Research progress on application of circulating free DNA in diagnosis and treatment of hepatocellular carcinoma_CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Authors：

ZHOU Kai ,  CHEN Gang , SONG Shuxian , PA Chengzhou

Department of Hepatobiliary Surgery, The First People’s Hospital of Kunming/The Affiliated Ganmei Hospital of Kunming Medical University, Kunming 650100, P. R. China;

Corresponding author：

CHEN Gang, Email: kmcg123@163.com

Keywords：

circulating free DNA; hepatocellular carcinoma; precision medicine; disease management

DOI：

10.7507/1007-9424.202408109

Video：

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Abstract Full text Figures/Tables Video References Cited by

Objective To summarize the application of circulating free DNA (cfDNA) in the diagnosis and treatment of hepatocellular carcinoma (HCC). Method The relevant literature on the application of cfDNA in the diagnosis and treatment of HCC from both domestic and international sources were reviewed and summarized. Results cfDNA is an emerging biomarker in recent years. At present, a large number of studies had used different detection methods to detect abnormal methylation, hot spot mutation, gene copy number variation, and quantitative detection of cfDNA concentration. It was found that cfDNA could be used in the management process of early diagnosis, treatment guidance, and efficacy evaluation of HCC patients. Conclusions cfDNA detection is a good tool in the diagnosis and treatment of HCC, which can help clinicians make-decisions and bring more possibilities for the diagnosis and treatment of HCC, which is of great significance for changing the current diagnosis and treatment of HCC. However, there are still many challenges in cost control, technology optimization and standardization of evaluation indicators. With the continuous progress of molecular biology technology and artificial intelligence, the application range of cfDNA in HCC diagnosis and treatment will be further expanded, its advantages will be better played, and the related shortcomings will be gradually solved.

