循环肿瘤DNA在肝细胞癌中的研究现状及展望

侯志远; 刘源; 杨超然; 赵继森; 程树杰

doi:10.3969/j.issn.1001-5256.2022.11.036

循环肿瘤DNA在肝细胞癌中的研究现状及展望

DOI: 10.3969/j.issn.1001-5256.2022.11.036

河北大学附属医院肝胆外科，河北保定 071000

基金项目:

河北省自然科学基金 (18277790D)

利益冲突声明：所有作者均声明不存在利益冲突。

作者贡献声明：侯志远负责课题设计，资料分析，撰写论文；刘源、杨超然参与收集数据，修改论文；赵继森、程树杰负责拟定写作思路，指导撰写文章并最后定稿。

详细信息

通信作者:
程树杰，chengshuj@126.com

计量
- 文章访问数: 507
- HTML全文浏览量: 254
- PDF下载量: 56
- 被引次数: 0
出版历程
- 收稿日期: 2022-04-01
- 录用日期: 2022-06-30
- 出版日期: 2022-11-20

Current research status and prospect of circulating tumor DNA in hepatocellular carcinoma

Department of Hepatobiliary Surgery, Affiliated Hospital of Hebei University, Baoding, Hebei 071000, China

Research funding:

Natural Science Foundation of Hebei Province (18277790D)

More Information

Corresponding author: CHENG Shujie, chengshuj@126.com (ORCID: 0000-0003-2646-3938)

摘要

摘要: 肝细胞癌(HCC)是世界范围内最常见的恶性肿瘤之一，具有起病隐匿、手术切除率低、易早期转移和复发的特点。近年来，随着新的分子生物学技术的发展，一种液体活检技术——循环肿瘤DNA(ctDNA)检测取得了鼓舞人心的成果。本文综述了ctDNA作为HCC患者液体活检的关键成分的研究现状及未来展望，以期为HCC的临床治疗提供新思路。
- 癌, 肝细胞 /
- 肿瘤细胞, 循环 /
- DNA
Abstract: Hepatocellular carcinoma (HCC) is one of the most common malignant tumors in the world, with the features of insidious onset, low surgical resection rate, and frequent early metastasis and recurrence. With the development of new molecular biology technology in recent years, a liquid biopsy technology, circulating tumor DNA (ctDNA) detection, has achieved encouraging results. This article reviews the current research status and future prospects of ctDNA as a key component of liquid biopsy in patients with HCC, in order to provide new ideas for the clinical treatment of HCC.
- Carcinoma, Hepatocellular /
- Neoplastic Cells, Circulating /
- DNA

HTML全文

参考文献(51)

