Cell-free DNA testing for early hepatocellular carcinoma surveillanceResearch in context
Summary: Background: Liver cirrhosis (LC) is the highest risk factor for hepatocellular carcinoma (HCC) development worldwide. The efficacy of the guideline-recommended surveillance methods for patients with LC remains unpromising. Methods: A total of 4367 LCs not previously known to have HCC and 5...
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| Language: | English |
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Elsevier
2024-02-01
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| Series: | EBioMedicine |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2352396423005285 |
| _version_ | 1797362667622498304 |
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| author | Lei Chen Tong Wu Rong Fan Yun-Song Qian Jing-Feng Liu Jian Bai Bo Zheng Xiao-Long Liu Dan Zheng Lu-Tao Du Guo-Qing Jiang Ying-Chao Wang Xiao-Tang Fan Guo-Hong Deng Chun-Ying Wang Feng Shen He-Ping Hu Qing-Zheng Zhang Yi-Nong Ye Jing Zhang Yan-Hang Gao Jie Xia Hua-Dong Yan Min-Feng Liang Yan-Long Yu Fu-Ming Sun Yu-Jing Gao Jian Sun Chun-Xiu Zhong Yin Wang Hui Wang Fei Kong Jin-Ming Chen Hao Wen Bo-Ming Wu Chuan-Xin Wang Lin Wu Jin-Lin Hou Hong-Yang Wang |
| author_facet | Lei Chen Tong Wu Rong Fan Yun-Song Qian Jing-Feng Liu Jian Bai Bo Zheng Xiao-Long Liu Dan Zheng Lu-Tao Du Guo-Qing Jiang Ying-Chao Wang Xiao-Tang Fan Guo-Hong Deng Chun-Ying Wang Feng Shen He-Ping Hu Qing-Zheng Zhang Yi-Nong Ye Jing Zhang Yan-Hang Gao Jie Xia Hua-Dong Yan Min-Feng Liang Yan-Long Yu Fu-Ming Sun Yu-Jing Gao Jian Sun Chun-Xiu Zhong Yin Wang Hui Wang Fei Kong Jin-Ming Chen Hao Wen Bo-Ming Wu Chuan-Xin Wang Lin Wu Jin-Lin Hou Hong-Yang Wang |
| author_sort | Lei Chen |
| collection | DOAJ |
| description | Summary: Background: Liver cirrhosis (LC) is the highest risk factor for hepatocellular carcinoma (HCC) development worldwide. The efficacy of the guideline-recommended surveillance methods for patients with LC remains unpromising. Methods: A total of 4367 LCs not previously known to have HCC and 510 HCCs from 16 hospitals across 11 provinces of China were recruited in this multi-center, large-scale, cross-sectional study. Participants were divided into Stage Ⅰ cohort (510 HCCs and 2074 LCs) and Stage Ⅱ cohort (2293 LCs) according to their enrollment time and underwent Tri-phasic CT/enhanced MRI, US, AFP, and cell-free DNA (cfDNA). A screening model called PreCar Score was established based on five features of cfDNA using Stage Ⅰ cohort. Surveillance performance of PreCar Score alone or in combination with US/AFP was evaluated in Stage Ⅱ cohort. Findings: PreCar Score showed a significantly higher sensitivity for the detection of early/very early HCC (Barcelona stage A/0) in contrast to US (sensitivity of 51.32% [95% CI: 39.66%–62.84%] at 95.53% [95% CI: 94.62%–96.38%] specificity for PreCar Score; sensitivity of 23.68% [95% CI: 14.99%–35.07%] at 99.37% [95% CI: 98.91%–99.64%] specificity for US) (P < 0.01, Fisher's exact test). PreCar Score plus US further achieved a higher sensitivity of 60.53% at 95.08% specificity for early/very early HCC screening. Interpretation: Our study developed and validated a cfDNA-based screening tool (PreCar Score) for HCC in cohorts at high risk. The combination of PreCar Score and US can serve as a promising and practical strategy for routine HCC care. Funding: A full list of funding bodies that contributed to this study can be found in Acknowledgments section. |
| first_indexed | 2024-03-08T16:09:43Z |
| format | Article |
