Machine-Learning-Based Clinical Biomarker Using Cell-Free DNA for Hepatocellular Carcinoma (HCC)

(1) Background: Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related death worldwide. Although various serum enzymes have been utilized for the diagnosis and prognosis of HCC, the currently available biomarkers lack the sensitivity needed to detect HCC at early stages and ac...

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Main Authors: Taehee Lee, Piper A. Rawding, Jiyoon Bu, Sunghee Hyun, Woosun Rou, Hongjae Jeon, Seokhyun Kim, Byungseok Lee, Luke J. Kubiatowicz, Dawon Kim, Seungpyo Hong, Hyuksoo Eun
Format: Article
Language:English
Published: MDPI AG 2022-04-01
Series:Cancers
Subjects:
Online Access:https://www.mdpi.com/2072-6694/14/9/2061
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author Taehee Lee
Piper A. Rawding
Jiyoon Bu
Sunghee Hyun
Woosun Rou
Hongjae Jeon
Seokhyun Kim
Byungseok Lee
Luke J. Kubiatowicz
Dawon Kim
Seungpyo Hong
Hyuksoo Eun
author_facet Taehee Lee
Piper A. Rawding
Jiyoon Bu
Sunghee Hyun
Woosun Rou
Hongjae Jeon
Seokhyun Kim
Byungseok Lee
Luke J. Kubiatowicz
Dawon Kim
Seungpyo Hong
Hyuksoo Eun
author_sort Taehee Lee
collection DOAJ
description (1) Background: Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related death worldwide. Although various serum enzymes have been utilized for the diagnosis and prognosis of HCC, the currently available biomarkers lack the sensitivity needed to detect HCC at early stages and accurately predict treatment responses. (2) Methods: We utilized our highly sensitive cell-free DNA (cfDNA) detection system, in combination with a machine learning algorithm, to provide a platform for improved diagnosis and prognosis of HCC. (3) Results: cfDNA, specifically alpha-fetoprotein (AFP) expression in captured cfDNA, demonstrated the highest accuracy for diagnosing malignancies among the serum/plasma biomarkers used in this study, including AFP, aspartate aminotransferase, alanine aminotransferase, albumin, alkaline phosphatase, and bilirubin. The diagnostic/prognostic capability of cfDNA was further improved by establishing a cfDNA score (cfD<sub>HCC</sub>), which integrated the total plasma cfDNA levels and cfAFP-DNA expression into a single score using machine learning algorithms. (4) Conclusion: The cfD<sub>HCC</sub> score demonstrated significantly improved accuracy in determining the pathological features of HCC and predicting patients’ survival outcomes compared to the other biomarkers. The results presented herein reveal that our cfDNA capture/analysis platform is a promising approach to effectively utilize cfDNA as a biomarker for the diagnosis and prognosis of HCC.
