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...
| Main Authors: | , , , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Wiley
2022-01-01
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| Series: | Molecular Oncology |
| Subjects: | |
| Online Access: | https://doi.org/10.1002/1878-0261.13105 |
| _version_ | 1828137348360044544 |
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| author | Gui‐Qi Zhu Wei‐Ren Liu Zheng Tang Wei‐Feng Qu Yuan Fang Xi‐Fei Jiang Shu‐Shu Song Han Wang Chen‐Yang Tao Pei‐Yun Zhou Run Huang Jun Gao Hai‐Xiang Sun Zhen‐Bin Ding Yuan‐Fei Peng Zhi Dai Jian Zhou Jia Fan Ying‐Hong Shi |
| author_facet | Gui‐Qi Zhu Wei‐Ren Liu Zheng Tang Wei‐Feng Qu Yuan Fang Xi‐Fei Jiang Shu‐Shu Song Han Wang Chen‐Yang Tao Pei‐Yun Zhou Run Huang Jun Gao Hai‐Xiang Sun Zhen‐Bin Ding Yuan‐Fei Peng Zhi Dai Jian Zhou Jia Fan Ying‐Hong Shi |
| author_sort | Gui‐Qi Zhu |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-04-11T18:18:26Z |
| format | Article |
| id | doaj.art-0f0f594949d142c2a9e6bcccf170d330 |
| institution | Directory Open Access Journal |
| issn | 1574-7891 1878-0261 |
| language | English |
| last_indexed | 2024-04-11T18:18:26Z |
| publishDate | 2022-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Molecular Oncology |
| spelling | doaj.art-0f0f594949d142c2a9e6bcccf170d3302022-12-22T04:09:50ZengWileyMolecular Oncology1574-78911878-02612022-01-0116254956110.1002/1878-0261.13105Serial circulating tumor DNA to predict early recurrence in patients with hepatocellular carcinoma: a prospective studyGui‐Qi Zhu0Wei‐Ren Liu1Zheng Tang2Wei‐Feng Qu3Yuan Fang4Xi‐Fei Jiang5Shu‐Shu Song6Han Wang7Chen‐Yang Tao8Pei‐Yun Zhou9Run Huang10Jun Gao11Hai‐Xiang Sun12Zhen‐Bin Ding13Yuan‐Fei Peng14Zhi Dai15Jian Zhou16Jia Fan17Ying‐Hong Shi18Department of Liver Surgery and Transplantation Liver Cancer Institute Zhongshan Hospital Fudan University Shanghai ChinaDepartment of Liver Surgery and Transplantation Liver Cancer Institute Zhongshan Hospital Fudan University Shanghai ChinaDepartment of Liver Surgery and Transplantation Liver Cancer Institute Zhongshan Hospital Fudan University Shanghai ChinaDepartment of Liver Surgery and Transplantation Liver Cancer Institute Zhongshan Hospital Fudan University Shanghai ChinaDepartment of Liver Surgery and Transplantation Liver Cancer Institute Zhongshan Hospital Fudan University Shanghai ChinaDepartment of Liver Surgery and Transplantation Liver Cancer Institute Zhongshan Hospital Fudan University Shanghai ChinaDepartment of Liver Surgery and Transplantation Liver Cancer Institute Zhongshan Hospital Fudan University Shanghai ChinaDepartment of Liver Surgery and Transplantation Liver Cancer Institute Zhongshan Hospital Fudan University Shanghai ChinaDepartment of Liver Surgery and Transplantation Liver Cancer Institute Zhongshan Hospital Fudan University Shanghai ChinaDepartment of Liver Surgery and Transplantation Liver Cancer Institute Zhongshan Hospital Fudan University Shanghai ChinaDepartment of Liver Surgery and Transplantation Liver Cancer Institute Zhongshan Hospital Fudan University Shanghai ChinaDepartment of Liver Surgery and Transplantation Liver Cancer Institute Zhongshan Hospital Fudan University Shanghai ChinaDepartment of Liver Surgery and Transplantation Liver Cancer Institute Zhongshan Hospital Fudan University Shanghai ChinaDepartment of Liver Surgery and Transplantation Liver Cancer Institute Zhongshan Hospital Fudan University Shanghai ChinaDepartment of Liver Surgery and Transplantation Liver Cancer Institute Zhongshan Hospital Fudan University Shanghai ChinaDepartment of Liver Surgery and Transplantation Liver Cancer Institute Zhongshan Hospital Fudan University Shanghai ChinaDepartment of Liver Surgery and Transplantation Liver Cancer Institute Zhongshan Hospital Fudan University Shanghai ChinaDepartment of Liver Surgery and Transplantation Liver Cancer Institute Zhongshan Hospital Fudan University Shanghai ChinaDepartment of Liver Surgery and Transplantation Liver Cancer Institute Zhongshan Hospital Fudan University Shanghai ChinaWe 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.https://doi.org/10.1002/1878-0261.13105biomarkerctDNAhepatocellular carcinomatumor recurrence |
| spellingShingle | Gui‐Qi Zhu Wei‐Ren Liu Zheng Tang Wei‐Feng Qu Yuan Fang Xi‐Fei Jiang Shu‐Shu Song Han Wang Chen‐Yang Tao Pei‐Yun Zhou Run Huang Jun Gao Hai‐Xiang Sun Zhen‐Bin Ding Yuan‐Fei Peng Zhi Dai Jian Zhou Jia Fan Ying‐Hong Shi Serial circulating tumor DNA to predict early recurrence in patients with hepatocellular carcinoma: a prospective study Molecular Oncology biomarker ctDNA hepatocellular carcinoma tumor recurrence |
| 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 | biomarker ctDNA hepatocellular carcinoma tumor recurrence |
| url | https://doi.org/10.1002/1878-0261.13105 |
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