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Liquid biopsy using cell-free DNA in the early diagnosis of hepatocellular carcinoma

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Abstract

Hepatocellular carcinoma ranks fourth in cancer-related causes of death worldwide and second in China. Patients with hepatocellular carcinoma (HCC) at the early stage have a better prognosis compared to HCC patients at the late stage. Therefore, early screening for HCC is critical for clinical treatment decisions and improving the prognosis of patients. Ultrasound (US), computed tomography (CT), and serum alpha fetoprotein (AFP) have been used to screen HCC, but HCC is still difficult to be diagnosed in the early stage due to the low sensitivity of the above methods. It is urgent to find a method with high sensitivity and specificity for the early diagnosis of HCC. Liquid biopsy is a noninvasive detection method using blood or other bodily fluids. Cell-free DNA (cfDNA) and circulating tumor DNA (ctDNA) are important biomarkers for liquid biopsy. Recently, HCC screening methods using the application of cfDNA and ctDNA have become the hot spot of early HCC diagnostics. In this mini review, we summarize the latest research progress of liquid biopsy based on blood cfDNA in early screening of HCC.

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Data availability

The datasets generated during and/or analysed during the current study are available from the corresponding author on reasonable request.

References

  1. Villanueva A, Hepatocellular Carcinoma N, Engl JM (2019) 380 (15),1450–1462. https://doi.org/10.1056/NEJMra1713263

  2. Heimbach JK, Kulik LM, Finn RS, Sirlin CB, Abecassis MM, Roberts LR, Zhu AX, Murad MH, Marrero J (2018) A. AASLD Guidelines for the treatment of Hepatocellular Carcinoma: Heimbach et Al. Hepatology 67(1):358–380. https://doi.org/10.1002/hep.29086

    Article  PubMed  Google Scholar 

  3. El-Serag HB (2012) Epidemiology of viral Hepatitis and Hepatocellular Carcinoma. Gastroenterology 142(6):1264–1273. e1

    Article  PubMed  Google Scholar 

  4. Yang JD, Roberts LR, Hepatocellular Carcinoma (2010) A Global View. Nat Rev Gastroenterol Hepatol 7(8):448–458. https://doi.org/10.1038/nrgastro.2010.100

    Article  PubMed  PubMed Central  Google Scholar 

  5. Yang JD, Hainaut P, Gores GJ, Amadou A, Plymoth A, Roberts LR (2019) A Global View of Hepatocellular Carcinoma: Trends, Risk, Prevention and Management. Nat Rev Gastroenterol Hepatol 16(10):589–604. https://doi.org/10.1038/s41575-019-0186-y

    Article  PubMed  PubMed Central  Google Scholar 

  6. Lampertico P, Agarwal K, Berg T, Buti M, Janssen HLA, Papatheodoridis G, Zoulim F, Tacke F EASL 2017 clinical practice guidelines on the management of Hepatitis B Virus infection. Journal of Hepatology 2017, 67 (2),370–398. https://doi.org/10.1016/j.jhep.2017.03.021

  7. Wu X, Li J, Gassa A, Buchner D, Alakus H, Dong Q, Ren N, Liu M, Odenthal M, Stippel D, Bruns C, Zhao Y, Wahba R (2020) Circulating tumor DNA as an emerging Liquid Biopsy Biomarker for early diagnosis and therapeutic monitoring in Hepatocellular Carcinoma. Int J Biol Sci 16(9):1551–1562. https://doi.org/10.7150/ijbs.44024

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Lang H, Sotiropoulos GC, Brokalaki EI, Schmitz KJ, Bertona C, Meyer G, Frilling A, Paul A, Malagó M, Broelsch CE (2007) Survival and recurrence rates after resection for Hepatocellular Carcinoma in noncirrhotic livers. J Am Coll Surg 205(1):27–36. https://doi.org/10.1016/j.jamcollsurg.2007.03.002

    Article  PubMed  Google Scholar 

  9. NCCN Guidelines for Hepatobiliary Cancers.

  10. Tzartzeva K Surveillance imaging and alpha fetoprotein for early detection of Hepatocellular Carcinoma in patients with cirrhosis: a Meta-analysis. 34. https://doi.org/10.1053/j.gastro.2018.01.064

