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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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Autores principales: Bu, Jiyoon, Lee, Tae Hee, Jeong, Woo-jin, Poellmann, Michael J., Mudd, Kara, Eun, Hyuk Soo, Liu, Elizabeth W., Hong, Seungpyo, Hyun, Sung Hee
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7710035/
https://www.ncbi.nlm.nih.gov/pubmed/33264292
http://dx.doi.org/10.1371/journal.pone.0242145
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author Bu, Jiyoon
Lee, Tae Hee
Jeong, Woo-jin
Poellmann, Michael J.
Mudd, Kara
Eun, Hyuk Soo
Liu, Elizabeth W.
Hong, Seungpyo
Hyun, Sung Hee
author_facet Bu, Jiyoon
Lee, Tae Hee
Jeong, Woo-jin
Poellmann, Michael J.
Mudd, Kara
Eun, Hyuk Soo
Liu, Elizabeth W.
Hong, Seungpyo
Hyun, Sung Hee
author_sort Bu, Jiyoon
collection PubMed
description 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 <0.001) for detecting patients with HER2-positive tumors. The new system also revealed high prognostic capability of cfDNA, as the concentration of cfDNA was highly associated with the survival outcomes. Our novel technology demonstrates the potential to achieve efficient detection of cfDNA that may serve as a reliable biomarker for gastric tumor.
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spelling pubmed-77100352020-12-03 Enhanced detection of cell-free DNA (cfDNA) enables its use as a reliable biomarker for diagnosis and prognosis of gastric cancer Bu, Jiyoon Lee, Tae Hee Jeong, Woo-jin Poellmann, Michael J. Mudd, Kara Eun, Hyuk Soo Liu, Elizabeth W. Hong, Seungpyo Hyun, Sung Hee PLoS One Research Article 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 <0.001) for detecting patients with HER2-positive tumors. The new system also revealed high prognostic capability of cfDNA, as the concentration of cfDNA was highly associated with the survival outcomes. Our novel technology demonstrates the potential to achieve efficient detection of cfDNA that may serve as a reliable biomarker for gastric tumor. Public Library of Science 2020-12-02 /pmc/articles/PMC7710035/ /pubmed/33264292 http://dx.doi.org/10.1371/journal.pone.0242145 Text en © 2020 Bu et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Bu, Jiyoon
Lee, Tae Hee
Jeong, Woo-jin
Poellmann, Michael J.
Mudd, Kara
Eun, Hyuk Soo
Liu, Elizabeth W.
Hong, Seungpyo
Hyun, Sung Hee
Enhanced detection of cell-free DNA (cfDNA) enables its use as a reliable biomarker for diagnosis and prognosis of gastric cancer
title Enhanced detection of cell-free DNA (cfDNA) enables its use as a reliable biomarker for diagnosis and prognosis of gastric cancer
title_full Enhanced detection of cell-free DNA (cfDNA) enables its use as a reliable biomarker for diagnosis and prognosis of gastric cancer
title_fullStr Enhanced detection of cell-free DNA (cfDNA) enables its use as a reliable biomarker for diagnosis and prognosis of gastric cancer
title_full_unstemmed Enhanced detection of cell-free DNA (cfDNA) enables its use as a reliable biomarker for diagnosis and prognosis of gastric cancer
title_short Enhanced detection of cell-free DNA (cfDNA) enables its use as a reliable biomarker for diagnosis and prognosis of gastric cancer
title_sort enhanced detection of cell-free dna (cfdna) enables its use as a reliable biomarker for diagnosis and prognosis of gastric cancer
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7710035/
https://www.ncbi.nlm.nih.gov/pubmed/33264292
http://dx.doi.org/10.1371/journal.pone.0242145
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