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spelling doaj.art-94e9c802e55f480c8b8d02968456b43d2023-11-23T07:54:19ZengMDPI AGCancers2072-66942022-04-01149206110.3390/cancers14092061Machine-Learning-Based Clinical Biomarker Using Cell-Free DNA for Hepatocellular Carcinoma (HCC)Taehee Lee0Piper A. Rawding1Jiyoon Bu2Sunghee Hyun3Woosun Rou4Hongjae Jeon5Seokhyun Kim6Byungseok Lee7Luke J. Kubiatowicz8Dawon Kim9Seungpyo Hong10Hyuksoo Eun11Department of Biomedical Laboratory Science, Daegu Health College, Daegu 41453, KoreaPharmaceutical Sciences Division, School of Pharmacy, University of Wisconsin—Madison, Madison, WI 53705, USAPharmaceutical Sciences Division, School of Pharmacy, University of Wisconsin—Madison, Madison, WI 53705, USADepartment of Senior Healthcare, Graduate School, Eulji University, Uijeongbu-si 11759, KoreaDepartment of Internal Medicine, Chungnam National University Sejong Hospital (CNUSH), Sejong 30099, KoreaDepartment of Internal Medicine, Chungnam National University Sejong Hospital (CNUSH), Sejong 30099, KoreaDepartment of Internal Medicine, Chungnam National University Hospital, Daejeon 35015, KoreaDepartment of Internal Medicine, Chungnam National University Hospital, Daejeon 35015, KoreaPharmaceutical Sciences Division, School of Pharmacy, University of Wisconsin—Madison, Madison, WI 53705, USAPharmaceutical Sciences Division, School of Pharmacy, University of Wisconsin—Madison, Madison, WI 53705, USAPharmaceutical Sciences Division, School of Pharmacy, University of Wisconsin—Madison, Madison, WI 53705, USADepartment of Internal Medicine, Chungnam National University Hospital, Daejeon 35015, Korea(1) Background: Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related death worldwide. Although various serum enzymes have been utilized for the diagnosis and prognosis of HCC, the currently available biomarkers lack the sensitivity needed to detect HCC at early stages and accurately predict treatment responses. (2) Methods: We utilized our highly sensitive cell-free DNA (cfDNA) detection system, in combination with a machine learning algorithm, to provide a platform for improved diagnosis and prognosis of HCC. (3) Results: cfDNA, specifically alpha-fetoprotein (AFP) expression in captured cfDNA, demonstrated the highest accuracy for diagnosing malignancies among the serum/plasma biomarkers used in this study, including AFP, aspartate aminotransferase, alanine aminotransferase, albumin, alkaline phosphatase, and bilirubin. The diagnostic/prognostic capability of cfDNA was further improved by establishing a cfDNA score (cfD<sub>HCC</sub>), which integrated the total plasma cfDNA levels and cfAFP-DNA expression into a single score using machine learning algorithms. (4) Conclusion: The cfD<sub>HCC</sub> score demonstrated significantly improved accuracy in determining the pathological features of HCC and predicting patients’ survival outcomes compared to the other biomarkers. The results presented herein reveal that our cfDNA capture/analysis platform is a promising approach to effectively utilize cfDNA as a biomarker for the diagnosis and prognosis of HCC.https://www.mdpi.com/2072-6694/14/9/2061cell-free DNA (cfDNA)circulating tumor DNA (ctDNA)hepatocellular carcinoma (HCC)liquid biopsyprincipal component analysis (PCA)
spellingShingle Taehee Lee
Piper A. Rawding
Jiyoon Bu
Sunghee Hyun
Woosun Rou
Hongjae Jeon
Seokhyun Kim
Byungseok Lee
Luke J. Kubiatowicz
Dawon Kim
Seungpyo Hong
Hyuksoo Eun
Machine-Learning-Based Clinical Biomarker Using Cell-Free DNA for Hepatocellular Carcinoma (HCC)
Cancers
cell-free DNA (cfDNA)
circulating tumor DNA (ctDNA)
hepatocellular carcinoma (HCC)
liquid biopsy
principal component analysis (PCA)
title Machine-Learning-Based Clinical Biomarker Using Cell-Free DNA for Hepatocellular Carcinoma (HCC)
title_full Machine-Learning-Based Clinical Biomarker Using Cell-Free DNA for Hepatocellular Carcinoma (HCC)
title_fullStr Machine-Learning-Based Clinical Biomarker Using Cell-Free DNA for Hepatocellular Carcinoma (HCC)
title_full_unstemmed Machine-Learning-Based Clinical Biomarker Using Cell-Free DNA for Hepatocellular Carcinoma (HCC)
title_short Machine-Learning-Based Clinical Biomarker Using Cell-Free DNA for Hepatocellular Carcinoma (HCC)
title_sort machine learning based clinical biomarker using cell free dna for hepatocellular carcinoma hcc
topic cell-free DNA (cfDNA)
circulating tumor DNA (ctDNA)
hepatocellular carcinoma (HCC)
liquid biopsy
principal component analysis (PCA)
url https://www.mdpi.com/2072-6694/14/9/2061
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