  11. Zhang X, Wang Z, Tang W, Wang X, Liu R, Bao H, Chen X, Wei Y, Wu S, Bao H, Wu X, Shao Y, Fan J, Zhou J (2022) Ultrasensitive and affordable assay for early detection of primary Liver Cancer using plasma cell-free DNA fragmentomics. Hepatology 76(2):317–329. https://doi.org/10.1002/hep.32308

    Article  CAS  PubMed  Google Scholar 

  12. Guo J, Seo Y, Ren S, Hong S, Lee D, Kim S, Jiang Y (2016) Diagnostic performance of contrast-enhanced Multidetector Computed Tomography and Gadoxetic Acid Disodium-Enhanced magnetic resonance imaging in detecting Hepatocellular Carcinoma: direct comparison and a Meta-analysis. Abdom Radiol 41(10):1960–1972. https://doi.org/10.1007/s00261-016-0807-7

    Article  Google Scholar 

  13. The PreCar Team, Chen L, Abou-Alfa GK, Zheng B, Liu J-F, Bai J, Du L-T, Qian Y-S, Fan R, Liu X-L, Wu L, Hou J-L, Wang H-Y (2021) Genome-scale profiling of circulating cell-free DNA signatures for early detection of Hepatocellular Carcinoma in Cirrhotic Patients. Cell Res 31(5):589–592. https://doi.org/10.1038/s41422-020-00457-7

    Article  CAS  Google Scholar 

  14. Harris PS, Hansen RM, Gray ME, Massoud OI, McGuire BM, Shoreibah MG (2019) Hepatocellular Carcinoma Surveillance: an evidence-based Approach. WJG 25(13):1550–1559. https://doi.org/10.3748/wjg.v25.i13.1550

    Article  PubMed  PubMed Central  Google Scholar 

  15. Crowley E, Di Nicolantonio F, Loupakis F, Bardelli A (2013) Liquid Biopsy: Monitoring Cancer-Genetics in the blood. Nat Rev Clin Oncol 10(8):472–484. https://doi.org/10.1038/nrclinonc.2013.110

    Article  CAS  PubMed  Google Scholar 

  16. Issa IA, Noureddine M (2017) Colorectal Cancer Screening: An Updated Review of the Available Options. WJG 23 (28), 5086. https://doi.org/10.3748/wjg.v23.i28.5086

  17. Hench IB, Hench J, Tolnay M (2018) Liquid biopsy in clinical management of breast, lung, and Colorectal Cancer. Front Med 5:9. https://doi.org/10.3389/fmed.2018.00009

    Article  Google Scholar 

  18. Morrison GJ, Goldkorn A (2018) Development and application of Liquid Biopsies in metastatic prostate Cancer. Curr Oncol Rep 20(4):35. https://doi.org/10.1007/s11912-018-0683-0

    Article  PubMed  PubMed Central  Google Scholar 

  19. Chung JH, Pavlick D, Hartmaier R, Schrock AB, Young L, Forcier B, Ye P, Levin MK, Goldberg M, Burris H, Gay LM, Hoffman AD, Stephens PJ, Frampton GM, Lipson DM, Nguyen DM, Ganesan S, Park BH, Vahdat LT, Leyland-Jones B, Mughal TI, Pusztai L, O’Shaughnessy J, Miller VA, Ross JS, Ali SM (2017) Hybrid capture-based genomic profiling of circulating Tumor DNA from patients with estrogen receptor-positive metastatic breast Cancer. Ann Oncol 28(11):2866–2873. https://doi.org/10.1093/annonc/mdx490

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Pan Y, Ji JS, Jin JG, Kuo WP, Kang H (2017) Cancer Liquid Biopsy: is it ready for clinic? IEEE Pulse 8(1):23–27. https://doi.org/10.1109/MPUL.2016.2630838