1.	Bray F, Laversanne M, Sung H, et al. Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin, 2024, 74(3): 229-263.
2.	郝运, 李川, 文天夫, 等. 全球及中国的肝癌流行病学特征: 基于《2022全球癌症统计报告》解读. 中国普外基础与临床杂志, 2024, 31(7): 781-789.
3.	姚一菲, 孙可欣, 郑荣寿. 《2022全球癌症统计报告》解读: 中国与全球对比. 中国普外基础与临床杂志, 2024, 31(7): 769-780.
4.	中华人民共和国国家卫生健康委员会. 原发性肝癌诊疗指南(2024年版). 临床肝胆病杂志, 2024, 40(5): 893-918.
5.	Brown ZJ, Tsilimigras DI, Ruff SM, et al. Management of hepatocellular carcinoma: A review. JAMA Surg, 2023, 158(4): 410-420.
6.	Llovet JM, Kelley RK, Villanueva A, et al. Hepatocellular carcinoma. Nat Rev Dis Primers, 2021, 7(1): 6. doi: 10.1038/s41572-020-00240-3.
7.	Müller Bark J, Kulasinghe A, Chua B, et al. Circulating biomarkers in patients with glioblastoma. Br J Cancer, 2020, 122(3): 295-305.
8.	Kustanovich A, Schwartz R, Peretz T, et al. Life and death of circulating cell-free DNA. Cancer Biol Ther, 2019, 20(8): 1057-1067.
9.	Nikanjam M, Kato S, Kurzrock R. Liquid biopsy: current technology and clinical applications. J Hematol Oncol, 2022, 15(1): 131. doi: 10.1186/s13045-022-01351-y.
10.	Elazezy M, Joosse SA. Techniques of using circulating tumor DNA as a liquid biopsy component in cancer management. Comput Struct Biotechnol J, 2018, 16: 370-378.
11.	Hu Z, Chen H, Long Y, et al. The main sources of circulating cell-free DNA: Apoptosis, necrosis and active secretion. Crit Rev Oncol Hematol, 2021, 157: 103166. doi: 10.1016/j.critrevonc.2020.103166.
12.	Khier S, Gahan PB. Hepatic clearance of cell-free DNA: Possible impact on early metastasis diagnosis. Mol Diagn Ther, 2021, 25(6): 677-682.
13.	Han DSC, Ni M, Chan RWY, et al. The biology of cell-free DNA fragmentation and the roles of DNASE1, DNASE1L3, and DFFB. Am J Hum Genet, 2020, 106(2): 202-214.
14.	Han DSC, Lo YMD. The nexus of cfDNA and nuclease biology. Trends Genet, 2021, 37(8): 758-770.
15.	de Miranda FS, Claudio LMAM, de Almeida DSM, et al. Cell-free nuclear and mitochondrial DNA as potential biomarkers for assessing sepsis severity. Biomedicines, 2024, 12(5): 933. doi: 10.3390/biomedicines12050933.
16.	Berezina TA, Berezin AE. Cell-free DNA as a plausible biomarker of chronic kidney disease. Epigenomics, 2023, 15(17): 879-890.
17.	Fridlich O, Peretz A, Fox-Fisher I, et al. Elevated cfDNA after exercise is derived primarily from mature polymorphonuclear neutrophils, with a minor contribution of cardiomyocytes. Cell Rep Med, 2023, 4(6): 101074. doi: 10.1016/j.xcrm.2023.101074.
18.	Malhotra S, Miras MCM, Pappolla A, et al. Liquid biopsy in neurological diseases. Cells, 2023, 12(14): 1911. doi: 10.3390/cells12141911.
19.	Salzano A, Israr MZ, Garcia DF, et al. Circulating cell-free DNA levels are associated with adverse outcomes in heart failure: testing liquid biopsy in heart failure. Eur J Prev Cardiol, 2021, 28(9): e28-e31. doi: 10.1177/2047487320912375.
20.	Wang YH, Song Z, Hu XY, et al. Circulating tumor DNA analysis for tumor diagnosis. Talanta, 2021, 228: 122220. doi: 10.1016/j.talanta.2021.122220.
21.	Mattei AL, Bailly N, Meissner A. DNA methylation: a historical perspective. Trends Genet, 2022, 38(7): 676-707.
22.	Nguyen TH, Doan NNT, Tran TH, et al. Tissue of origin detection for cancer tumor using low-depth cfDNA samples through combination of tumor-specific methylation atlas and genome-wide methylation density in graph convolutional neural networks. J Transl Med, 2024, 22(1): 618. doi: 10.1186/s12967-024-05416-z.
23.	Qi T, Pan M, Shi H, et al. Cell-free DNA fragmentomics: The novel promising biomarker. Int J Mol Sci, 2023, 24(2): 1503. doi: 10.3390/ijms24021503.
24.	Oberhofer A, Bronkhorst AJ, Uhlig C, et al. Tracing the origin of cell-free DNA molecules through tissue-specific epigenetic signatures. Diagnostics (Basel), 2022, 12(8): 1834. doi: 10.3390/diagnostics12081834.
