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Investigation on the potential of circulating tumor DNA methylation patterns as prognostic biomarkers for lung squamous cell carcinoma
BACKGROUND: Aberrant epigenetic modifications play a key role in lung tumorigenesis. In our study, we aimed to explore the clinical implications of baseline circulating tumor DNA (ctDNA) somatic and methylation profiles in patients with lung squamous cell carcinoma (LUSC). METHODS: A total of 26 pat...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
AME Publishing Company
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7815356/ https://www.ncbi.nlm.nih.gov/pubmed/33489798 http://dx.doi.org/10.21037/tlcr-20-1070 |
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author | Liu, Yutao Feng, Yu Hou, Ting Lizaso, Analyn Xu, Feng Xing, Puyuan Wang, Hongyu Kang, Qiaolin Zhang, Lu Shi, Yuankai Hu, Xingsheng |
author_facet | Liu, Yutao Feng, Yu Hou, Ting Lizaso, Analyn Xu, Feng Xing, Puyuan Wang, Hongyu Kang, Qiaolin Zhang, Lu Shi, Yuankai Hu, Xingsheng |
author_sort | Liu, Yutao |
collection | PubMed |
description | BACKGROUND: Aberrant epigenetic modifications play a key role in lung tumorigenesis. In our study, we aimed to explore the clinical implications of baseline circulating tumor DNA (ctDNA) somatic and methylation profiles in patients with lung squamous cell carcinoma (LUSC). METHODS: A total of 26 patients with LUSC of various stages were included in this study. Somatic mutations and methylation levels were profiled from the plasma-derived ctDNA obtained at the time of diagnosis using unique molecular identifier (UMI)-based targeted sequencing and bisulfite sequencing, respectively. The correlation between baseline ctDNA mutation and methylation profile, and overall survival (OS), were analyzed. RESULTS: Somatic mutations were detected in 80.8% (20/26) of the patients. Patients harboring somatic mutations with maximum allelic fraction (maxAF) of >5% had significantly shorter OS compared to those with maxAF ≤5% (7.1 vs. 54.6 months; P=0.020). ctDNA methylation level was found to be strongly correlated with maxAF (Pearson correlation =0.934; P<0.001). Consistent with maxAF, higher methylation levels were also associated with poorer OS (hazard ratio =2.377; 95% CI: 1.283–4.405; P=0.006). Moreover, a total of 1,956 ctDNA methylation blocks were differentially methylated in patients with maxAF >0 (P<0.05). Least absolute shrinkage and selection operator (LASSO) regression analysis revealed a significant correlation between methylation signatures from 5 methylation blocks and OS (hazard ratio =183.20, 95% CI: 2.74–12,243.32; P=0.015). These 5 methylation blocks could serve as an alternative to maxAF and can be explored as prognostic biomarkers. CONCLUSIONS: Our study identified several ctDNA methylation blocks that can potentially predict the prognosis of LUSC at the time of diagnosis. |
format | Online Article Text |
id | pubmed-7815356 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | AME Publishing Company |
record_format | MEDLINE/PubMed |
spelling | pubmed-78153562021-01-22 Investigation on the potential of circulating tumor DNA methylation patterns as prognostic biomarkers for lung squamous cell carcinoma Liu, Yutao Feng, Yu Hou, Ting Lizaso, Analyn Xu, Feng Xing, Puyuan Wang, Hongyu Kang, Qiaolin Zhang, Lu Shi, Yuankai Hu, Xingsheng Transl Lung Cancer Res Original Article BACKGROUND: Aberrant epigenetic modifications play a key role in lung tumorigenesis. In our study, we aimed to explore the clinical implications of baseline circulating tumor DNA (ctDNA) somatic and methylation profiles in patients with lung squamous cell carcinoma (LUSC). METHODS: A total of 26 patients with LUSC of various stages were included in this study. Somatic mutations and methylation levels were profiled from the plasma-derived ctDNA obtained at the time of diagnosis using unique molecular identifier (UMI)-based targeted sequencing and bisulfite sequencing, respectively. The correlation between baseline ctDNA mutation and methylation profile, and overall survival (OS), were analyzed. RESULTS: Somatic mutations were detected in 80.8% (20/26) of the patients. Patients harboring somatic mutations with maximum allelic fraction (maxAF) of >5% had significantly shorter OS compared to those with maxAF ≤5% (7.1 vs. 54.6 months; P=0.020). ctDNA methylation level was found to be strongly correlated with maxAF (Pearson correlation =0.934; P<0.001). Consistent with maxAF, higher methylation levels were also associated with poorer OS (hazard ratio =2.377; 95% CI: 1.283–4.405; P=0.006). Moreover, a total of 1,956 ctDNA methylation blocks were differentially methylated in patients with maxAF >0 (P<0.05). Least absolute shrinkage and selection operator (LASSO) regression analysis revealed a significant correlation between methylation signatures from 5 methylation blocks and OS (hazard ratio =183.20, 95% CI: 2.74–12,243.32; P=0.015). These 5 methylation blocks could serve as an alternative to maxAF and can be explored as prognostic biomarkers. CONCLUSIONS: Our study identified several ctDNA methylation blocks that can potentially predict the prognosis of LUSC at the time of diagnosis. AME Publishing Company 2020-12 /pmc/articles/PMC7815356/ /pubmed/33489798 http://dx.doi.org/10.21037/tlcr-20-1070 Text en 2020 Translational Lung Cancer Research. All rights reserved. https://creativecommons.org/licenses/by-nc-nd/4.0/Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0 (https://creativecommons.org/licenses/by-nc-nd/4.0/) . |
spellingShingle | Original Article Liu, Yutao Feng, Yu Hou, Ting Lizaso, Analyn Xu, Feng Xing, Puyuan Wang, Hongyu Kang, Qiaolin Zhang, Lu Shi, Yuankai Hu, Xingsheng Investigation on the potential of circulating tumor DNA methylation patterns as prognostic biomarkers for lung squamous cell carcinoma |
title | Investigation on the potential of circulating tumor DNA methylation patterns as prognostic biomarkers for lung squamous cell carcinoma |
title_full | Investigation on the potential of circulating tumor DNA methylation patterns as prognostic biomarkers for lung squamous cell carcinoma |
title_fullStr | Investigation on the potential of circulating tumor DNA methylation patterns as prognostic biomarkers for lung squamous cell carcinoma |
title_full_unstemmed | Investigation on the potential of circulating tumor DNA methylation patterns as prognostic biomarkers for lung squamous cell carcinoma |
title_short | Investigation on the potential of circulating tumor DNA methylation patterns as prognostic biomarkers for lung squamous cell carcinoma |
title_sort | investigation on the potential of circulating tumor dna methylation patterns as prognostic biomarkers for lung squamous cell carcinoma |
topic | Original Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7815356/ https://www.ncbi.nlm.nih.gov/pubmed/33489798 http://dx.doi.org/10.21037/tlcr-20-1070 |
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