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A high-sensitivity cfDNA capture enables to detect the BRAF V600E mutation in papillary thyroid carcinoma

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Abstract

Although many efforts have been made to investigate a promising biomarker for the diagnosis of papillary thyroid cancer (PTC), the currently available biomarkers lack the sensitivity to accurately characterize PTC. Here, we established a high-sensitivityt cell-free DNA (cfDNA) detection system using polydopamine-silica (PDA/SiO2) hybrids to enable clinically reliable analysis of PTC. The PDA/SiO2-coated beads improved the detection of DNA by 1.76-fold (p=0.031) compared to the conventional silica-based cfDNA capture system. The PDA-SiO2-coated beads were then applied for the detection of cfDNA from serum samples obtained from 37 PTC patients, and the BRAFV600E mutation status in captured DNA was analyzed using both quantitative polymerase chain reaction (qPCR) and digital droplet PCR (ddPCR). The BRAFV600E mutation status analyzed using both assays demonstrated a strong correlation with the multifocality of PTC, exhibiting area under receiver operating characteristic curve (AUC-ROC) of >0.964 (p<0.001). In contrast, none of the serum antigens or antibodies related to PTC or thyroid functions exhibited clinically significant prediction for detecting PTC patients with multifocal tumors. These findings suggest that cfDNA capture using PDA/SiO2-coated beads is a promising approach for analyzing the BRAF mutation, which can serve as an excellent diagnostic biomarker for PTC.

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Acknowledgement

This work was supported by Basic Science Research Program Funded by Ministry of Science and Technology (Republic of Korea) under grant # NRF-2022R1F1A1075414. It has been also partially supported by NRF under grant # NRF-2020R1A2C4001856/#NRF-2019M3E5D1A02068557, KHIDI under grant #HR20C0025040021, Chungnam National University Hospital Research Fund 2019, the Leaders in Industry-university Cooperation 3.0 Project, and the National Research Foundation of Korea Grant funded by the Korean Government(MOE).

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  1. These authors contributed equally.

Authors and Affiliations

  1. Department of Biomedical Laboratory Science, Daegu Health College, Chang-ui Building, 15 Yeongsong-ro, Buk-gu, Daegu, 41453, Korea

    Tae Hee Lee

  2. Industry Academic Cooperation Foundation, Daegu Health College, 15 Yeongsong-ro, Buk-gu, Daegu, 41453, Korea

    Tae Hee Lee & Pil-Neo Hwangbo

  3. Department of Internal Medicine, Chungnam National University Sejong Hospital (CNUSH), 20, Bodeum 7-ro, Sejong, 30099, Korea

    Hong Jae Jeon

  4. Department of Biological Sciences and Bioengineering, Inha University, 100 Inha-ro, Michuhol-gu, Incheon, 22212, Korea

    Jung Hyun Choi, Hyun Sung Park, Chae Yeon Son & Jiyoon Bu

  5. School of Integrative Engineering, Chung-Ang University, Heukseok-dong, Dongjak-gu, Seoul, 06974, Korea

    Young Jun Kim

  6. Brain Korea 21 FOUR Project for Medical Science, Chungnam National University, 266, Munwha-ro, jung-gu, Daejeon, 35015, Korea

    Hei-Gwon Choi & Ha Neul Kim

  7. Department of Medical Science, Chungnam National University, 266, Munwha-ro, jung-gu, Daejeon, 35015, Korea

    Hei-Gwon Choi & Ha Neul Kim

  8. Department of Otolaryngology-Head and Neck Surgery, Research Institute for Medical Science, Chungnam National University, 266, School of Medicine, Daejeon, 35015, Korea

    Jae Won Chang

  9. Industry-Academia Interactive R&E Center for Bioprocess Innovation, Inha University, Incheon, 22212, Korea

    Jiyoon Bu

  10. Department of Internal Medicine, Chungnam National University Hospital, 282, Daejeon, 35015, Korea

    Hyuk Soo Eun

  11. Department of Internal Medicine, College of Medicine, Chungnam National University, 266, Munwha-ro, jung-gu, Daejeon, 35015, Korea

    Hyuk Soo Eun

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  1. Tae Hee Lee
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  9. Ha Neul Kim
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  11. Jiyoon Bu
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  12. Hyuk Soo Eun
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Correspondence to Jiyoon Bu or Hyuk Soo Eun.

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Lee, T.H., Jeon, H.J., Choi, J.H. et al. A high-sensitivity cfDNA capture enables to detect the BRAF V600E mutation in papillary thyroid carcinoma. Korean J. Chem. Eng. 40, 429–435 (2023). https://doi.org/10.1007/s11814-022-1348-0

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  • DOI: https://doi.org/10.1007/s11814-022-1348-0

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