Enhanced detection of cell-free DNA (cfDNA) enables its use as a reliable biomarker for diagnosis and prognosis of gastric cancer

Although circulating cell-free DNA (cfDNA) is a promising biomarker for the diagnosis and prognosis of various tumors, clinical correlation of cfDNA with gastric cancer has not been fully understood. To address this, we developed a highly sensitive cfDNA capture system by integrating polydopamine (P...

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Bibliographic Details
Published in:PloS one 2020-12, Vol.15 (12), p.e0242145-e0242145
Main Authors: Bu, Jiyoon, Lee, Tae Hee, Jeong, Woo-Jin, Poellmann, Michael J, Mudd, Kara, Eun, Hyuk Soo, Liu, Elizabeth W, Hong, Seungpyo, Hyun, Sung Hee
Format: Article
Language:English
Subjects:
Adsorption
Adult
Aged
Aged, 80 and over
Antigens
Biological markers
Biology and Life Sciences
Biomarkers
Biomarkers, Tumor - blood
Biomarkers, Tumor - genetics
Biopsy
Blood plasma
Cancer
Cancer research
Cell culture
Cell-Free Nucleic Acids - genetics
Cell-Free Nucleic Acids - isolation & purification
Correlation
Deoxyribonucleic acid
Diagnosis
Diagnostic systems
DNA
DNA identification
Dopamine
Early Detection of Cancer
Engineering
ErbB-2 protein
Female
Gastric cancer
Gene expression
Genetic aspects
Genomic analysis
Humans
Hybrids
Male
Medical diagnosis
Medical prognosis
Medicine and Health Sciences
Metastases
Methods
Middle Aged
Molecular diagnostic techniques
Molecular interactions
Pharmaceutical sciences
Pharmacy
Physical Sciences
Prognosis
Silica
Silicon dioxide
Silicon Dioxide - chemistry
Stomach cancer
Stomach Neoplasms - blood
Stomach Neoplasms - diagnosis
Stomach Neoplasms - genetics
Stomach Neoplasms - pathology
Tumors
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Summary:Although circulating cell-free DNA (cfDNA) is a promising biomarker for the diagnosis and prognosis of various tumors, clinical correlation of cfDNA with gastric cancer has not been fully understood. To address this, we developed a highly sensitive cfDNA capture system by integrating polydopamine (PDA) and silica. PDA-silica hybrids incorporated different molecular interactions to a single system, enhancing cfDNA capture by 1.34-fold compared to the conventional silica-based approach (p = 0.001), which was confirmed using cell culture supernatants. A clinical study using human plasma samples revealed that the diagnostic accuracy of the new system to be superior than the commercially available cfDNA kit, as well as other serum antigen tests. Among the cancer patients, plasma cfDNA levels exhibited a good correlation with the size of a tumor. cfDNA was also predicative of distant metastasis, as the median cfDNA levels of metastatic cancer patients were ~60-fold higher than those without metastasis (p = 0.008). Furthermore, high concordance between tissue biopsy and cfDNA genomic analysis was found, as HER2 expression in cfDNA demonstrated an area under ROC curve (AUC) of 0.976 (p
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0242145