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LU Hui, XIE Zhengyuan. Research Progress in Noninvasive Early Diagnosis of Hepatocellular Carcinoma[J]. Cancer Research on Prevention and Treatment, 2023, 50(1): 75-80. DOI: 10.3971/j.issn.1000-8578.2023.22.0642
Citation: LU Hui, XIE Zhengyuan. Research Progress in Noninvasive Early Diagnosis of Hepatocellular Carcinoma[J]. Cancer Research on Prevention and Treatment, 2023, 50(1): 75-80. DOI: 10.3971/j.issn.1000-8578.2023.22.0642
shu

Research Progress in Noninvasive Early Diagnosis of Hepatocellular Carcinoma

  • 1.

    Medical College of Nanchang University, Nanchang 330006, China

  • 2.

    Department of Gastroenterology, The Second Affiliated Hospital of Nanchang University, Nanchang 330006, China

Funding: 

National Natural Science Foundation of China 81860119

Key Project of Natural Science Foundation of Jiangxi Province 20212ACB206017

Key Science and Technology R & D Project of Jiangxi Province 20203BBG73044

Science and Technology Research Project of Education Department of Jiangxi Province GJJ200193

More Information
  • Corresponding author:

    XIE Zhengyuan, E-mail: xzyxzy1230@163.com

  • Received Date: June 09, 2022
  • Revised Date: July 20, 2022
  • Available Online: January 12, 2024
    Graphical Abstract
    • Abstract

  • Liver cancer is a common tumor that seriously threatens human life and health. Given that the early onset of liver cancer is insidious and lacks specific symptoms, hence it is difficult to screen through routine examination. Thus, clinical diagnosis of liver cancer is mostly in the advanced stage. However, advanced liver cancer has few treatment options, poor prognosis and high relapse rate, thereby causing a high mortality rate. Therefore, early diagnosis of liver cancer is particularly important. Currently, non-invasive screening of liver cancer widely used in clinical setups lacks sufficient sensitivity and specificity, hence, a more reliable diagnostic method needs to be found urgently. This article reviews the research progress of noninvasive early diagnosis of liver cancer to provide a reference for raising the early diagnosis rate of liver cancer.

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  • Competing interests: The authors declare that they have no competing interests.

    • References (56)
  • [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]
    刘宗超, 李哲轩, 张阳, 等. 2020全球癌症统计报告解读[J]. 肿瘤综合治疗电子杂志, 2021, 7(2): 1-14. https://www.cnki.com.cn/Article/CJFDTOTAL-ZLZD202102001.htm

    Liu ZC, Li ZX, Zhang Y, et al. Interpretation on the report of global cancer statistics 2020[J]. Zhong Liu Zong He Zhi Liao Dian Zi Za Zhi, 2021, 7(2): 1-14. https://www.cnki.com.cn/Article/CJFDTOTAL-ZLZD202102001.htm
    [3]
    Tsuchiya N, Sawada Y, Endo I, et al. Biomarkers for the early diagnosis of hepatocellular carcinoma[J]. World J Gastroenterol, 2015, 21(37): 10573-10583. doi: 10.3748/wjg.v21.i37.10573
    [4]
    曹毛毛, 李贺, 孙殿钦, 等. 全球肝癌2020年流行病学现状[J]. 中华肿瘤防治杂志, 2022, 29(5): 322-328. https://www.cnki.com.cn/Article/CJFDTOTAL-QLZL202205003.htm

    Cao MM, Li H, Sun DQ, et al. Global epidemiology of liver cancer in 2020[J]. Zhonghua Zhong Liu Fang Zhi Za Zhi, 2022, 29(5): 322-328. https://www.cnki.com.cn/Article/CJFDTOTAL-QLZL202205003.htm
    [5]
    Song P, Gao J, Inagaki Y, et al. Biomarkers: evaluation of screening for and early diagnosis of hepatocellular carcinoma in Japan and China[J]. Liver Cancer, 2013, 2(1): 31-39. doi: 10.1159/000346220
    [6]
    Jiang HY, Chen J, Xia CC, et al. Noninvasive imaging of hepatocellular carcinoma: From diagnosis to prognosis[J]. World J Gastroenterology, 2018, 24(22): 2348-2362. doi: 10.3748/wjg.v24.i22.2348
    [7]
    陆荫英, 赵海涛, 程家敏, 等. 肝胆肿瘤分子诊断临床应用专家共识[J]. 肝癌电子杂志, 2020, 36(7): 1482-1488. https://www.cnki.com.cn/Article/CJFDTOTAL-GADZ202001004.htm

