Volume 31, No 5, May 2021

ISSN: 1001-0602 
EISSN: 1748-7838 2018 
impact factor 17.848* 
(Clarivate Analytics, 2019)

Volume 31 Issue 5, May 2021: 589-592   |  Open Access

LETTERS TO THE EDITOR

Genome-scale profiling of circulating cell-free DNA signatures for early detection of hepatocellular carcinoma in cirrhotic patients

Lei Chen^1,2 , Ghassan K. Abou-Alfa^3,4 , Bo Zheng^1,2 , Jing-Feng Liu⁵ , Jian Bai⁶ , Lu-Tao Du^7,8 , Yun-Song Qian⁹ , Rong Fan¹⁰ , Xiao-Long Liu⁵ , Lin Wu^6,* , Jin-Lin Hou^10,* , Hong-Yang Wang^1,2,11,12,* , The PreCar Team¹³

¹National Center for Liver Cancer, Shanghai 210822, China
²International Cooperation Laboratory on Signal Transduction, Eastern Hepatobiliary Surgery Institute, Second Military Medical University, Shanghai 200438, China
³Memorial Sloan Kettering Cancer Center, New York, NY, USA
⁴Weill Medical College at Cornell University, New York, NY, USA
⁵The United Innovation of Mengchao Hepatobiliary Technology Key Laboratory of Fujian Province, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou, Fujian 350025, China
⁶Berry Oncology Corporation, Beijing 100102, China
⁷Department of Clinical Laboratory, The Second Hospital of Shandong University, 247 Beiyuan Street, Jinan, Shandong 250033, China
⁸The Clinical Research Center of Shandong Province for Clinical Laboratory, 247 Beiyuan Street, Jinan, Shandong 250033, China
⁹Hepatology Department, Ningbo Hwamei Hospital, University of Chinese Academy of Sciences, Ningbo, Zhejiang 315010, China
¹⁰Department of Infectious Diseases, State Key Laboratory of Organ Failure Research, Guangdong Provincial Key Laboratory of Viral Hepatitis Research, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong 510515, China
¹¹Key Laboratory of Signaling Regulation and Targeting Therapy of Liver Cancer (SMMU), Ministry of Education, Shanghai 200438, China
¹²Shanghai Key Laboratory of Hepatobiliary Tumor Biology (EHBH), Shanghai 200438, China
¹³A list of the PreCar Team members and their affiliations appears at the end of the paper.
These authors contributed equally: Lei Chen, Ghassan K. Abou-Alfa, Bo Zheng, Jing-Feng Liu, Jian Bai, Lu-Tao Du, Yun-Song Qian, Rong Fan, Xiao-Long Liu Correspondence: Lin Wu(wulin@berryoncology.com)Jin-Lin Hou(jlhousmu@163.com)Hong-Yang Wang(hywangk@vip.sina.com)

Dear Editor,

Hepatocellular carcinoma (HCC) is the second most deadly cancer worldwide.1 Cirrhosis of different causes predisposes patients to HCC, increasing the annual HCC incidence by 2%–4%.1 The development of cirrhosis facilitates a series of genetic or epigenetic changes, resulting in the formation of dysplastic nodules, a premalignant stage in HCC.1 HCC diagnosis at an early stage contributes to an improved prognosis with the possibility of curative treatment. Due to the low accuracy of current diagnostic methods, it is urgently needed to explore new non-invasive strategies for early HCC diagnosis in cirrhotic patients. Hence, we collected cell-free DNA (cfDNA) samples from a total of 2250 patients with liver cirrhosis (LC), 508 with HCC, and 476 healthy controls (CTRL), from 13 hospitals in 11 provinces of China, and randomly assigned them to training, validation and test cohorts for development and evaluation of diagnostic model. We employed a state-of-the-art next-generation sequencing (NGS) technology to acquire genome-wide 5-hydroxymethylcytosine (5-hmc),2 nucleosome footprint (NF),3 5′ end motif4 and fragmentation5,6,7 profiles of cfDNAs from all enrolled patients. Using a logistic regression method, we constructed a weighted diagnostic model based on the performance of these four features.

https://doi.org/10.1038/s41422-020-00457-7

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