25.	Huang Z, Hua D, Hu Y, et al. Quantitation of plasma circulating DNA using quantitative PCR for the detection of hepatocellular carcinoma. Pathol Oncol Res, 2012, 18(2): 271-276.
26.	Piciocchi M, Cardin R, Vitale A, et al. Circulating free DNA in the progression of liver damage to hepatocellular carcinoma. Hepatol Int, 2013, 7(4): 1050-1057.
27.	Wang J, Huang A, Wang YP, et al. Circulating tumor DNA correlates with microvascular invasion and predicts tumor recurrence of hepatocellular carcinoma. Ann Transl Med, 2020, 8(5): 237. doi: 10.21037/atm.2019.12.154.
28.	Yang YJ, Chen H, Huang P, et al. Quantification of plasma hTERT DNA in hepatocellular carcinoma patients by quantitative fluorescent polymerase chain reaction. Clin Invest Med, 2011, 34(4): E238. doi: 10.25011/cim.v34i4.15366.
29.	Sogbe M, Bilbao I, Marchese FP, et al. Prognostic value of ultra-low-pass whole-genome sequencing of circulating tumor DNA in hepatocellular carcinoma under systemic treatment. Clin Mol Hepatol, 2024, 30(2): 177-190.
30.	Zhao Q, Xu Y, Yuan D, et al. Role of ssDNA as a noninvasive indicator for the diagnosis and prognosis of hepatocellular carcinoma: An exploratory study. Dis Markers, 2021, 2021: 9958909. doi: 10.1155/2021/9958909.
31.	Bian J, Long J, Yang X, et al. Construction and validation of a prognostic signature using CNV-driven genes for hepatocellular carcinoma. Ann Transl Med, 2021, 9(9): 765. doi: 10.21037/atm-20-7101.
32.	Liu F, Liao Z, Qin L, et al. Targeting VPS72 inhibits ACTL6A/MYC axis activity in HCC progression. Hepatology, 2023, 78(5): 1384-1401.
33.	Dong X, Chen G, Huang X, et al. Copy number profiling of circulating free DNA predicts transarterial chemoembolization response in advanced hepatocellular carcinoma. Mol Oncol, 2022, 16(10): 1986-1999.
34.	Molparia B, Nichani E, Torkamani A. Assessment of circulating copy number variant detection for cancer screening. PLoS One, 2017, 12(7): e0180647. doi: 10.1371/journal.pone.0180647.
35.	Draškovič T, Zidar N, Hauptman N. Circulating tumor DNA methylation biomarkers for characterization and determination of the cancer origin in malignant liver tumors. Cancers (Basel), 2023, 15(3): 859. doi: 10.3390/cancers15030859.
36.	Luo B, Ma F, Liu H, et al. Cell-free DNA methylation markers for differential diagnosis of hepatocellular carcinoma. BMC Med, 2022, 20(1): 8. doi: 10.1186/s12916-021-02201-3.
37.	Wang P, Song Q, Ren J, et al. Simultaneous analysis of mutations and methylations in circulating cell-free DNA for hepatocellular carcinoma detection. Sci Transl Med, 2022, 14(672): eabp8704. doi: 10.1126/scitranslmed.abp8704.
38.	Tseng CF, Chen LT, Wang HD, et al. Transcriptional suppression of Dicer by HOXB-AS3/EZH2 complex dictates sorafenib resistance and cancer stemness. Cancer Sci, 2022, 113(5): 1601-1612.
39.	Lai Y, Han X, Xie B, et al. EZH2 suppresses ferroptosis in hepatocellular carcinoma and reduces sorafenib sensitivity through epigenetic regulation of TFR2. Cancer Sci, 2024, 115(7): 2220-2234.
40.	Cui Y, Li H, Zhan H, et al. Identification of Potential Biomarkers for Liver Cancer Through Gene Mutation and Clinical Characteristics. Front Oncol, 2021, 11: 733478. doi: 10.3389/fonc.2021.733478.
41.	Kusakabe Y, Chiba T, Oshima M, et al. EZH1/2 inhibition augments the anti-tumor effects of sorafenib in hepatocellular carcinoma. Sci Rep, 2021, 11(1): 21396. doi: 10.1038/s41598-021-00889-0.
42.	Zhang L, Li HT, Shereda R, et al. DNMT and EZH2 inhibitors synergize to activate therapeutic targets in hepatocellular carcinoma. Cancer Lett, 2022, 548: 215899. doi: 10.1016/j.canlet.2022.215899.