| id | doaj.art-c0d3e58de63f4892bd2870d9cfb7c472 |
| institution | Directory Open Access Journal |
| issn | 2352-3964 |
| language | English |
| last_indexed | 2024-03-08T16:09:43Z |
| publishDate | 2024-02-01 |
| publisher | Elsevier |
| record_format | Article |
| series | EBioMedicine |
| spelling | doaj.art-c0d3e58de63f4892bd2870d9cfb7c4722024-01-08T04:07:51ZengElsevierEBioMedicine2352-39642024-02-01100104962Cell-free DNA testing for early hepatocellular carcinoma surveillanceResearch in contextLei Chen0Tong Wu1Rong Fan2Yun-Song Qian3Jing-Feng Liu4Jian Bai5Bo Zheng6Xiao-Long Liu7Dan Zheng8Lu-Tao Du9Guo-Qing Jiang10Ying-Chao Wang11Xiao-Tang Fan12Guo-Hong Deng13Chun-Ying Wang14Feng Shen15He-Ping Hu16Qing-Zheng Zhang17Yi-Nong Ye18Jing Zhang19Yan-Hang Gao20Jie Xia21Hua-Dong Yan22Min-Feng Liang23Yan-Long Yu24Fu-Ming Sun25Yu-Jing Gao26Jian Sun27Chun-Xiu Zhong28Yin Wang29Hui Wang30Fei Kong31Jin-Ming Chen32Hao Wen33Bo-Ming Wu34Chuan-Xin Wang35Lin Wu36Jin-Lin Hou37Hong-Yang Wang38National Center of Liver Cancer, Navel Medical University, Shanghai, 210822, PR China; International Cooperation Laboratory on Signal Transduction, Eastern Hepatobiliary Surgery Institute/Hospital, Shanghai, 200438, PR China; Corresponding author. International Co-operation Laboratory on Signal Transduction, Eastern Hepatobiliary Surgery Institute/Hospital, Shanghai, 200438, PR China.National Center of Liver Cancer, Navel Medical University, Shanghai, 210822, PR China; Department of Radiation Oncology, General Hospital of Northern Theater Command, Shenyang, l10016, PR ChinaDepartment of Infectious Diseases, State Key Laboratory of Organ Failure Research, Guangdong Provincial Key Laboratory of Viral Hepatitis Research, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, PR China; Hepatology Unit, Shenzhen Hospital, Southern Medical University, Shenzhen, PR ChinaHepatology Department, Ningbo Hwamei Hospital, University of Chinese Academy of Sciences, Ningbo, 315010, PR ChinaThe United Innovation of Mengchao Hepatobiliary Technology Key Laboratory of Fujian Province, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou, 350025, PR ChinaBerry Oncology Corporation, Beijing, 100102, PR ChinaNational Center of Liver Cancer, Navel Medical University, Shanghai, 210822, PR China; International Cooperation Laboratory on Signal Transduction, Eastern Hepatobiliary Surgery Institute/Hospital, Shanghai, 200438, PR ChinaThe United Innovation of Mengchao Hepatobiliary Technology Key Laboratory of Fujian Province, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou, 350025, PR ChinaDepartment of Gastroenterology, The Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430014, PR ChinaDepartment of Clinical Laboratory, The Second Hospital, Cheeloo College of Medicine, Shandong University, 247 Beiyuan Street, Jinan 250033, Shandong, PR China; Shandong Provincial Clinical Medicine Research Center for Clinical Laboratory, Jinan, 250033, PR ChinaDepartment of Hepatobiliary Surgery, Clinical Medical College, Yangzhou University, Yangzhou, 225001, PR ChinaThe United Innovation of Mengchao Hepatobiliary Technology Key Laboratory of Fujian Province, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou, 350025, PR ChinaDepartment of Hepatology, First Affiliated Hospital of Xinjiang Medical University, Urumqi, 830000, PR ChinaDepartment of Infectious Diseases, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing, 400038, PR ChinaXuzhou Infectious Diseases Hospital, Xuzhou, 221004, PR ChinaDepartment of Hepatic Surgery IV, Eastern Hepatobiliary Surgery