中文English
ISSN 1001-5256 (Print)
ISSN 2097-3497 (Online)
CN 22-1108/R

留言板

尊敬的读者、作者、审稿人, 关于本刊的投稿、审稿、编辑和出版的任何问题, 您可以本页添加留言。我们将尽快给您答复。谢谢您的支持!

姓名
邮箱
手机号码
标题
留言内容
验证码

早期肝癌无创诊断之匙——循环游离DNA联合型液体活检

叶婷丹 雷学忠

引用本文:
Citation:

早期肝癌无创诊断之匙——循环游离DNA联合型液体活检

DOI: 10.3969/j.issn.1001-5256.2022.04.037
基金项目: 

“十三五”国家科技重大专项 (2017ZX10202203-008-005)

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:叶婷丹对研究的思路或设计有关键贡献,参与了研究数据的获取分析解释过程,参与起草或修改文章关键内容; 雷学忠负责指导撰写文章并最后定稿。
详细信息
    通信作者:

    雷学忠,18980601317@163.com

Circulating cell-free DNA-combined liquid biopsy: The key to noninvasive diagnosis of early-stage liver cancer

Research funding: 

National Major Scientific and Technological Special Project during the Thirteenth Five-year Plan Period (2017ZX10202203-008-005)

More Information
  • 摘要: 循环游离DNA(cfDNA)被认为是诊断早期肝癌极具研究前景的液体活检切入点。但不少研究证实单独使用cfDNA作为检测指标其诊断效能缺乏稳定性,尤其是单纯定量分析并不能很好地反映肿瘤情况。而更多研究表示cfDNA适宜多指标联合检测或与其他肝癌诊断标志物进行联合检测。本文回顾了截至2021年7月以cfDNA为出发点的联合型液体活检相关文献,归纳了现有研究中的各联合检测方式,首次就其联合诊断方法的诞生及研究进展进行简要综述,进一步明确cfDNA联合液体活检在诊断早期肝癌中的重要意义与潜力,以期为更好地利用肝癌诊断标志物提供探索思路。

     

  • [1] Chinese Society of Hepatology, Chinese Medical Association. Consensus on the secondary prevention for primary liver cancer (2021 edition)[J]. J Clin Hepatol, 2021, 37(3): 532-542. DOI: 10.3969/j.issn.1001-5256.2021.03.008.

    中华医学会肝病学分会. 原发性肝癌二级预防共识(2021年版)[J]. 临床肝胆病杂志, 2021, 37(3): 532-542. DOI: 10.3969/j.issn.1001-5256.2021.03.008.
    [2] LIU J, LIU D, GUO P. Research progress of peripheral blood cfDNA and its methodology in clinical transformation[J]. Chin J Gerontol, 2020, 40(8): 1785-1789. DOI: 10.3969/j.issn.1005- 9202.2020.08.060.

    刘杰, 刘冬, 郭鹏. 外周血cfDNA及其在临床转化中的方法学研究进展[J]. 中国老年学杂志, 2020, 40(8): 1785-1789. DOI: 10.3969/j.issn.1005- 9202.2020.08.060.
    [3] LI GY, LI JY, ZHUANG KM, et al. Progress on circulating tumor DNA in early diagnosis of hepatocellular carcinoma[J/CD]. Chin J Liver Dis (Electronic Version), 2020, 12(3): 6-11. DOI: 10.3969/j.issn.1674-7380.2020.03.002.

    李国印, 李金莹, 庄康敏, 等. 循环肿瘤DNA在肝细胞癌早期诊断中的研究进展[J/CD]. 中国肝脏病杂志(电子版), 2020, 12(3): 6-11. DOI: 10.3969/j.issn.1674-7380.2020.03.002.
    [4] GAI W, SUN K. Epigenetic biomarkers in cell-free DNA and applications in liquid biopsy[J]. Genes (Basel), 2019, 10(1): 32. DOI: 10.3390/genes10010032.
    [5] HOU YJ, ZHANG LQ, FAN HN, et al. Research advances in circulating free DNA in liver cancer and liver-related parasitic diseases[J]. J Clin Hepatol, 2020, 36(2): 430-432. DOI: 10.3969/j.issn.1001-5256.2020.02.043.