    Article  PubMed  Google Scholar 

  21. Moss J, Magenheim J, Neiman D, Zemmour H, Loyfer N, Korach A, Samet Y, Maoz M, Druid H, Arner P, Fu K-Y, Kiss E, Spalding KL, Landesberg G, Zick A, Grinshpun A, Shapiro AMJ, Grompe M, Wittenberg AD, Glaser B, Shemer R, Kaplan T, Dor Y (2018) Comprehensive Human cell-type methylation Atlas reveals Origins of circulating cell-free DNA in Health and Disease. Nat Commun 9(1):5068. https://doi.org/10.1038/s41467-018-07466-6

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Lyu X, Tsui Y-M, Ho DW-H, Ng IO-L (2022) Liquid Biopsy using cell-free or circulating tumor DNA in the management of Hepatocellular Carcinoma. Cell Mol Gastroenterol Hepatol 13(6):1611–1624. https://doi.org/10.1016/j.jcmgh.2022.02.008

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Howell J, Atkinson SR, Pinato DJ, Knapp S, Ward C, Minisini R, Burlone ME, Leutner M, Pirisi M, Büttner R, Khan SA, Thursz M, Odenthal M, Sharma R (2019) Identification of mutations in circulating cell-free Tumour DNA as a Biomarker in Hepatocellular Carcinoma. Eur J Cancer 116:56–66. https://doi.org/10.1016/j.ejca.2019.04.014

    Article  CAS  PubMed  Google Scholar 

  24. Yan L, Chen Y, Zhou J, Zhao H, Zhang H, Wang G Diagnostic value of circulating cell-free DNA levels for Hepatocellular Carcinoma. International Journal of Infectious Diseases 2018, 67,92–97. https://doi.org/10.1016/j.ijid.2017.12.002

  25. Xu H, Zhu X, Xu Z, Hu Y, Bo S, Xing T, Zhu K (2015) Non-invasive analysis of genomic Copy Number Variation in patients with Hepatocellular Carcinoma by Next Generation DNA sequencing. J Cancer 6(3):247–253. https://doi.org/10.7150/jca.10747

    Article  PubMed  PubMed Central  Google Scholar 

  26. Tao K, Bian Z, Zhang Q, Guo X, Yin C, Wang Y, Zhou K, Wan S, Shi M, Bao D, Yang C, Xing J (2020) Machine learning-based genome-wide interrogation of somatic Copy Number Aberrations in circulating Tumor DNA for early detection of Hepatocellular Carcinoma. EBioMedicine 56:102811. https://doi.org/10.1016/j.ebiom.2020.102811

    Article  PubMed  PubMed Central  Google Scholar 

  27. Guichard C, Amaddeo G, Imbeaud S, Ladeiro Y, Pelletier L, Maad IB, Calderaro J, Bioulac-Sage P, Letexier M, Degos F, Clément B, Balabaud C, Chevet E, Laurent A, Couchy G, Letouzé E, Calvo F, Zucman-Rossi J (2012) Integrated Analysis of somatic mutations and Focal Copy-Number changes identifies key genes and pathways in Hepatocellular Carcinoma. Nat Genet 44(6):694–698. https://doi.org/10.1038/ng.2256

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Kaseb AO, Sánchez NS, Sen S, Kelley RK, Tan B, Bocobo AG, Lim KH, Abdel-Wahab R, Uemura M, Pestana RC, Qiao W, Xiao L, Morris J, Amin HM, Hassan MM, Rashid A, Banks KC, Lanman RB, Talasaz A, Mills-Shaw KR, George B, Haque A, Raghav KPS, Wolff RA, Yao JC, Meric-Bernstam F, Ikeda S, Kurzrock R (2019) Molecular profiling of Hepatocellular Carcinoma using circulating cell-free DNA. Clin Cancer Res 25(20):6107–6118. https://doi.org/10.1158/1078-0432.CCR-18-3341

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Totoki Y, Tatsuno K, Covington KR, Ueda H, Creighton CJ, Kato M, Tsuji S, Donehower LA, Slagle BL, Nakamura H, Yamamoto S, Shinbrot E, Hama N, Lehmkuhl M, Hosoda F, Arai Y, Walker K, Dahdouli M, Gotoh K, Nagae G, Gingras M-C, Muzny DM, Ojima H, Shimada K, Midorikawa Y, Goss JA, Cotton R, Hayashi A, Shibahara J, Ishikawa S, Guiteau J, Tanaka M, Urushidate T, Ohashi S, Okada N, Doddapaneni H, Wang M, Zhu Y, Dinh H, Okusaka T, Kokudo N, Kosuge T, Takayama T, Fukayama M, Gibbs RA, Wheeler DA, Aburatani H (2014) Shibata, T. Trans-Ancestry Mutational Landscape of Hepatocellular Carcinoma Genomes. Nat Genet 46(12):1267–1273. https://doi.org/10.1038/ng.3126

