Cargando…
Serial circulating tumor DNA to predict early recurrence in patients with hepatocellular carcinoma: a prospective study
We studied the value of circulating tumor DNA (ctDNA) in predicting early postoperative tumor recurrence and monitoring tumor burden in patients with hepatocellular carcinoma (HCC). Plasma‐free DNA, germline DNA, and tissue DNA were isolated from 41 patients with HCC. Serial ctDNAs were analyzed by...
Autores principales: | , , , , , , , , , , , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley and Sons Inc.
2021
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8763657/ https://www.ncbi.nlm.nih.gov/pubmed/34543520 http://dx.doi.org/10.1002/1878-0261.13105 |
_version_ | 1784633995823153152 |
---|---|
author | Zhu, Gui‐Qi Liu, Wei‐Ren Tang, Zheng Qu, Wei‐Feng Fang, Yuan Jiang, Xi‐Fei Song, Shu‐Shu Wang, Han Tao, Chen‐Yang Zhou, Pei‐Yun Huang, Run Gao, Jun Sun, Hai‐Xiang Ding, Zhen‐Bin Peng, Yuan‐Fei Dai, Zhi Zhou, Jian Fan, Jia Shi, Ying‐Hong |
author_facet | Zhu, Gui‐Qi Liu, Wei‐Ren Tang, Zheng Qu, Wei‐Feng Fang, Yuan Jiang, Xi‐Fei Song, Shu‐Shu Wang, Han Tao, Chen‐Yang Zhou, Pei‐Yun Huang, Run Gao, Jun Sun, Hai‐Xiang Ding, Zhen‐Bin Peng, Yuan‐Fei Dai, Zhi Zhou, Jian Fan, Jia Shi, Ying‐Hong |
author_sort | Zhu, Gui‐Qi |
collection | PubMed |
description | We studied the value of circulating tumor DNA (ctDNA) in predicting early postoperative tumor recurrence and monitoring tumor burden in patients with hepatocellular carcinoma (HCC). Plasma‐free DNA, germline DNA, and tissue DNA were isolated from 41 patients with HCC. Serial ctDNAs were analyzed by next‐generation sequencing before and after operation. Whole‐exome sequencing was used to detect the DNA of HCC and adjacent tissues. In total, 47 gene mutations were identified in the ctDNA of the 41 patients analyzed before surgery. ctDNA was detected in 63.4% and 46% of the patient plasma pre‐ and postoperation, respectively. The preoperative ctDNA positivity rate was significantly lower in the nonrecurrence group than in the recurrence group. With a median follow‐up of 17.7 months, nine patients (22%) experienced tumor recurrence. ctDNA positivity at two time‐points was associated with significantly shorter recurrence‐free survival (RFS). Tumors with NRAS, NEF2L2, and MET mutations had significantly shorter times to recurrence than those without mutations and showed high recurrence prediction performance by machine learning. Multivariate analyses showed that the median variant allele frequency (VAF) of mutations in preoperative ctDNA was a strong independent predictor of RFS. ctDNA is a real‐time monitoring indicator that can accurately reflect tumor burden. The median VAF of baseline ctDNA is a strong independent predictor of RFS in individuals with HCC. |
format | Online Article Text |
id | pubmed-8763657 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-87636572022-01-21 Serial circulating tumor DNA to predict early recurrence in patients with hepatocellular carcinoma: a prospective study Zhu, Gui‐Qi Liu, Wei‐Ren Tang, Zheng Qu, Wei‐Feng Fang, Yuan Jiang, Xi‐Fei Song, Shu‐Shu Wang, Han Tao, Chen‐Yang Zhou, Pei‐Yun Huang, Run Gao, Jun Sun, Hai‐Xiang Ding, Zhen‐Bin Peng, Yuan‐Fei Dai, Zhi Zhou, Jian Fan, Jia Shi, Ying‐Hong Mol Oncol Research Articles We studied the value of circulating tumor DNA (ctDNA) in predicting early postoperative tumor recurrence and monitoring tumor burden in patients with hepatocellular carcinoma (HCC). Plasma‐free DNA, germline DNA, and tissue DNA were isolated from 41 patients with HCC. Serial ctDNAs were analyzed by next‐generation sequencing before and after operation. Whole‐exome sequencing was used to detect the DNA of HCC and adjacent tissues. In total, 47 gene mutations were identified in the ctDNA of the 41 patients analyzed before surgery. ctDNA was detected in 63.4% and 46% of the patient plasma pre‐ and postoperation, respectively. The preoperative ctDNA positivity rate was significantly lower in the nonrecurrence group than in the recurrence group. With a median follow‐up of 17.7 months, nine patients (22%) experienced tumor recurrence. ctDNA positivity at two time‐points was associated with significantly shorter recurrence‐free survival (RFS). Tumors with NRAS, NEF2L2, and MET mutations had significantly shorter times to recurrence than those without mutations