43.	Cowzer D, White JB, Chou JF, et al. Targeted molecular profiling of circulating cell-free DNA in patients with advanced hepatocellular carcinoma. JCO Precis Oncol, 2023, 7: e2300272. doi: 10.1200/PO.23.00272.
44.	Zhao W, Qiu L, Liu H, et al. Circulating tumor DNA as a potential prognostic and predictive biomarker during interventional therapy of unresectable primary liver cancer. J Gastrointest Oncol, 2020, 11(5): 1065-1077.
45.	Kaseb AO, Sánchez NS, Sen S, et al. Molecular profiling of hepatocellular carcinoma using circulating cell-free DNA. Clin Cancer Res, 2019, 25(20): 6107-6118.
46.	Toh MR, Wong EYT, Wong SH, et al. Global Epidemiology and Genetics of Hepatocellular Carcinoma. Gastroenterology, 2023, 164(5): 766-782.
47.	Wang S, Shi H, Liu T, et al. Mutation profile and its correlation with clinicopathology in Chinese hepatocellular carcinoma patients. Hepatobiliary Surg Nutr, 2021, 10(2): 172-179.
48.	Hassin O, Oren M. Drugging p53 in cancer: one protein, many targets. Nat Rev Drug Discov, 2023, 22(2): 127-144.
49.	Wang Z, Li Z, Ji H. Direct targeting of β-catenin in the Wnt signaling pathway: Current progress and perspectives. Med Res Rev, 2021, 41(4): 2109-2129.
50.	Wang H, Guo M, Wei H, et al. Targeting p53 pathways: mechanisms, structures, and advances in therapy. Signal Transduct Target Ther, 2023, 8(1): 92. doi: 10.1038/s41392-023-01347-1.
51.	Fu Y, Yang Z, Hu Z, et al. Preoperative serum ctDNA predicts early hepatocellular carcinoma recurrence and response to systemic therapies. Hepatol Int, 2022, 16(4): 868-878.
52.	Matsumae T, Kodama T, Myojin Y, et al. Circulating cell-free DNA profiling predicts the therapeutic outcome in advanced hepatocellular carcinoma patients treated with combination immunotherapy. Cancers (Basel), 2022, 14(14): 3367. doi: 10.3390/cancers14143367.
53.	Vendrell JA, Mau-Them FT, Béganton B, et al. Circulating cell free tumor DNA detection as a routine tool for lung cancer patient management. Int J Mol Sci, 2017, 18(2): 264. doi: 10.3390/ijms18020264.
54.	Song P, Wu LR, Yan YH, et al. Limitations and opportunities of technologies for the analysis of cell-free DNA in cancer diagnostics. Nat Biomed Eng, 2022, 6(3): 232-245.
55.	孙同正, 杨芳. 基于实时荧光定量聚合酶链反应技术预测龋病发生的研究进展. 口腔医学研究, 2019, 35(1): 13-15.
56.	Rausch C, Rothenberg-Thurley M, Buerger SA, et al. Double drop-off droplet digital PCR: A novel, versatile tool for mutation screening and residual disease monitoring in acute myeloid leukemia using cellular or cell-free DNA. J Mol Diagn, 2021, 23(8): 975-985.
57.	Palacín-Aliana I, García-Romero N, Asensi-Puig A, et al. Clinical utility of liquid biopsy-based actionable mutations detected via ddPCR. Biomedicines, 2021, 9(8): 906. doi: 10.3390/biomedicines9080906.
58.	Kojabad AA, Farzanehpour M, Galeh HEG, et al. Droplet digital PCR of viral ‎DNA/RNA, current progress, challenges, and future perspectives. J Med Virol, 2021, 93(7): 4182-4197.
59.	García-Foncillas J, Alba E, Aranda E, et al. Incorporating BEAMing technology as a liquid biopsy into clinical practice for the management of colorectal cancer patients: an expert taskforce review. Ann Oncol, 2017, 28(12): 2943-2949.
60.	Diehl F, Schmidt K, Choti MA, et al. Circulating mutant DNA to assess tumor dynamics. Nat Med, 2008, 14(9): 985-990.
61.	Katsuya Y. Current and future trends in whole genome sequencing in cancer. Cancer Biol Med, 2024, 21(1): 16-20.
62.	Brlek P, Bulić L, Bračić M, et al. Implementing whole genome sequencing (WGS) in clinical practice: Advantages, challenges, and future perspectives. Cells, 2024, 13(6): 504. doi: 10.3390/cells13060504.
63.	Hansen MC, Haferlach T, Nyvold CG. A decade with whole exome sequencing in haematology. Br J Haematol, 2020, 188(3): 367-382.

