Cell-Free DNA Concentration Associated with Injury Severity and Survival in ICU Animal Study using CIRCULOGENE’s Proprietary Liquid Biopsy Technology
cfDNA levels correlate significantly with biomarkers of multiorgan damage in first abstract stemming from DOD research grant to The Geneva Foundation
BIRMINGHAM, Ala. – CIRCULOGENE molecular diagnostics laboratory today announced the first results stemming from a federal research grant investigating the use of liquid biopsy markers to assess battlefield trauma. CIRCULOGENE is a subcontractor to The Geneva Foundation (Geneva), which was awarded a $1.5 million U.S. Department of Defense (DOD) grant in 2019 to develop liquid biopsy diagnostics for the rapid and accurate assessment and management of traumatic brain injury (TBI) and other battlefield trauma.
The objective of the current study was to determine if circulating cell-free DNA (cfDNA) correlates with early mortality and expression of benchmark biomarkers in animals with smoke inhalation injury (SII) and cutaneous burns. The promising results, which demonstrate that circulating cfDNA is a robust diagnostic tool for major organ injury severity quantification after trauma, were presented recently at the Circulating Biomarkers World Congress 2020 in Coronado Island, California. The abstract presented was titled “Early Post Injury Systemic Cell-free DNA is Associated with Survival in 72-hour Intensive Care Unit Study in Swine with Smoke Inhalation and Burns.”
“TBI, alone and in combination with major organ injury, causes the vast majority of combat-related deaths,” explained research project Principal Investigator Andriy Batchinsky, M.D., a Geneva employee. “Identifying specific and accurate injury severity markers and diagnostic tools are critical for the development of effective therapeutic interventions,” said Dr. Batchinsky.
“We know that traumatic injury and burns damage cells, which release fragments of damaged DNA, which then enter systemic circulation,” said study lead author Jae H. Choi, MSc, Ph.D., DVSc, Co-Principal Investigator of the Geneva Foundation. “With the increasing clinical sensitivity and specificity of liquid biopsy and its high throughput and quick turnaround, there is now a new wave of interest in this approach.”
Researchers reported a strong correlation of circulating cfDNA with damage associated molecular patterns (DAMPs) that indicate organ damage. Among these biomarkers of organ damage were: high mobility group box 1 protein (HMGB1); toll-like receptor 4 (TLR4); neutrophil gelatinase-associated lipocalin (NGAL) for acute kidney injury (AKI); and glial fibrillary acidic protein (GFAP) for brain damage.
“The data show a very significant correlation,” said CIRCULOGENE Chief Scientific Officer and study co-author Chen-Hsiung Yeh, Ph.D. “We’re excited that our laboratory’s extraction-free, loss-free, micro-liquid biopsy platform shows promise in helping establish cfDNA as a sensitive biomarker of injury severity, and eventually to track and map injured tissue-of-origin from cfDNA. We look forward to additional research stemming from this grant to help address the needs of battlefield patients by applying precision medicine concepts to trauma care.”
Study authors found that: cfDNA concentrations were significantly higher in non-surviving animals vs. survivors; circulating cfDNA levels positively correlated with NGAL, HMGB1, total plasma protein concentration (TPPC), GFAP and TLR4 levels for all timepoints; and that cfDNA was significantly associated with mortality at 72 hours. Researchers concluded:
- Higher cfDNA concentration was seen in animals with early mortality
- cfDNA significantly correlated with DAMPs, including kidney and brain damage biomarkers, indicating that cfDNA concentration is a useful biomarker from injury
- cfDNA could be a useful candidate for point-of-care testing and guidance for therapeutic interventions
Unlike standard DNA quantification methods, which are unreliable, biased and suffer from significant DNA loss during extraction, CIRCULOGENE’s linear-in-situ amplification (LISA) technology combines loss-free sample preparation with linear cfDNA quantification, resulting in unprecedented accuracy.
The Geneva Foundation Grant is made possible through the Defense Medical Research and Development Program (DMRDP) Precision Trauma Care Research Award (PTCRA), which supports research applying precision medicine concepts to trauma care.
CIRCULOGENE provides biomarker testing for a broad range of cancers, allowing physicians to match results to specific drugs and clinical trials in just one week. Using a single tube of blood (4 mL), CIRCULOGENE can test for circulating genetic mutations and tumor biomarkers among DNA mutations and RNA fusions, including qPCR testing covering 20 NTRK fusions, PD-L1 expression and MSI markers.
CIRCULOGENE is a Clinical Laboratory Improvement Amendments (CLIA) and College of American Pathologists (CAP) certified laboratory and a Verified Vendor of the https://uscontractorregistration.com for the federal System for Award Management. For more information, visit our website, connect with us on LinkedIn, Facebook and Twitter, or email us at firstname.lastname@example.org or call 855-614-7083. Clinicians interested in ordering tests may visit the Contact page on CIRCULOGENE’s website.
This work is supported by the Office of the Assistant Secretary of Defense for Health Affairs, through the Defense Medical Research and Development Program (DMRDP) under Grant No. W81XWH-19-20008 via subcontract S-11001-01 and administered through The Geneva Foundation, Tacoma, WA, PI: Dr. Andriy Batchinsky, M.D.
Opinions, interpretations, conclusions and recommendations are those of the author and are not necessarily endorsed by the Department of Defense. The experiments reported herein were conducted according to the principles set forth in the National Institute of Health Publication No.80-23, Guide for the Care and Use of Laboratory Animals and the Animal Welfare Act of 1966, as amended. In the conduct of research utilizing recombinant DNA, the investigator adhered to NIH Guidelines for research involving recombinant DNA molecules. In the conduct of research involving hazardous organisms or toxins, the investigator adhered to the CDC-NIH Guide for Biosafety in Microbiological and Biomedical Laboratories.”
Headquartered in Birmingham, Ala., CIRCULOGENE is an innovative molecular diagnostics company founded and operated by a team of experienced industry executives and skilled molecular diagnostics scientists. Applying its proprietary laboratory developed test for cfDNA, cfRNA and MSI liquid biopsies, CIRCULOGENE has developed a next-generation sequencing (NGS) method to provide full genomic load analysis from one standard tube of blood in one week, enabling more accurate data to help clinicians and their patients choose targeted therapies, monitor efficacy and monitor for recurrence. One tube, one week, complete results. Somatic + Germline; Blood + Tissue + Buccal; DNA + RNA + MSI + PD-L1. For more information, visit www.circulogene.com or call 855-614-7083.
About The Geneva Foundation
The Geneva Foundation is a 501(c)3 non-profit organization that advances military medicine through innovative scientific research, exceptional program management, and a dedication to U.S. service members and veterans, their families, and the global community. Geneva is proud to have over 25 years of experience in delivering full spectrum scientific, technical, and program management expertise in the areas of federal grants, federal contracts, industry sponsored clinical trials, and educational services. www.genevaUSA.org
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