and showed high recurrence prediction performance by machine learning. Multivariate analyses showed that the median variant allele frequency (VAF) of mutations in preoperative ctDNA was a strong independent predictor of RFS. ctDNA is a real‐time monitoring indicator that can accurately reflect tumor burden. The median VAF of baseline ctDNA is a strong independent predictor of RFS in individuals with HCC. John Wiley and Sons Inc. 2021-10-04 2022-01 /pmc/articles/PMC8763657/ /pubmed/34543520 http://dx.doi.org/10.1002/1878-0261.13105 Text en © 2021 The Authors. Molecular Oncology published by John Wiley & Sons Ltd on behalf of Federation of European Biochemical Societies. https://creativecommons.org/licenses/by/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Research Articles Zhu, Gui‐Qi Liu, Wei‐Ren Tang, Zheng Qu, Wei‐Feng Fang, Yuan Jiang, Xi‐Fei Song, Shu‐Shu Wang, Han Tao, Chen‐Yang Zhou, Pei‐Yun Huang, Run Gao, Jun Sun, Hai‐Xiang Ding, Zhen‐Bin Peng, Yuan‐Fei Dai, Zhi Zhou, Jian Fan, Jia Shi, Ying‐Hong Serial circulating tumor DNA to predict early recurrence in patients with hepatocellular carcinoma: a prospective study |
title | Serial circulating tumor DNA to predict early recurrence in patients with hepatocellular carcinoma: a prospective study |
title_full | Serial circulating tumor DNA to predict early recurrence in patients with hepatocellular carcinoma: a prospective study |
title_fullStr | Serial circulating tumor DNA to predict early recurrence in patients with hepatocellular carcinoma: a prospective study |
title_full_unstemmed | Serial circulating tumor DNA to predict early recurrence in patients with hepatocellular carcinoma: a prospective study |
title_short | Serial circulating tumor DNA to predict early recurrence in patients with hepatocellular carcinoma: a prospective study |
title_sort | serial circulating tumor dna to predict early recurrence in patients with hepatocellular carcinoma: a prospective study |
topic | Research Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8763657/ https://www.ncbi.nlm.nih.gov/pubmed/34543520 http://dx.doi.org/10.1002/1878-0261.13105 |
work_keys_str_mv | AT zhuguiqi serialcirculatingtumordnatopredictearlyrecurrenceinpatientswithhepatocellularcarcinomaaprospectivestudy AT liuweiren serialcirculatingtumordnatopredictearlyrecurrenceinpatientswithhepatocellularcarcinomaaprospectivestudy AT tangzheng serialcirculatingtumordnatopredictearlyrecurrenceinpatientswithhepatocellularcarcinomaaprospectivestudy AT quweifeng serialcirculatingtumordnatopredictearlyrecurrenceinpatientswithhepatocellularcarcinomaaprospectivestudy AT fangyuan serialcirculatingtumordnatopredictearlyrecurrenceinpatientswithhepatocellularcarcinomaaprospectivestudy AT jiangxifei serialcirculatingtumordnatopredictearlyrecurrenceinpatientswithhepatocellularcarcinomaaprospectivestudy AT songshushu serialcirculatingtumordnatopredictearlyrecurrenceinpatientswithhepatocellularcarcinomaaprospectivestudy AT wanghan serialcirculatingtumordnatopredictearlyrecurrenceinpatientswithhepatocellularcarcinomaaprospectivestudy AT taochenyang serialcirculatingtumordnatopredictearlyrecurrenceinpatientswithhepatocellularcarcinomaaprospectivestudy AT zhoupeiyun serialcirculatingtumordnatopredictearlyrecurrenceinpatientswithhepatocellularcarcinomaaprospectivestudy AT huangrun serialcirculatingtumordnatopredictearlyrecurrenceinpatientswithhepatocellularcarcinomaaprospectivestudy AT gaojun serialcirculatingtumordnatopredictearlyrecurrenceinpatientswithhepatocellularcarcinomaaprospectivestudy AT sunhaixiang serialcirculatingtumordnatopredictearlyrecurrenceinpatientswithhepatocellularcarcinomaaprospectivestudy AT dingzhenbin serialcirculatingtumordnatopredictearlyrecurrenceinpatientswithhepatocellularcarcinomaaprospectivestudy AT pengyuanfei serialcirculatingtumordnatopredictearlyrecurrenceinpatientswithhepatocellularcarcinomaaprospectivestudy AT daizhi serialcirculatingtumordnatopredictearlyrecurrenceinpatientswithhepatocellularcarcinomaaprospectivestudy AT zhoujian serialcirculatingtumordnatopredictearlyrecurrenceinpatientswithhepatocellularcarcinomaaprospectivestudy AT fanjia serialcirculatingtumordnatopredictearlyrecurrenceinpatientswithhepatocellularcarcinomaaprospectivestudy AT shiyinghong serialcirculatingtumordnatopredictearlyrecurrenceinpatientswithhepatocellularcarcinomaaprospectivestudy |