1. Bray F, Laversanne M, Sung H, et al. Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin, 2024, 74(3): 229-263.
2. 郝运, 李川, 文天夫, 等. 全球及中国的肝癌流行病学特征: 基于《2022全球癌症统计报告》解读. 中国普外基础与临床杂志, 2024, 31(7): 781-789.
3. 姚一菲, 孙可欣, 郑荣寿. 《2022全球癌症统计报告》解读: 中国与全球对比. 中国普外基础与临床杂志, 2024, 31(7): 769-780.
4. 中华人民共和国国家卫生健康委员会. 原发性肝癌诊疗指南(2024年版). 临床肝胆病杂志, 2024, 40(5): 893-918.
5. Brown ZJ, Tsilimigras DI, Ruff SM, et al. Management of hepatocellular carcinoma: A review. JAMA Surg, 2023, 158(4): 410-420.
6. Llovet JM, Kelley RK, Villanueva A, et al. Hepatocellular carcinoma. Nat Rev Dis Primers, 2021, 7(1): 6. doi: 10.1038/s41572-020-00240-3.
7. Müller Bark J, Kulasinghe A, Chua B, et al. Circulating biomarkers in patients with glioblastoma. Br J Cancer, 2020, 122(3): 295-305.
8. Kustanovich A, Schwartz R, Peretz T, et al. Life and death of circulating cell-free DNA. Cancer Biol Ther, 2019, 20(8): 1057-1067.
9. Nikanjam M, Kato S, Kurzrock R. Liquid biopsy: current technology and clinical applications. J Hematol Oncol, 2022, 15(1): 131. doi: 10.1186/s13045-022-01351-y.
10. Elazezy M, Joosse SA. Techniques of using circulating tumor DNA as a liquid biopsy component in cancer management. Comput Struct Biotechnol J, 2018, 16: 370-378.
11. Hu Z, Chen H, Long Y, et al. The main sources of circulating cell-free DNA: Apoptosis, necrosis and active secretion. Crit Rev Oncol Hematol, 2021, 157: 103166. doi: 10.1016/j.critrevonc.2020.103166.
12. Khier S, Gahan PB. Hepatic clearance of cell-free DNA: Possible impact on early metastasis diagnosis. Mol Diagn Ther, 2021, 25(6): 677-682.
13. Han DSC, Ni M, Chan RWY, et al. The biology of cell-free DNA fragmentation and the roles of DNASE1, DNASE1L3, and DFFB. Am J Hum Genet, 2020, 106(2): 202-214.
14. Han DSC, Lo YMD. The nexus of cfDNA and nuclease biology. Trends Genet, 2021, 37(8): 758-770.
15. de Miranda FS, Claudio LMAM, de Almeida DSM, et al. Cell-free nuclear and mitochondrial DNA as potential biomarkers for assessing sepsis severity. Biomedicines, 2024, 12(5): 933. doi: 10.3390/biomedicines12050933.
16. Berezina TA, Berezin AE. Cell-free DNA as a plausible biomarker of chronic kidney disease. Epigenomics, 2023, 15(17): 879-890.
17. Fridlich O, Peretz A, Fox-Fisher I, et al. Elevated cfDNA after exercise is derived primarily from mature polymorphonuclear neutrophils, with a minor contribution of cardiomyocytes. Cell Rep Med, 2023, 4(6): 101074. doi: 10.1016/j.xcrm.2023.101074.
18. Malhotra S, Miras MCM, Pappolla A, et al. Liquid biopsy in neurological diseases. Cells, 2023, 12(14): 1911. doi: 10.3390/cells12141911.
19. Salzano A, Israr MZ, Garcia DF, et al. Circulating cell-free DNA levels are associated with adverse outcomes in heart failure: testing liquid biopsy in heart failure. Eur J Prev Cardiol, 2021, 28(9): e28-e31. doi: 10.1177/2047487320912375.
20. Wang YH, Song Z, Hu XY, et al. Circulating tumor DNA analysis for tumor diagnosis. Talanta, 2021, 228: 122220. doi: 10.1016/j.talanta.2021.122220.
21. Mattei AL, Bailly N, Meissner A. DNA methylation: a historical perspective. Trends Genet, 2022, 38(7): 676-707.
22. Nguyen TH, Doan NNT, Tran TH, et al. Tissue of origin detection for cancer tumor using low-depth cfDNA samples through combination of tumor-specific methylation atlas and genome-wide methylation density in graph convolutional neural networks. J Transl Med, 2024, 22(1): 618. doi: 10.1186/s12967-024-05416-z.
23. Qi T, Pan M, Shi H, et al. Cell-free DNA fragmentomics: The novel promising biomarker. Int J Mol Sci, 2023, 24(2): 1503. doi: 10.3390/ijms24021503.
24. Oberhofer A, Bronkhorst AJ, Uhlig C, et al. Tracing the origin of cell-free DNA molecules through tissue-specific epigenetic signatures. Diagnostics (Basel), 2022, 12(8): 1834. doi: 10.3390/diagnostics12081834.