    Article  CAS  PubMed  Google Scholar 

  30. Qu C, Wang Y, Wang P, Chen K, Wang M, Zeng H, Lu J, Song Q, Diplas BH, Tan D, Fan C, Guo Q, Zhu Z, Yin H, Jiang L, Chen X, Zhao H, He H, Wang Y, Li G, Bi X, Zhao X, Chen T, Tang H, Lv C, Wang D, Chen W, Zhou J, Zhao H, Cai J, Wang X, Wang S, Yan H, Zeng Y-X, Cavenee WK, Jiao Y (2019) Detection of Early-Stage Hepatocellular Carcinoma in Asymptomatic HBsAg-Seropositive Individuals by Liquid Biopsy. Proc. Natl. Acad. Sci. U.S.A. 116 (13), 6308–6312. https://doi.org/10.1073/pnas.1819799116

  31. Huang A, Zhang X, Zhou S-L, Cao Y, Huang X-W, Fan J, Yang X-R, Zhou J (2016) Plasma circulating Cell-Free DNA Integrity as a Promising Biomarker for diagnosis and surveillance in patients with Hepatocellular Carcinoma. J Cancer 7(13):1798–1803. https://doi.org/10.7150/jca.15618

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Jiang P, Chan CWM, Chan KCA, Cheng SH, Wong J, Wong VW-S, Wong GLH, Chan SL, Mok TSK, Chan HLY, Lai PBS, Chiu RWK, Lo YMD (2015) Lengthening and Shortening of Plasma DNA in Hepatocellular Carcinoma Patients. Proc. Natl. Acad. Sci. U.S.A. 112 (11). https://doi.org/10.1073/pnas.1500076112

  33. Meng Z, Ren Q, Zhong G, Li S, Chen Y, Wu W, Feng Y, Mao M, Zhang F, Long G (2021) Noninvasive detection of Hepatocellular Carcinoma with circulating Tumor DNA features and α-Fetoprotein. J Mol Diagn 23(9):1174–1184. https://doi.org/10.1016/j.jmoldx.2021.06.003

    Article  CAS  PubMed  Google Scholar 

  34. Jiang P, Sun K, Tong YK, Cheng SH, Cheng THT, Heung MMS, Wong J, Wong VWS, Chan HLY, Chan KCA, Lo YMD, Chiu RWK (2018) Preferred End Coordinates and Somatic Variants as Signatures of Circulating Tumor DNA Associated with Hepatocellular Carcinoma. Proc. Natl. Acad. Sci. U.S.A. 115 (46). https://doi.org/10.1073/pnas.1814616115

  35. Jiang P, Sun K, Peng W, Cheng SH, Ni M, Yeung PC, Heung MMS, Xie T, Shang H, Zhou Z, Chan RWY, Wong J, Wong VWS, Poon LC, Leung TY, Lam WKJ, Chan JYK, Chan HLY, Chan KCA, Chiu RWK, Lo YM (2020) D. plasma DNA end-motif profiling as a fragmentomic marker in Cancer, pregnancy, and transplantation. Cancer Discov 10(5):664–673. https://doi.org/10.1158/2159-8290.CD-19-0622

    Article  CAS  PubMed  Google Scholar 

  36. Manel E Epigenetics in Cancer. N engl j med 2008, 12. https://doi.org/10.1056/NEJMra072067

  37. Chatterjee R, Vinson C, CpG Methylation Recruits Sequence Specific Transcription Factors Essential for Tissue Specific Gene Expression (2012) Biochimica et Biophysica Acta (BBA) - Gene Regulatory Mechanisms. 1819(7):763–770. https://doi.org/10.1016/j.bbagrm.2012.02.014