[1]	SUNG H, FERLAY J, SIEGEL RL, et al. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries[J]. CA Cancer J Clin, 2021, 71(3): 209-249. DOI: 10.3322/caac.21660.
[2]	BEI C, TAN C, ZHU X, et al. Association between polymorphisms in CMTM family genes and hepatocellular carcinoma in Guangxi of China[J]. DNA Cell Biol, 2018, 37(8): 691-696. DOI: 10.1089/dna.2018.4274.
[3]	NG C, di COSTANZO GG, TERRACCIANO LM, et al. Circulating cell-free DNA in hepatocellular carcinoma: current insights and outlook[J]. Front Med (Lausanne), 2018, 5: 78. DOI: 10.3389/fmed.2018.00078.
[4]	LLOVET JM, MONTAL R, SIA D, et al. Molecular therapies and precision medicine for hepatocellular carcinoma[J]. Nat Rev Clin Oncol, 2018, 15(10): 599-616. DOI: 10.1038/s41571-018-0073-4.
[5]	General Office of National Health Commission. Standard for diagnosis and treatment of primary liver cancer (2022 edition)[J]. J Clin Hepatol, 2022, 38(2): 288-303. DOI: 10.3969/j.issn.1001-5256.2022.02.009. 国家卫生健康委办公厅. 原发性肝癌诊疗指南(2022年版)[J]. 临床肝胆病杂志, 2022, 38(2): 288-303. DOI: 10.3969/j.issn.1001-5256.2022.02.009.
[6]	VILLANUEVA A. Hepatocellular carcinoma[J]. N Engl J Med, 2019, 380(15): 1450-1462. DOI: 10.1056/NEJMra1713263.
[7]	ALIX-PANABIÈRES C, PANTEL K. Clinical applications of circulating tumor cells and circulating tumor DNA as Liquid Biopsy[J]. Cancer Discov, 2016, 6(5): 479-491. DOI: 10.1158/2159-8290.CD-15-1483.
[8]	CORCORAN RB, CHABNER BA. Application of cell-free DNA analysis to cancer treatment[J]. N Engl J Med, 2018, 379(18): 1754-1765. DOI: 10.1056/NEJMra1706174.
[9]	MANDEL P, METAIS P. Nuclear acids in human blood plasma[J]. C R Seances Soc Biol Fil, 1948, 142(3-4): 241-243.
[10]	LEON SA, SHAPIRO B, SKLAROFF DM, et al. Free DNA in the serum of cancer patients and the effect of therapy[J]. Cancer Res, 1977, 37(3): 646-650.
[11]	PESSOA LS, HERINGER M, FERRER VP. ctDNA as a cancer biomarker: A broad overview[J]. Crit Rev Oncol Hematol, 2020, 155: 103109. DOI: 10.1016/j.critrevonc.2020.103109.
[12]	KASEB AO, SÁNCHEZ NS, SEN S, et al. Molecular profiling of hepatocellular carcinoma using circulating cell-free DNA[J]. Clin Cancer Res, 2019, 25(20): 6107-6118. DOI: 10.1158/1078-0432.CCR-18-3341.
[13]	WANG M, YE Q, MAO D, et al. Research progress in liver-regenerating microenvironment and DNA methylation in hepatocellular carcinoma: the role of Traditional Chinese Medicine[J]. Med Sci Monit, 2020, 26: e920310. DOI: 10.12659/MSM.920310.
[14]	HEITZER E, HAQUE IS, ROBERTS C, et al. Current and future perspectives of liquid biopsies in genomics-driven oncology[J]. Nat Rev Genet, 2019, 20(2): 71-88. DOI: 10.1038/s41576-018-0071-5.
[15]	von FELDEN J. New systemic agents for hepatocellular carcinoma: an update 2020[J]. Curr Opin Gastroenterol, 2020, 36(3): 177-183. DOI: 10.1097/MOG.0000000000000626.
[16]	ZHU AX, KANG YK, YEN CJ, et al. Ramucirumab after sorafenib in patients with advanced hepatocellular carcinoma and increased α-fetoprotein concentrations (REACH-2): a randomised, double-blind, placebo-controlled, phase 3 trial[J]. Lancet Oncol, 2019, 20(2): 282-296. DOI: 10.1016/S1470-2045(18)30937-9.
[17]	von FELDEN J, CRAIG AJ, GARCIA-LEZANA T, et al. Mutations in circulating tumor DNA predict primary resistance to systemic therapies in advanced hepatocellular carcinoma[J]. Oncogene, 2021, 40(1): 140-151. DOI: 10.1038/s41388-020-01519-1.
[18]	REDDY T, ESMAIL A, CHANG JC, et al. Utility of cell-free DNA Detection in transplant oncology[J]. Cancers (Basel), 2022, 14(3): 743. DOI: 10.3390/cancers14030743.
[19]	NG HI, ZHU X, XUAN L, et al. Analysis of fragment size distribution of cell-free DNA: A potential non-invasive marker to monitor graft damage in living-related liver transplantation for inborn errors of metabolism[J]. Mol Genet Metab, 2019, 127(1): 45-50. DOI: 10.1016/j.ymgme.2019.03.004.