    后亚军, 张灵强, 樊海宁. 循环游离DNA在肝癌和肝相关性寄生虫病中的应用进展[J]. 临床肝胆病杂志, 2020, 36(2): 430-432. DOI: 10.3969/j.issn.1001-5256.2020.02.043.
    [6] ZHANG T, YIN M, WANG L, et al. Diagnostic performance of blood-based liquid biopsies in hepatocellular carcinoma: A protocol for systematic review and meta-analysis[J]. Medicine (Baltimore), 2020, 99(41): e22594. DOI: 10.1097/MD.0000000000022594.
    [7] YE Q, LING S, ZHENG S, et al. Liquid biopsy in hepatocellular carcinoma: Circulating tumor cells and circulating tumor DNA[J]. Mol Cancer, 2019, 18(1): 114. DOI: 10.1186/s12943-019-1043-x.
    [8] XU RH, WEI W, KRAWCZYK M, et al. Circulating tumour DNA methylation markers for diagnosis and prognosis of hepatocellular carcinoma[J]. Nat Mater, 2017, 16(11): 1155-1161. DOI: 10.1038/nmat4997.
    [9] 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.
    [10] QIN Z, LJUBIMOV VA, ZHOU C, et al. Cell-free circulating tumor DNA in cancer[J]. Chin J Cancer, 2016, 35(5): 1-9. DOI: 10.1186/s40880-016-0092-4.
    [11] LIAO W, MAO Y, GE P, et al. Value of quantitative and qualitative analyses of circulating cell-free DNA as diagnostic tools for hepatocellular carcinoma: A meta-analysis[J]. Medicine (Baltimore), 2015, 94(14): e722. DOI: 10.1097/MD.0000000000000722.
    [12] WANG T, ZHANG KH, HU PP, et al. Simple and robust diagnosis of early, small and AFP-negative primary hepatic carcinomas: An integrative approach of serum fluorescence and conventional blood tests[J]. Oncotarget, 2016, 7(39): 64053-64070. DOI: 10.18632/oncotarget.11771.
    [13] MAN MR, ZHOU XL, LIU QH. Research progress of primary hepatocellular carcinoma biomarkers[J/CD]. E-J Transl Med, 2018, 5(11): 61-66. DOI: 10.12095/j.issn.2095-6894.2018.11.017.

    满沐苒, 周旭林, 刘清华. 原发性肝癌肿瘤标志物研究进展[J/CD]. 转化医学电子杂志, 2018, 5(11): 61-66. DOI: 10.12095/j.issn.2095-6894.2018.11.017.
    [14] MANDEL P, METAIS P. Nuclear acids In human blood plasma[J]. C R Seances Soc Biol Fil, 1948, 142(3-4): 241-243.
    [15] 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.
    [16] ONO A, FUJIMOTO A, YAMAMOTO Y, et al. Circulating tumor DNA analysis for liver cancers and its usefulness as a liquid biopsy[J]. Cell Mol Gastroenterol Hepatol, 2015, 1(5): 516-534. DOI: 10.1016/j.jcmgh.2015.06.009.
    [17] PENG B, ZENG YL, LI ZY, et al. Technical progress of liquid biopsy in the diagnosis of liver cancer[J]. Chin J Exp Surg, 2020, 37(3): 578-582. DOI: 10.3760/cma.j.issn.1001-9030.2020.03.056.