25. Huang Z, Hua D, Hu Y, et al. Quantitation of plasma circulating DNA using quantitative PCR for the detection of hepatocellular carcinoma. Pathol Oncol Res, 2012, 18(2): 271-276.
26. Piciocchi M, Cardin R, Vitale A, et al. Circulating free DNA in the progression of liver damage to hepatocellular carcinoma. Hepatol Int, 2013, 7(4): 1050-1057.
27. Wang J, Huang A, Wang YP, et al. Circulating tumor DNA correlates with microvascular invasion and predicts tumor recurrence of hepatocellular carcinoma. Ann Transl Med, 2020, 8(5): 237. doi: 10.21037/atm.2019.12.154.
28. Yang YJ, Chen H, Huang P, et al. Quantification of plasma hTERT DNA in hepatocellular carcinoma patients by quantitative fluorescent polymerase chain reaction. Clin Invest Med, 2011, 34(4): E238. doi: 10.25011/cim.v34i4.15366.
29. Sogbe M, Bilbao I, Marchese FP, et al. Prognostic value of ultra-low-pass whole-genome sequencing of circulating tumor DNA in hepatocellular carcinoma under systemic treatment. Clin Mol Hepatol, 2024, 30(2): 177-190.
30. Zhao Q, Xu Y, Yuan D, et al. Role of ssDNA as a noninvasive indicator for the diagnosis and prognosis of hepatocellular carcinoma: An exploratory study. Dis Markers, 2021, 2021: 9958909. doi: 10.1155/2021/9958909.
31. Bian J, Long J, Yang X, et al. Construction and validation of a prognostic signature using CNV-driven genes for hepatocellular carcinoma. Ann Transl Med, 2021, 9(9): 765. doi: 10.21037/atm-20-7101.
32. Liu F, Liao Z, Qin L, et al. Targeting VPS72 inhibits ACTL6A/MYC axis activity in HCC progression. Hepatology, 2023, 78(5): 1384-1401.
33. Dong X, Chen G, Huang X, et al. Copy number profiling of circulating free DNA predicts transarterial chemoembolization response in advanced hepatocellular carcinoma. Mol Oncol, 2022, 16(10): 1986-1999.
34. Molparia B, Nichani E, Torkamani A. Assessment of circulating copy number variant detection for cancer screening. PLoS One, 2017, 12(7): e0180647. doi: 10.1371/journal.pone.0180647.
35. Draškovič T, Zidar N, Hauptman N. Circulating tumor DNA methylation biomarkers for characterization and determination of the cancer origin in malignant liver tumors. Cancers (Basel), 2023, 15(3): 859. doi: 10.3390/cancers15030859.
36. Luo B, Ma F, Liu H, et al. Cell-free DNA methylation markers for differential diagnosis of hepatocellular carcinoma. BMC Med, 2022, 20(1): 8. doi: 10.1186/s12916-021-02201-3.
37. Wang P, Song Q, Ren J, et al. Simultaneous analysis of mutations and methylations in circulating cell-free DNA for hepatocellular carcinoma detection. Sci Transl Med, 2022, 14(672): eabp8704. doi: 10.1126/scitranslmed.abp8704.
38. Tseng CF, Chen LT, Wang HD, et al. Transcriptional suppression of Dicer by HOXB-AS3/EZH2 complex dictates sorafenib resistance and cancer stemness. Cancer Sci, 2022, 113(5): 1601-1612.
39. Lai Y, Han X, Xie B, et al. EZH2 suppresses ferroptosis in hepatocellular carcinoma and reduces sorafenib sensitivity through epigenetic regulation of TFR2. Cancer Sci, 2024, 115(7): 2220-2234.
40. Cui Y, Li H, Zhan H, et al. Identification of Potential Biomarkers for Liver Cancer Through Gene Mutation and Clinical Characteristics. Front Oncol, 2021, 11: 733478. doi: 10.3389/fonc.2021.733478.
41. Kusakabe Y, Chiba T, Oshima M, et al. EZH1/2 inhibition augments the anti-tumor effects of sorafenib in hepatocellular carcinoma. Sci Rep, 2021, 11(1): 21396. doi: 10.1038/s41598-021-00889-0.
42. Zhang L, Li HT, Shereda R, et al. DNMT and EZH2 inhibitors synergize to activate therapeutic targets in hepatocellular carcinoma. Cancer Lett, 2022, 548: 215899. doi: 10.1016/j.canlet.2022.215899.
43. Cowzer D, White JB, Chou JF, et al. Targeted molecular profiling of circulating cell-free DNA in patients with advanced hepatocellular carcinoma. JCO Precis Oncol, 2023, 7: e2300272. doi: 10.1200/PO.23.00272.