Institute, Second Military Medical University, Shanghai, 200438, PR ChinaDepartment of Hepatobiliary Medicine, Shanghai Eastern Hepatobiliary Surgery Hospital, Shanghai, 210822, PR ChinaBerry Oncology Corporation, Beijing, 100102, PR ChinaThe Department of Infectious Disease, The First People's Hospital of Foshan, Foshan City, 528000, PR ChinaBerry Oncology Corporation, Beijing, 100102, PR ChinaThe First Hospital of Jilin University, Jilin, 130021, PR ChinaDepartment of Infectious Diseases, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing, 400038, PR ChinaHepatology Department, Ningbo Hwamei Hospital, University of Chinese Academy of Sciences, Ningbo, 315010, PR ChinaThe Department of Infectious Disease, The First People's Hospital of Foshan, Foshan City, 528000, PR ChinaChifeng Clinical Medical School of Inner Mongolia Medical University, Chifeng, 024000, PR ChinaBerry Oncology Corporation, Beijing, 100102, PR ChinaXuzhou Infectious Diseases Hospital, Xuzhou, 221004, PR ChinaDepartment of Infectious Diseases, State Key Laboratory of Organ Failure Research, Guangdong Provincial Key Laboratory of Viral Hepatitis Research, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, PR ChinaDepartment of Infectious Diseases, State Key Laboratory of Organ Failure Research, Guangdong Provincial Key Laboratory of Viral Hepatitis Research, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, PR ChinaBerry Oncology Corporation, Beijing, 100102, PR ChinaDepartment of Hepatobiliary Medicine, Shanghai Eastern Hepatobiliary Surgery Hospital, Shanghai, 210822, PR ChinaThe First Hospital of Jilin University, Jilin, 130021, PR ChinaChifeng Clinical Medical School of Inner Mongolia Medical University, Chifeng, 024000, PR ChinaState Key Laboratory of Pathogenesis, Prevention and Treatment of High Incidence Diseases in Central Asia, First Affiliated Hospital of Xinjiang Medical University, Urumqi, 830000, PR ChinaHepatology Department, Ningbo Hwamei Hospital, University of Chinese Academy of Sciences, Ningbo, 315010, PR ChinaDepartment of Clinical Laboratory, The Second Hospital, Cheeloo College of Medicine, Shandong University, 247 Beiyuan Street, Jinan 250033, Shandong, PR China; Shandong Provincial Clinical Medicine Research Center for Clinical Laboratory, Jinan, 250033, PR China; Corresponding author. Department of Clinical Laboratory, The Second Hospital, Cheeloo College of Medicine, Shandong University, 247 Beiyuan Street, Jinan, 250033, Shandong, PR China.Berry Oncology Corporation, Beijing, 100102, PR China; Corresponding author. Berry Oncology Corporation, Beijing, 100102, PR China.Department of Infectious Diseases, State Key Laboratory of Organ Failure Research, Guangdong Provincial Key Laboratory of Viral Hepatitis Research, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, PR China; Hepatology Unit, Shenzhen Hospital, Southern Medical University, Shenzhen, PR China; Corresponding author. State Key Laboratory of Organ Failure Research, Guangdong Provincial Key Laboratory of Viral Hepatitis Research, Department of Infectious Diseases and Hepatology Unit, Nanfang Hospital, Southern Medical University, Guangzhou, 510445, PR China.National Center of Liver Cancer, Navel Medical University, Shanghai, 210822, PR China; International Cooperation Laboratory on Signal Transduction, Eastern Hepatobiliary Surgery Institute/Hospital, Shanghai, 200438, PR China; Key Laboratory of Signaling Regulation and Targeting Therapy of Liver Cancer (SMMU), Ministry of Education, Shanghai, 200438, PR China; Shanghai Key Laboratory of Hepatobiliary