    彭渤, 曾永联, 李泽远, 等. 液体活检在肝癌诊断方面的技术进展[J]. 中华实验外科杂志, 2020, 37(3): 578-582. DOI: 10.3760/cma.j.issn.1001-9030.2020.03.056.
    [18] LIAO W, MAO Y, GE P, et al. Value of quantitative and qualitative analyses of circulating cell-free DNA as diagnostic tools for hepatocellular carcinoma: A meta-analysis[J]. Medicine (Baltimore), 2015, 94(14): e722. DOI: 10.1097/MD.0000000000000722.
    [19] YAN L, CHEN Y, ZHOU J, et al. Diagnostic value of circulating cell-free DNA levels for hepatocellular carcinoma[J]. Int J Infect Dis, 2018, 67: 92-97. DOI: 10.1016/j.ijid.2017.12.002.
    [20] HUANG A, ZHANG X, ZHOU SL, et al. Plasma circulating cell-free DNA integrity as a promising biomarker for diagnosis and surveillance in patients with hepatocellular carcinoma[J]. J Cancer, 2016, 7(13): 1798-1803. DOI: 10.7150/jca.15618.
    [21] TAO K, BIAN Z, ZHANG Q, et al. Machine learning-based genome-wide interrogation of somatic copy number aberrations in circulating tumor DNA for early detection of hepatocellular carcinoma[J]. EBioMedicine, 2020, 56: 102811. DOI: 10.1016/j.ebiom.2020.102811.
    [22] LIAO W, YANG H, XU H, et al. Noninvasive detection of tumor-associated mutations from circulating cell-free DNA in hepatocellular carcinoma patients by targeted deep sequencing[J]. Oncotarget, 2016, 7(26): 40481-40490. DOI: 10.18632/oncotarget.9629.
    [23] AN Y, GUAN Y, XU Y, et al. The diagnostic and prognostic usage of circulating tumor DNA in operable hepatocellular carcinoma[J]. Am J Transl Res, 2019, 11(10): 6462-6474.
    [24] QU C, WANG Y, WANG P, et al. Detection of early-stage hepatocellular carcinoma in asymptomatic HBsAg-seropositive individuals by liquid biopsy[J]. Proc Natl Acad Sci U S A, 2019, 116(13): 6308-6312. DOI: 10.1073/pnas.1819799116.
    [25] XIONG Y, XIE CR, ZHANG S, et al. Detection of a novel panel of somatic mutations in plasma cell-free DNA and its diagnostic value in hepatocellular carcinoma[J]. Cancer Manag Res, 2019, 11: 5745-5756. DOI: 10.2147/CMAR.S197455.
    [26] CAI J, CHEN L, ZHANG Z, et al. Genome-wide mapping of 5-hydroxymethylcytosines in circulating cell-free DNA as a non-invasive approach for early detection of hepatocellular carcinoma[J]. Gut, 2019, 68(12): 2195-2205. DOI: 10.1136/gutjnl-2019-318882.
    [27] CAI Z, ZHANG J, HE Y, et al. Liquid biopsy by combining 5-hydroxymethylcytosine signatures of plasma cell-free DNA and protein biomarkers for diagnosis and prognosis of hepatocellular carcinoma[J]. ESMO Open, 2021, 6(1): 100021. DOI: 10.1016/j.esmoop.2020.100021.
    [28] LIZUKA N, OKA M, SAKAIDA I, et al. Efficient detection of hepatocellular carcinoma by a hybrid blood test of epigenetic and classical protein markers[J]. Clin Chim Acta, 2011, 412(1-2): 152-158. DOI: 10.1016/j.cca.2010.09.028.
    [29] SUN FK, FAN YC, ZHAO J, et al. Detection of TFPI2 methylation in the serum of hepatocellular carcinoma patients[J]. Dig Dis Sci, 2013, 58(4): 1010-1015. DOI: 10.1007/s10620-012-2462-3.
    [30] LI F, FAN YC, GAO S, et al. Methylation of serum insulin-like growth factor-binding protein 7 promoter in hepatitis B virus-associated hepatocellular carcinoma[J]. Genes Chromosomes Cancer, 2014, 53(1): 90-97. DOI: 10.1002/gcc.22120.
    [31] KUO CC, LIN CY, SHIH YL, et al. Frequent methylation of HOXA9 gene in tumor tissues and plasma samples from human hepatocellular carcinomas[J]. Clin Chem Lab Med, 2014, 52(8): 1235-1245. DOI: 10.1515/cclm-2013-0780.
    [32] JI XF, FAN YC, GAO S, et al. MT1M and MT1G promoter methylation as biomarkers for hepatocellular carcinoma[J]. World J Gastroenterol, 2014, 20(16): 4723-4729. DOI: 10.3748/wjg.v20.i16.4723.