44. Zhao W, Qiu L, Liu H, et al. Circulating tumor DNA as a potential prognostic and predictive biomarker during interventional therapy of unresectable primary liver cancer. J Gastrointest Oncol, 2020, 11(5): 1065-1077.
45. Kaseb AO, Sánchez NS, Sen S, et al. Molecular profiling of hepatocellular carcinoma using circulating cell-free DNA. Clin Cancer Res, 2019, 25(20): 6107-6118.
46. Toh MR, Wong EYT, Wong SH, et al. Global Epidemiology and Genetics of Hepatocellular Carcinoma. Gastroenterology, 2023, 164(5): 766-782.
47. Wang S, Shi H, Liu T, et al. Mutation profile and its correlation with clinicopathology in Chinese hepatocellular carcinoma patients. Hepatobiliary Surg Nutr, 2021, 10(2): 172-179.
48. Hassin O, Oren M. Drugging p53 in cancer: one protein, many targets. Nat Rev Drug Discov, 2023, 22(2): 127-144.
49. Wang Z, Li Z, Ji H. Direct targeting of β-catenin in the Wnt signaling pathway: Current progress and perspectives. Med Res Rev, 2021, 41(4): 2109-2129.
50. Wang H, Guo M, Wei H, et al. Targeting p53 pathways: mechanisms, structures, and advances in therapy. Signal Transduct Target Ther, 2023, 8(1): 92. doi: 10.1038/s41392-023-01347-1.
51. Fu Y, Yang Z, Hu Z, et al. Preoperative serum ctDNA predicts early hepatocellular carcinoma recurrence and response to systemic therapies. Hepatol Int, 2022, 16(4): 868-878.
52. Matsumae T, Kodama T, Myojin Y, et al. Circulating cell-free DNA profiling predicts the therapeutic outcome in advanced hepatocellular carcinoma patients treated with combination immunotherapy. Cancers (Basel), 2022, 14(14): 3367. doi: 10.3390/cancers14143367.
53. Vendrell JA, Mau-Them FT, Béganton B, et al. Circulating cell free tumor DNA detection as a routine tool for lung cancer patient management. Int J Mol Sci, 2017, 18(2): 264. doi: 10.3390/ijms18020264.
54. Song P, Wu LR, Yan YH, et al. Limitations and opportunities of technologies for the analysis of cell-free DNA in cancer diagnostics. Nat Biomed Eng, 2022, 6(3): 232-245.
55. 孙同正, 杨芳. 基于实时荧光定量聚合酶链反应技术预测龋病发生的研究进展. 口腔医学研究, 2019, 35(1): 13-15.
56. Rausch C, Rothenberg-Thurley M, Buerger SA, et al. Double drop-off droplet digital PCR: A novel, versatile tool for mutation screening and residual disease monitoring in acute myeloid leukemia using cellular or cell-free DNA. J Mol Diagn, 2021, 23(8): 975-985.
57. Palacín-Aliana I, García-Romero N, Asensi-Puig A, et al. Clinical utility of liquid biopsy-based actionable mutations detected via ddPCR. Biomedicines, 2021, 9(8): 906. doi: 10.3390/biomedicines9080906.
58. Kojabad AA, Farzanehpour M, Galeh HEG, et al. Droplet digital PCR of viral ‎DNA/RNA, current progress, challenges, and future perspectives. J Med Virol, 2021, 93(7): 4182-4197.
59. García-Foncillas J, Alba E, Aranda E, et al. Incorporating BEAMing technology as a liquid biopsy into clinical practice for the management of colorectal cancer patients: an expert taskforce review. Ann Oncol, 2017, 28(12): 2943-2949.
60. Diehl F, Schmidt K, Choti MA, et al. Circulating mutant DNA to assess tumor dynamics. Nat Med, 2008, 14(9): 985-990.
61. Katsuya Y. Current and future trends in whole genome sequencing in cancer. Cancer Biol Med, 2024, 21(1): 16-20.
62. Brlek P, Bulić L, Bračić M, et al. Implementing whole genome sequencing (WGS) in clinical practice: Advantages, challenges, and future perspectives. Cells, 2024, 13(6): 504. doi: 10.3390/cells13060504.
63. Hansen MC, Haferlach T, Nyvold CG. A decade with whole exome sequencing in haematology. Br J Haematol, 2020, 188(3): 367-382.

CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Latest ArticlesResearch progress on application of circulating free DNA in diagnosis and treatment of hepatocellular carcinoma

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