  38. Kisiel JB, Dukek BA, Kanipakam VSR, Ghoz R, Yab HM, Berger TC, Taylor CK, Foote WR, Giama PH, Onyirioha NH, Abdallah K, Burger MA, Slettedahl KN, Mahoney SW, Smyrk DW, Lewis TC, Giakoumopoulos JT, Allawi M, Lidgard HT, Roberts GP, Ahlquist LR (2019) D. A. Hepatocellular Carcinoma Detection by Plasma Methylated DNA: Discovery, Phase I Pilot, and Phase II Clinical Validation. Hepatology hep.30244. https://doi.org/10.1002/hep.30244

  39. Xu R, Wei W, Krawczyk M, Wang W, Luo H, Flagg K, Yi S, Shi W, Quan Q, Li K, Zheng L, Zhang H, Caughey BA, Zhao Q, Hou J, Zhang R, Xu Y, Cai H, Li G, Hou R, Zhong Z, Lin D, Fu X, Zhu J, Duan Y, Yu M, Ying B, Zhang W, Wang J, Zhang E, Zhang C, Li O, Guo R, Carter H, Zhu J, Hao X, Zhang K (2017) Circulating Tumour DNA methylation markers for diagnosis and prognosis of Hepatocellular Carcinoma. Nat Mater 16(11):1155–1161. https://doi.org/10.1038/nmat4997

    Article  CAS  PubMed  Google Scholar 

  40. Luo B, Ma F, Liu H, Hu J, Rao L, Liu C, Jiang Y, Kuangzeng S, Lin X, Wang C, Lei Y, Si Z, Chen G, Zhou N, Liang C, Jiang F, Liu F, Dai W, Liu W, Gao Y, Li Z, Li X, Zhou G, Li B, Zhang Z, Nian W, Luo L, Liu X (2022) Cell-free DNA methylation markers for Differential diagnosis of Hepatocellular Carcinoma. BMC Med 20(1):8. https://doi.org/10.1186/s12916-021-02201-3

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Chalasani NP, Ramasubramanian TS, Bhattacharya A, Olson MC, Edwards V, Roberts DK, Kisiel LR, Reddy JB, Lidgard KR, Johnson GP, Bruinsma SC (2021) A novel blood-based panel of methylated DNA and protein markers for detection of early-stage Hepatocellular Carcinoma. Clin Gastroenterol Hepatol 19(12):2597–2605e4. https://doi.org/10.1016/j.cgh.2020.08.065

    Article  CAS  PubMed  Google Scholar 

  42. Chalasani NP, Porter K, Bhattacharya A, Book AJ, Neis BM, Xiong KM, Ramasubramanian TS, Edwards DK, Chen I, Johnson S, Roberts LR, Kisiel JB, Reddy KR, Singal AG, Olson MC, Bruinsma JJ (2022) Validation of a Novel Multitarget Blood Test shows high sensitivity to Detect Early Stage Hepatocellular Carcinoma. Clin Gastroenterol Hepatol 20(1):173–182e7. https://doi.org/10.1016/j.cgh.2021.08.010

    Article  CAS  PubMed  Google Scholar 

  43. Klug M, Schmidhofer S, Gebhard C, Andreesen R, Rehli M (2013) 5-Hydroxymethylcytosine is an essential Intermediate of active DNA demethylation processes in primary human monocytes. 8. https://doi.org/10.1186/gb-2013-14-5-r46

  44. Cai J, Chen L, Zhang Z, Zhang X, Lu X, Liu W, Shi G, Ge Y, Gao P, Yang Y, Ke A, Xiao L, Dong R, Zhu Y, Yang X, Wang J, Zhu T, Yang D, Huang X, Sui C, Qiu S, Shen F, Sun H, Zhou W, Zhou J, Nie J, Zeng C, Stroup EK, Zhang X, Chiu BC-H, Lau WY, He C, Wang H, Zhang W, Fan J (2019) Genome-wide mapping of 5-Hydroxymethylcytosines in circulating cell-free DNA as a Non-Invasive Approach for early detection of Hepatocellular Carcinoma. Gut 68(12):2195–2205. https://doi.org/10.1136/gutjnl-2019-318882