    [33] HAN LY, FAN YC, MU NN, et al. Aberrant DNA methylation of G-protein-coupled bile acid receptor Gpbar1 (TGR5) is a potential biomarker for hepatitis B Virus associated hepatocellular carcinoma[J]. Int J Med Sci, 2014, 11(2): 164-171. DOI: 10.7150/ijms.6745.
    [34] HUANG G, KROCKER JD, KIRK JL, et al. Evaluation of INK4A promoter methylation using pyrosequencing and circulating cell-free DNA from patients with hepatocellular carcinoma[J]. Clin Chem Lab Med, 2014, 52(6): 899-909. DOI: 10.1515/cclm-2013-0885.
    [35] WEN L, LI J, GUO H, et al. Genome-scale detection of hypermethylated CpG islands in circulating cell-free DNA of hepatocellular carcinoma patients[J]. Cell Res, 2015, 25(11): 1250-1264. DOI: 10.1038/cr.2015.126.
    [36] DOU CY, FAN YC, CAO CJ, et al. Sera DNA methylation of CDH1, DNMT3b and ESR1 promoters as biomarker for the early diagnosis of hepatitis B virus-related hepatocellular carcinoma[J]. Dig Dis Sci, 2016, 61(4): 1130-1138. DOI: 10.1007/s10620-015-3975-3.
    [37] LU CY, CHEN SY, PENG HL, et al. Cell-free methylation markers with diagnostic and prognostic potential in hepatocellular carcinoma[J]. Oncotarget, 2017, 8(4): 6406-6418. DOI: 10.18632/oncotarget.14115.
    [38] DONG X, HOU Q, CHEN Y, et al. Diagnostic value of the methylation of multiple gene promoters in serum in hepatitis B virus-related hepatocellular carcinoma[J]. Dis Markers, 2017, 2017: 2929381. DOI: 10.1155/2017/2929381.
    [39] HU N, FAN XP, FAN YC, et al. Hypomethylated ubiquitin-conjugating enzyme2 Q1 (UBE2Q1) gene promoter in the serum is a promising biomarker for hepatitis B virus-associated hepatocellular carcinoma[J]. Tohoku J Exp Med, 2017, 242(2): 93-100. DOI: 10.1620/tjem.242.93.
    [40] KISIEL JB, DUKEK BA, V S R KANIPAKAM R, et al. Hepatocellular carcinoma detection by plasma methylated DNA: Discovery, phase I pilot, and phase Ⅱ clinical validation[J]. Hepatology, 2019, 69(3): 1180-1192. DOI: 10.1002/hep.30244.
    [41] CHALASANI NP, RAMASUBRAMANIAN TS, BHATTACHARYA A, et al. A novel blood-based panel of methylated DNA and protein markers for detection of early-stage hepatocellular carcinoma[J]. Clin Gastroenterol Hepatol, 2021, 19(12): 2597-2605. e4. DOI: 10.1016/j.cgh.2020.08.065.
    [42] ELSEWIFY W, HASSAN EA, MEKKY MA, et al. Usefulness of circulating methylated p16 as a noninvasive molecular biomarker for hepatitis C-related hepatocellular carcinoma with normal serum alpha-fetoprotein levels[J]. Int J Gen Med, 2020, 13: 147-155. DOI: 10.2147/IJGM.S249272.
    [43] COHEN JD, LI L, WANG Y, et al. Detection and localization of surgically resectable cancers with a multi-analyte blood test[J]. Science, 2018, 359(6378): 926-930. DOI: 10.1126/science.aar3247.
    [44] GUO S, DIEP D, PLONGTHONGKUM N, et al. Identification of methylation haplotype blocks aids in deconvolution of heterogeneous tissue samples and tumor tissue-of-origin mapping from plasma DNA[J]. Nat Genet, 2017, 49(4): 635-642. DOI: 10.1038/ng.3805.
    [45] COHEN JD, JAVED AA, THOBURN C, et al. Combined circulating tumor DNA and protein biomarker-based liquid biopsy for the earlier detection of pancreatic cancers[J]. Proc Natl Acad Sci U S A, 2017, 114(38): 10202-10207. DOI: 10.1073/pnas.1704961114.
    [46] WAN L, GUO L, HU Y, et al. Comparing the diagnostic value of serum oligosaccharide chain (G-test) and alpha-fetoprotein for hepatitis B virus-related liver cancer[J]. Clin Biochem, 2021, 89: 44-50. DOI: 10.1016/j.clinbiochem.2020.12.005.
  • 3期单独排(2).pdf
  • 加载中
计量
  • 文章访问数:  530
  • HTML全文浏览量:  136
  • PDF下载量:  123
  • 被引次数: 0
出版历程
  • 收稿日期:  2021-08-12
  • 出版日期:  2022-04-20
  • 分享
  • 用微信扫码二维码

    分享至好友和朋友圈

目录

    /

    返回文章
    返回