Tumor Biology (EHBH), Shanghai, 200438, PR China; Corresponding author. International Co-operation Laboratory on Signal Transduction, Eastern Hepatobiliary Surgery Institute/Hospital, Shanghai, 200438, PR China.Summary: Background: Liver cirrhosis (LC) is the highest risk factor for hepatocellular carcinoma (HCC) development worldwide. The efficacy of the guideline-recommended surveillance methods for patients with LC remains unpromising. Methods: A total of 4367 LCs not previously known to have HCC and 510 HCCs from 16 hospitals across 11 provinces of China were recruited in this multi-center, large-scale, cross-sectional study. Participants were divided into Stage Ⅰ cohort (510 HCCs and 2074 LCs) and Stage Ⅱ cohort (2293 LCs) according to their enrollment time and underwent Tri-phasic CT/enhanced MRI, US, AFP, and cell-free DNA (cfDNA). A screening model called PreCar Score was established based on five features of cfDNA using Stage Ⅰ cohort. Surveillance performance of PreCar Score alone or in combination with US/AFP was evaluated in Stage Ⅱ cohort. Findings: PreCar Score showed a significantly higher sensitivity for the detection of early/very early HCC (Barcelona stage A/0) in contrast to US (sensitivity of 51.32% [95% CI: 39.66%–62.84%] at 95.53% [95% CI: 94.62%–96.38%] specificity for PreCar Score; sensitivity of 23.68% [95% CI: 14.99%–35.07%] at 99.37% [95% CI: 98.91%–99.64%] specificity for US) (P < 0.01, Fisher's exact test). PreCar Score plus US further achieved a higher sensitivity of 60.53% at 95.08% specificity for early/very early HCC screening. Interpretation: Our study developed and validated a cfDNA-based screening tool (PreCar Score) for HCC in cohorts at high risk. The combination of PreCar Score and US can serve as a promising and practical strategy for routine HCC care. Funding: A full list of funding bodies that contributed to this study can be found in Acknowledgments section.http://www.sciencedirect.com/science/article/pii/S2352396423005285Early hepatocellular carcinomaSurveillanceCell-free DNALiquid biopsy |
| spellingShingle | Lei Chen Tong Wu Rong Fan Yun-Song Qian Jing-Feng Liu Jian Bai Bo Zheng Xiao-Long Liu Dan Zheng Lu-Tao Du Guo-Qing Jiang Ying-Chao Wang Xiao-Tang Fan Guo-Hong Deng Chun-Ying Wang Feng Shen He-Ping Hu Qing-Zheng Zhang Yi-Nong Ye Jing Zhang Yan-Hang Gao Jie Xia Hua-Dong Yan Min-Feng Liang Yan-Long Yu Fu-Ming Sun Yu-Jing Gao Jian Sun Chun-Xiu Zhong Yin Wang Hui Wang Fei Kong Jin-Ming Chen Hao Wen Bo-Ming Wu Chuan-Xin Wang Lin Wu Jin-Lin Hou Hong-Yang Wang Cell-free DNA testing for early hepatocellular carcinoma surveillanceResearch in context EBioMedicine Early hepatocellular carcinoma Surveillance Cell-free DNA Liquid biopsy |
| title | Cell-free DNA testing for early hepatocellular carcinoma surveillanceResearch in context |
| title_full | Cell-free DNA testing for early hepatocellular carcinoma surveillanceResearch in context |
| title_fullStr | Cell-free DNA testing for early hepatocellular carcinoma surveillanceResearch in context |
| title_full_unstemmed | Cell-free DNA testing for early hepatocellular carcinoma surveillanceResearch in context |
| title_short | Cell-free DNA testing for early hepatocellular carcinoma surveillanceResearch in context |
| title_sort | cell free dna testing for early hepatocellular carcinoma surveillanceresearch in context |
| topic | Early hepatocellular carcinoma Surveillance Cell-free DNA Liquid biopsy |
| url | http://www.sciencedirect.com/science/article/pii/S2352396423005285 |
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