Detection of circulating KRAS mutant DNA in extracellular vesicles using droplet digital PCR in patients with colon cancer

Extracellular vesicles secreted by tumor cells contain double-stranded DNA called extracellular vesicle DNA (evDNA). EvDNA is genomic DNA that reflects cancer driver mutations. However, the significance of evDNA analysis in the diagnosis and surveillance of colon cancer remains unclear. This study a...

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Published inFrontiers in oncology Vol. 12; p. 1067210
Main Authors Choi, Jeesoo, Cho, Ho Yeon, Jeon, Jeongseok, Kim, Kyung-A, Han, Yoon Dae, Ahn, Joong Bae, Wortzel, Inbal, Lyden, David, Kim, Han Sang
Format Journal Article
LanguageEnglish
Published Switzerland Frontiers Media S.A 15.12.2022
Subjects
cancer
colon cancer
ddPCR
exosome
extracellular vesicle
liquid biopsy
Oncology
ddPCR
colon cancer
exosomal DNA
cell-free DNA
cancer
exosome
extracellular vesicle
liquid biopsy
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Summary:Extracellular vesicles secreted by tumor cells contain double-stranded DNA called extracellular vesicle DNA (evDNA). EvDNA is genomic DNA that reflects cancer driver mutations. However, the significance of evDNA analysis in the diagnosis and surveillance of colon cancer remains unclear. This study aimed to investigate the clinical utility of extracellular vesicles and evDNA isolated from the plasma of colon cancer patients harboring G12D and G13D mutations. Cell-free DNA (cfDNA) and evDNA were collected from the plasma of 30 patients with colon cancer. mutation status (G12D and G13D) was detected using a droplet digital polymerase chain reaction assay (ddPCR). Sensitivity and specificity were evaluated in patients with wild-type tumors. Mutation status was correlated with carcinoembryonic antigen (CEA) levels and overall survival (OS). Thirty cfDNA and evDNA pairs showed a fractional abundance (FA) ranging from 0 to 45.26% and 0 to 83.81%, respectively. When compared with eight wild-type samples, cfDNA exhibited 70% sensitivity and 100% specificity, whereas evDNA achieved 76.67% sensitivity and 100% specificity. The concentration of evDNA was significantly lower than that of cfDNA, but it obtained a higher FA than cfDNA, while showing a positive correlation with CEA. Our findings demonstrate the feasibility of evDNA as a complementary tool to aid current methods of patient evaluation in the diagnosis and surveillance of colon cancer.
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Edited by: Francesca Negri, University Hospital of Parma, Italy
Reviewed by: Francesco Pepe, University of Naples Federico II, Italy; Reza Shahbazi, Indiana University School of medicine, United States
This article was submitted to Gastrointestinal Cancers: Colorectal Cancer, a section of the journal Frontiers in Oncology
These authors have contributed equally to this work
ISSN:2234-943X
2234-943X
DOI:10.3389/fonc.2022.1067210