Cargando…
DNA methylation fingerprint of hepatocellular carcinoma from tissue and liquid biopsies
Hepatocellular carcinoma (HCC) is amongst the cancers with highest mortality rates and is the most common malignancy of the liver. Early detection is vital to provide the best treatment possible and liquid biopsies combined with analysis of circulating tumour DNA methylation show great promise as a...
Autores principales: | , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2022
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9262906/ https://www.ncbi.nlm.nih.gov/pubmed/35798798 http://dx.doi.org/10.1038/s41598-022-15058-0 |
_version_ | 1784742602661167104 |
---|---|
author | Gonçalves, Emanuel Gonçalves-Reis, Maria Pereira-Leal, José B. Cardoso, Joana |
author_facet | Gonçalves, Emanuel Gonçalves-Reis, Maria Pereira-Leal, José B. Cardoso, Joana |
author_sort | Gonçalves, Emanuel |
collection | PubMed |
description | Hepatocellular carcinoma (HCC) is amongst the cancers with highest mortality rates and is the most common malignancy of the liver. Early detection is vital to provide the best treatment possible and liquid biopsies combined with analysis of circulating tumour DNA methylation show great promise as a non-invasive approach for early cancer diagnosis and monitoring with low false negative rates. To identify reliable diagnostic biomarkers of early HCC, we performed a systematic analysis of multiple hepatocellular studies and datasets comprising > 1500 genome-wide DNA methylation arrays, to define a methylation signature predictive of HCC in both tissue and cell-free DNA liquid biopsy samples. Our machine learning pipeline identified differentially methylated regions in HCC, some associated with transcriptional repression of genes related with cancer progression, that benchmarked positively against independent methylation signatures. Combining our signature of 38 DNA methylation regions, we derived a HCC detection score which confirmed the utility of our approach by identifying in an independent dataset 96% of HCC tissue samples with a precision of 98%, and most importantly successfully separated cfDNA of tumour samples from healthy controls. Notably, our risk score could identify cell-free DNA samples from patients with other tumours, including colorectal cancer. Taken together, we propose a comprehensive HCC DNA methylation fingerprint and an associated risk score for detection of HCC from tissue and liquid biopsies. |
format | Online Article Text |
id | pubmed-9262906 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-92629062022-07-09 DNA methylation fingerprint of hepatocellular carcinoma from tissue and liquid biopsies Gonçalves, Emanuel Gonçalves-Reis, Maria Pereira-Leal, José B. Cardoso, Joana Sci Rep Article Hepatocellular carcinoma (HCC) is amongst the cancers with highest mortality rates and is the most common malignancy of the liver. Early detection is vital to provide the best treatment possible and liquid biopsies combined with analysis of circulating tumour DNA methylation show great promise as a non-invasive approach for early cancer diagnosis and monitoring with low false negative rates. To identify reliable diagnostic biomarkers of early HCC, we performed a systematic analysis of multiple hepatocellular studies and datasets comprising > 1500 genome-wide DNA methylation arrays, to define a methylation signature predictive of HCC in both tissue and cell-free DNA liquid biopsy samples. Our machine learning pipeline identified differentially methylated regions in HCC, some associated with transcriptional repression of genes related with cancer progression, that benchmarked positively against independent methylation signatures. Combining our signature of 38 DNA methylation regions, we derived a HCC detection score which confirmed the utility of our approach by identifying in an independent dataset 96% of HCC tissue samples with a precision of 98%, and most importantly successfully separated cfDNA of tumour samples from healthy controls. Notably, our risk score could identify cell-free DNA samples from patients with other tumours, including colorectal cancer. Taken together, we propose a comprehensive HCC DNA methylation fingerprint and an associated risk score for detection of HCC from tissue and liquid biopsies. Nature Publishing Group UK 2022-07-07 /pmc/articles/PMC9262906/ /pubmed/35798798 http://dx.doi.org/10.1038/s41598-022-15058-0 Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Article Gonçalves, Emanuel Gonçalves-Reis, Maria Pereira-Leal, José B. Cardoso, Joana DNA methylation fingerprint of hepatocellular carcinoma from tissue and liquid biopsies |
title | DNA methylation fingerprint of hepatocellular carcinoma from tissue and liquid biopsies |
title_full | DNA methylation fingerprint of hepatocellular carcinoma from tissue and liquid biopsies |
title_fullStr | DNA methylation fingerprint of hepatocellular carcinoma from tissue and liquid biopsies |
title_full_unstemmed | DNA methylation fingerprint of hepatocellular carcinoma from tissue and liquid biopsies |
title_short | DNA methylation fingerprint of hepatocellular carcinoma from tissue and liquid biopsies |
title_sort | dna methylation fingerprint of hepatocellular carcinoma from tissue and liquid biopsies |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9262906/ https://www.ncbi.nlm.nih.gov/pubmed/35798798 http://dx.doi.org/10.1038/s41598-022-15058-0 |
work_keys_str_mv | AT goncalvesemanuel dnamethylationfingerprintofhepatocellularcarcinomafromtissueandliquidbiopsies AT goncalvesreismaria dnamethylationfingerprintofhepatocellularcarcinomafromtissueandliquidbiopsies AT pereiralealjoseb dnamethylationfingerprintofhepatocellularcarcinomafromtissueandliquidbiopsies AT cardosojoana dnamethylationfingerprintofhepatocellularcarcinomafromtissueandliquidbiopsies |