[20]	OKAJIMA W, KOMATSU S, ICHIKAWA D, et al. Liquid biopsy in patients with hepatocellular carcinoma: Circulating tumor cells and cell-free nucleic acids[J]. World J Gastroenterol, 2017, 23(31): 5650-5668. DOI: 10.3748/wjg.v23.i31.5650.
[21]	CHEN VL, XU D, WICHA MS, et al. Utility of liquid biopsy analysis in detection of hepatocellular carcinoma, determination of prognosis, and disease monitoring: A Systematic Review[J]. Clin Gastroenterol Hepatol, 2020, 18(13): 2879-2902. e9. DOI: 10.1016/j.cgh.2020.04.019.
[22]	WENG J, ATYAH M, ZHOU C, et al. Prospects and challenges of circulating tumor DNA in precision medicine of hepatocellular carcinoma[J]. Clin Exp Med, 2020, 20(3): 329-337. DOI: 10.1007/s10238-020-00620-9.
[23]	MOHAMED NA, SWIFY EM, AMIN NF, et al. Is serum level of methylated RASSF1A valuable in diagnosing hepatocellular carcinoma in patients with chronic viral hepatitis C?[J]. Arab J Gastroenterol, 2012, 13(3): 111-115. DOI: 10.1016/j.ajg.2012.06.009.
[24]	ZUCMAN-ROSSI J, VILLANUEVA A, NAULT JC, et al. Genetic landscape and biomarkers of hepatocellular carcinoma[J]. Gastroenterology, 2015, 149(5): 1226-1239. e4. DOI: 10.1053/j.gastro.2015.05.061.
[25]	CAI ZX, CHEN G, ZENG YY, et al. Circulating tumor DNA profiling reveals clonal evolution and real-time disease progression in advanced hepatocellular carcinoma[J]. Int J Cancer, 2017, 141(5): 977-985. DOI: 10.1002/ijc.30798.
[26]	CAI Z, CHEN G, ZENG Y, et al. Comprehensive liquid profiling of circulating tumor DNA and protein biomarkers in long-term follow-up patients with hepatocellular carcinoma[J]. Clin Cancer Res, 2019, 25(17): 5284-5294. DOI: 10.1158/1078-0432.CCR-18-3477.
[27]	GARCÍA-FERNÁNDEZ N, MACHER HC, RUBIO A, et al. Detection of p53 mutations in circulating DNA of transplanted hepatocellular carcinoma patients as a biomarker of tumor recurrence[J]. Adv Exp Med Biol, 2016, 924: 25-28. DOI: 10.1007/978-3-319-42044-8_5.
[28]	ZOU YN, YUAN XL. Application value of immunotherapy in hepatocellular carcinoma[J]. J Clin Hepatol, 2021, 37(8): 1758-1760. DOI: 10.3969/j.issn.1001-5256.2021.08.004. 邹燕梅, 袁响林. 免疫治疗在肝细胞癌中的应用价值[J]. 临床肝胆病杂志, 2021, 37(8): 1758-1760. DOI: 10.3969/j.issn.1001-5256.2021.08.004.
[29]	LI F, QIAO CY, GAO S, et al. Circulating cell-free DNA of methylated insulin-like growth factor-binding protein 7 predicts a poor prognosis in hepatitis B virus-associated hepatocellular carcinoma after hepatectomy[J]. Free Radic Res, 2018, 52(4): 455-464. DOI: 10.1080/10715762.2018.1443448.
[30]	CHAN KC, LAI PB, MOK TS, et al. Quantitative analysis of circulating methylated DNA as a biomarker for hepatocellular carcinoma[J]. Clin Chem, 2008, 54(9): 1528-1536. DOI: 10.1373/clinchem.2008.104653.
[31]	WONG IH, LO YM, YEO W, et al. Frequent p15 promoter methylation in tumor and peripheral blood from hepatocellular carcinoma patients[J]. Clin Cancer Res, 2000, 6(9): 3516-3521.
[32]	TANGKIJVANICH P, HOURPAI N, RATTANATANYONG P, et al. Serum LINE-1 hypomethylation as a potential prognostic marker for hepatocellular carcinoma[J]. Clin Chim Acta, 2007, 379(1-2): 127-133. DOI: 10.1016/j.cca.2006.12.029.
[33]	HARDING JJ, NANDAKUMAR S, ARMENIA J, et al. Prospective genotyping of hepatocellular carcinoma: Clinical implications of next-generation sequencing for matching patients to targeted and immune therapies[J]. Clin Cancer Res, 2019, 25(7): 2116-2126. DOI: 10.1158/1078-0432.CCR-18-2293.
[34]	ZHANG ZC, SUN LC, SUN QY, et al. Global research hotspots and trends in the field of immunotherapy for liver cancer in 2011-2020 based on CiteSpace analysis[J]. J Clin Hepatol, 2021, 37(12): 2843-2848. DOI: 10.3969/j.issn.1001-5256.2021.12.022. 张稚淳, 孙力超, 孙秋月, 等. 基于CiteSpace分析2011年-2020年全球肝癌免疫治疗研究领域的热点及趋势[J]. 临床肝胆病杂志, 2021, 37(12): 2843-2848. DOI: 10.3969/j.issn.1001-5256.2021.12.022.
