EBioMedicine (Feb 2024)
Cell-free DNA testing for early hepatocellular carcinoma surveillanceResearch in context
- 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
Affiliations
- Lei Chen
- 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; Corresponding author. International Co-operation Laboratory on Signal Transduction, Eastern Hepatobiliary Surgery Institute/Hospital, Shanghai, 200438, PR China.
- Tong Wu
- 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 China
- Rong Fan
- 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
- Yun-Song Qian
- Hepatology Department, Ningbo Hwamei Hospital, University of Chinese Academy of Sciences, Ningbo, 315010, PR China
- Jing-Feng Liu
- The United Innovation of Mengchao Hepatobiliary Technology Key Laboratory of Fujian Province, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou, 350025, PR China
- Jian Bai
- Berry Oncology Corporation, Beijing, 100102, PR China
- Bo Zheng
- 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
- Xiao-Long Liu
- The United Innovation of Mengchao Hepatobiliary Technology Key Laboratory of Fujian Province, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou, 350025, PR China
- Dan Zheng
- Department of Gastroenterology, The Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430014, PR China
- Lu-Tao Du
- Department 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
- Guo-Qing Jiang
- Department of Hepatobiliary Surgery, Clinical Medical College, Yangzhou University, Yangzhou, 225001, PR China
- Ying-Chao Wang
- The United Innovation of Mengchao Hepatobiliary Technology Key Laboratory of Fujian Province, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou, 350025, PR China
- Xiao-Tang Fan
- Department of Hepatology, First Affiliated Hospital of Xinjiang Medical University, Urumqi, 830000, PR China
- Guo-Hong Deng
- Department of Infectious Diseases, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing, 400038, PR China
- Chun-Ying Wang
- Xuzhou Infectious Diseases Hospital, Xuzhou, 221004, PR China
- Feng Shen
- Department of Hepatic Surgery IV, Eastern Hepatobiliary Surgery Institute, Second Military Medical University, Shanghai, 200438, PR China
- He-Ping Hu
- Department of Hepatobiliary Medicine, Shanghai Eastern Hepatobiliary Surgery Hospital, Shanghai, 210822, PR China
- Qing-Zheng Zhang
- Berry Oncology Corporation, Beijing, 100102, PR China
- Yi-Nong Ye
- The Department of Infectious Disease, The First People's Hospital of Foshan, Foshan City, 528000, PR China
- Jing Zhang
- Berry Oncology Corporation, Beijing, 100102, PR China
- Yan-Hang Gao
- The First Hospital of Jilin University, Jilin, 130021, PR China
- Jie Xia
- Department of Infectious Diseases, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing, 400038, PR China
- Hua-Dong Yan
- Hepatology Department, Ningbo Hwamei Hospital, University of Chinese Academy of Sciences, Ningbo, 315010, PR China
- Min-Feng Liang
- The Department of Infectious Disease, The First People's Hospital of Foshan, Foshan City, 528000, PR China
- Yan-Long Yu
- Chifeng Clinical Medical School of Inner Mongolia Medical University, Chifeng, 024000, PR China
- Fu-Ming Sun
- Berry Oncology Corporation, Beijing, 100102, PR China
- Yu-Jing Gao
- Xuzhou Infectious Diseases Hospital, Xuzhou, 221004, PR China
- Jian Sun
- 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
- Chun-Xiu Zhong
- 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
- Yin Wang
- Berry Oncology Corporation, Beijing, 100102, PR China
- Hui Wang
- Department of Hepatobiliary Medicine, Shanghai Eastern Hepatobiliary Surgery Hospital, Shanghai, 210822, PR China
- Fei Kong
- The First Hospital of Jilin University, Jilin, 130021, PR China
- Jin-Ming Chen
- Chifeng Clinical Medical School of Inner Mongolia Medical University, Chifeng, 024000, PR China
- Hao Wen
- State Key Laboratory of Pathogenesis, Prevention and Treatment of High Incidence Diseases in Central Asia, First Affiliated Hospital of Xinjiang Medical University, Urumqi, 830000, PR China
- Bo-Ming Wu
- Hepatology Department, Ningbo Hwamei Hospital, University of Chinese Academy of Sciences, Ningbo, 315010, PR China
- Chuan-Xin Wang
- Department 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.
- Lin Wu
- Berry Oncology Corporation, Beijing, 100102, PR China; Corresponding author. Berry Oncology Corporation, Beijing, 100102, PR China.
- Jin-Lin Hou
- 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.
- Hong-Yang Wang
- 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.
- Journal volume & issue
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Vol. 100
p. 104962
Abstract
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.