    Article  CAS  PubMed  Google Scholar 

  45. Ye W, Siwko S, Tsai RYL (2021) Sex and race-related DNA methylation changes in Hepatocellular Carcinoma. IJMS 22(8):3820. https://doi.org/10.3390/ijms22083820

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. Lin N, Lin Y, Xu J, Liu D, Li D, Meng H, Gallant MA, Kubota N, Roy D, Li JS, Gorospe EC, Sherman M, Gish RG, Abou-Alfa GK, Nguyen MH, Taggart DJ, Van Etten RA, Hoshida Y, Li W (2022) A Multi‐analyte cell‐free DNA –Based blood test for early detection of Hepatocellular Carcinoma. Hepatol Commun 6(7):1753–1763. https://doi.org/10.1002/hep4.1918

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. Yang X, Zhou J, Fan J et al (2022) Early detection of hepatocellular carcinoma with methylation and fragmentation signatures of circulating tumour DNA: a prospective, multicentre, case-control, observational study. Lancet Oncol 23:S15. https://doi.org/10.1016/S1470-2045(22)00414-4

    Article  Google Scholar 

  48. Lewin J, Kottwitz D, Aoyama J et al (2021) Plasma cell free DNA methylation markers for hepatocellular carcinoma surveillance in patients with cirrhosis: a case control study. BMC Gastroenterol 21(1):136. https://doi.org/10.1186/s12876-021-01714-8

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  49. Kotoh Y, Suehiro Y, Saeki I et al (2020) Novel Liquid Biopsy Test based on a sensitive methylated SEPT9 assay for diagnosing Hepatocellular Carcinoma. Hepatol Commun 0(0):10. https://doi.org/10.1002/hep4.1469

    Article  CAS  Google Scholar 

  50. Oussalah A, Rischer S, Bensenane M et al (2018) Plasma mSEPT9: a novel circulating cell-free DNA-Based epigenetic biomarker to diagnose Hepatocellular Carcinoma. EBioMedicine 30:138–147. https://doi.org/10.1016/j.ebiom.2018.03.029

    Article  PubMed  PubMed Central  Google Scholar 

  51. Qi T, Pan M, Shi H, Wang L, Bai Y, Ge Q, Cell-Free DNA (2023) Fragmentomics: The Novel Promising Biomarker. IJMS. ;24(2):1503. doi:https://doi.org/10.3390/ijms24021503

  52. van der Pol Y, Moldovan N, Verkuijlen S et al (2022) The Effect of Preanalytical and physiological variables on cell-free DNA fragmentation. Clin Chem 68(6):803–813. https://doi.org/10.1093/clinchem/hvac029

    Article  PubMed  Google Scholar 

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Authors and Affiliations

  1. The oncology department, Xiangtan Central Hospital, Hunan, China

    Shiqi Hu

  2. The Medical Department, The State Key Lab of Translational Medicine and Innovative Drug Development, Jiangsu Simcere Diagnostics Co., Ltd, Nanjing Simcere Medical Laboratory Science Co., Ltd, Nanjing, 210002, China

    Yaqin Liu, Qidong Yang, Lin Chen, Huizi Chai, Mingzhe Xiao & Chuang Qi

  3. Department of Hepatobiliary and Pancreatic Surgery, General Surgery Center, The First Hospital of Jilin University, 71 Xinmin Street, Chaoyang District, Changchun, 130000, Jilin, China

    Wei Qiu

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Contributions

Shiqi Hu: Investigation, Data Curation, Formal analysis, Writing - Original Draft；Yaqin Liu: Investigation, Data Curation, Writing - Original Draft；Qidong Yang: Investigation, Data Curation, Writing - Original Draft；Lin Chen: Data Curation；Huizi Chai: Data Curation；Mingzhe Xiao: Formal analysis, Writing - Review & Editing；Chuang Qi: Formal analysis, Writing - Review & Editing；Wei Qiu [Corresponding author]: Conceptualization, Methodology, Writing - Review & Editing；.

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Hu, S., Liu, Y., Yang, Q. et al. Liquid biopsy using cell-free DNA in the early diagnosis of hepatocellular carcinoma. Invest New Drugs 41, 532–538 (2023). https://doi.org/10.1007/s10637-023-01363-6

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