[35]	ZHANG Y, LIU Z, JI K, et al. Clinical application value of circulating cell-free DNA in hepatocellular carcinoma[J]. Front Mol Biosci, 2021, 8: 736330. DOI: 10.3389/fmolb.2021.736330.
[36]	CHAN SL, WONG AM, LEE K, et al. Personalized therapy for hepatocellular carcinoma: Where are we now?[J]. Cancer Treat Rev, 2016, 45: 77-86. DOI: 10.1016/j.ctrv.2016.02.008.
[37]	SCHWAEDERLÉ M, LAZAR V, VALIDIRE P, et al. VEGF-A expression correlates with TP53 mutations in non-small cell lung cancer: Implications for antiangiogenesis therapy[J]. Cancer Res, 2015, 75(7): 1187-1190. DOI: 10.1158/0008-5472.CAN-14-2305.
[38]	CHANG Y, TOLANI B, NIE X, et al. Review of the clinical applications and technological advances of circulating tumor DNA in cancer monitoring[J]. Ther Clin Risk Manag, 2017, 13: 1363-1374. DOI: 10.2147/TCRM.S141991.
[39]	IKEDA S, TSIGELNY IF, SKJEVIK ÅA, et al. Next-generation sequencing of circulating tumor DNA reveals frequent alterations in advanced hepatocellular carcinoma[J]. Oncologist, 2018, 23(5): 586-593. DOI: 10.1634/theoncologist.2017-0479.
[40]	LIM HY, MERLE P, WEISS KH, et al. Phase Ⅱ studies with refametinib or refametinib plus sorafenib in patients with RAS-mutated hepatocellular carcinoma[J]. Clin Cancer Res, 2018, 24(19): 4650-4661. DOI: 10.1158/1078-0432.CCR-17-3588.
[41]	GALLE E, THIENPONT B, CAPPUYNS S, et al. DNA methylation-driven EMT is a common mechanism of resistance to various therapeutic agents in cancer[J]. Clin Epigenetics, 2020, 12(1): 27. DOI: 10.1186/s13148-020-0821-z.
[42]	JIN Y, CHEN DL, WANG F, et al. The predicting role of circulating tumor DNA landscape in gastric cancer patients treated with immune checkpoint inhibitors[J]. Mol Cancer, 2020, 19(1): 154. DOI: 10.1186/s12943-020-01274-7.
[43]	LIU YY. New progress of hepatocellular carcinoma treatment[J]. Chin J Dig Surg, 2022, 21(1): 15-18. DOI: 10.3760/cma.j.cn115610-20220107-00020. 刘允怡. 肝细胞癌治疗的新发展[J]. 中华消化外科杂志, 2022, 21(1): 15-18. DOI: 10.3760/cma.j.cn115610-20220107-00020.
[44]	BRUIX J, SHERMAN M, American association for the study of liver diseases. Management of hepatocellular carcinoma: an update[J]. Hepatology, 2011, 53(3): 1020-1022. DOI: 10.1002/hep.24199.
[45]	VOSO MT, OTTONE T, LAVORGNA S, et al. MRD in AML: The role of new techniques[J]. Front Oncol, 2019, 9: 655. DOI: 10.3389/fonc.2019.00655.
[46]	SCHUURHUIS GJ, HEUSER M, FREEMAN S, et al. Minimal/measurable residual disease in AML: a consensus document from the European LeukemiaNet MRD Working Party[J]. Blood, 2018, 131(12): 1275-1291. DOI: 10.1182/blood-2017-09-801498.
[47]	WANG J, HUANG A, WANG YP, et al. Circulating tumor DNA correlates with microvascular invasion and predicts tumor recurrence of hepatocellular carcinoma[J]. Ann Transl Med, 2020, 8(5): 237. DOI: 10.21037/atm.2019.12.154.
[48]	LEE TH, MONTALVO L, CHREBTOW V, et al. Quantitation of genomic DNA in plasma and serum samples: higher concentrations of genomic DNA found in serum than in plasma[J]. Transfusion, 2001, 41(2): 276-282. DOI: 10.1046/j.1537-2995.2001.41020276.x.
[49]	HU Y, ULRICH BC, SUPPLEE J, et al. False-positive plasma genotyping due to clonal hematopoiesis[J]. Clin Cancer Res, 2018, 24(18): 4437-4443. DOI: 10.1158/1078-0432.CCR-18-0143.
[50]	YANG YC, WANG D, JIN L, et al. Circulating tumor DNA detectable in early-and late-stage colorectal cancer patients[J]. Biosci Rep, 2018, 38(4): BSR20180322. DOI: 10.1042/BSR20180322.
[51]	DHAYAT SA, YANG Z. Impact of circulating tumor DNA in hepatocellular and pancreatic carcinomas[J]. J Cancer Res Clin Oncol, 2020, 146(7): 1625-1645. DOI: 10.1007/s00432-020-03219-5.