2021
Reviewer #21 agreed
On 12 Mar, 2021
Reviewer #14 agreed
On 12 Mar, 2021
Reviewer #2 agreed
On 12 Mar, 2021
Reviewer #1 agreed
On 12 Mar, 2021
Reviewer #10 agreed
On 12 Mar, 2021
Reviewers invited
Invitations sent on 12 Mar, 2021
Editor assigned
On 12 Mar, 2021
Editor invited
On 12 Mar, 2021
Submission checks complete
On 12 Mar, 2021
First submitted
On 08 Mar, 2021
Metrics
Comments: 0
PDF Downloads: ...
HTML Views: ...
Subject Areas
Veterinary Epidemiology
License:
This work is licensed under a CC BY 4.0 License. Read Full License
Background: Nucleosomes consist of DNA wrapped around a histone octamer core like thread on a spool to condense DNA as chromatin into chromosomes. Diseases such as cancer or inflammation lead to cell death, chromatin fragmentation and release of nucleosomes into the blood. The Nu.QTM platform measures circulating nucleosomes in the blood of humans that result from disease and has been used to detect and identify cancer even at early stages. The objectives of this study are to quantify and better characterize nucleosomes in dogs with various stages of hemangiosarcoma (HSA) using this ELISA-based assay.
Samples from 77 dogs with a confirmed diagnosis of hemangiosarcoma and 134 healthy controls were utilized for this study. The HSA samples were recruited from the Texas A&M University Small Animal Clinic (TAMU-SAC) or purchased from biobanks. All control samples were recruited from the TAMU-SAC.
Results: Dogs with hemangiosarcoma had a 6.6-fold increase in their median plasma nucleosome concentrations compared to controls (AUC 92.9%). Elevated nucleosome concentrations were seen at all stages of disease and nucleosome concentrations increased with the stage of the disease.
Conclusion: Plasma nucleosome concentrations are a reliable way to differentiate dogs with hemangiosarcoma from healthy dogs. Further testing is underway to better characterize cancer associated HSA circulating nucleosomes and optimize future diagnostics for canine HSA detection.
Figure 1
Figure 2
Figure 3
Figure 4
Figure 5
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