    Lu YY, Zhao HT, Cheng JM, et al. Consensus for clinical application of molecular diagnosis on hepatobiliary carcinoma[J]. Gan Ai Dian Zi Za Zhi, 2020, 36(7): 1482-1488. https://www.cnki.com.cn/Article/CJFDTOTAL-GADZ202001004.htm
    [8]
    高春芳, 房萌, 季君. 多学科甲胎蛋白异质体临床应用专家共识[J]. 诊断学理论与实践, 2018, 17(1): 19-24. https://www.cnki.com.cn/Article/CJFDTOTAL-ZDLS201801004.htm

    Gao CF, Fang M, Ji J. Expert consensus on the clinical application of multidisciplinary alpha fetoprotein heterogene[J]. Zhen Duan Xue Li Lun Yu Shi Jian, 2018, 17(1): 19-24. https://www.cnki.com.cn/Article/CJFDTOTAL-ZDLS201801004.htm
    [9]
    Zhou JM, Wang T, Zhang KH. AFP-L3 for the diagnosis of early hepatocellular carcinoma: A meta-analysis[J]. Medicine (Baltimore), 2021, 100(43): e27673. doi: 10.1097/MD.0000000000027673
    [10]
    周何琪, 任志刚, 余祖江. 血清PIVKA-Ⅱ及AFP-L3(%)在AFP低水平肝癌中的诊断价值[J]. 河南医学研究, 2019, 28(14): 2521-2523. doi: 10.3969/j.issn.1004-437X.2019.14.007

    Zhou HQ, Ren ZG, Yu ZJ. Clinical value of combined detection of serum PIVKA-Ⅱ and AFP-L3(%) in the diagnosis of primary carcinoma of liver with low concentration of AFP[J]. He'nan Yi Xue Yan Jiu, 2019, 28(14): 2521-2523. doi: 10.3969/j.issn.1004-437X.2019.14.007
    [11]
    Yang Y, Li G, Lu Z, et al. Progression of Prothrombin Induced by Vitamin K Absence-Ⅱ in Hepatocellular Carcinoma[J]. Front Oncol, 2021, 11: 726213. doi: 10.3389/fonc.2021.726213
    [12]
    Svobodova S, Karlikova M, Topolcan O, et al. PIVKA-Ⅱ as a Potential New Biomarker for Hepatocellular Carcinoma-A Pilot Study[J]. In Vivo, 2018, 32(6): 1551-1554. doi: 10.21873/invivo.11413
    [13]
    Zhang SG, Huang Y. Usefulness of AFP, PIVKA-Ⅱ, and Their Combination in Diagnosing Hepatocellular Carcinoma Based on Upconversion Luminescence Immunochromatography[J]. Lab Med, 2022, 53(5): 488-494. doi: 10.1093/labmed/lmac027
    [14]
    Best J, Bechmann LP, Sowa JP, et al. GALAD Score Detects Early Hepatocellular Carcinoma in an International Cohort of Patients With Nonalcoholic Steatohepatitis[J]. Clin Gastroenterol Hepatol, 2020, 18(3): 728-735.e4. doi: 10.1016/j.cgh.2019.11.012
    [15]
    Schotten C, Ostertag B, Sowa JP, et al. GALAD Score Detects Early-Stage Hepatocellular Carcinoma in a European Cohort of Chronic Hepatitis B and C Patients[J]. Pharmaceuticals (Basel), 2021, 14(8): 735. doi: 10.3390/ph14080735
    [16]
    Singal AG, Tayob N, Mehta A, et al. GALAD demonstrates high sensitivity for HCC surveillance in a cohort of patients with cirrhosis[J]. Hepatology, 2022, 75(3): 541-549. doi: 10.1002/hep.32185
    [17]
    Kolluri A, Ho M. The Role of Glypican-3 in Regulating Wnt, YAP, and Hedgehog in Liver Cancer[J]. Front Oncol, 2019, 9: 708. doi: 10.3389/fonc.2019.00708
    [18]
    Xu D, Su C, Sun L, et al. Performance of Serum Glypican 3 in Diagnosis of Hepatocellular Carcinoma: A meta-analysis[J]. Ann Hepatol, 2019, 18(1): 58-67. doi: 10.5604/01.3001.0012.7863
    [19]
    Zhou F, Shang W, Yu X, et al. Glypican-3: A promising biomarker for hepatocellular carcinoma diagnosis and treatment[J]. Med Res Rev, 2018, 38(2): 741-767. doi: 10.1002/med.21455
    [20]
    Xing H, Qiu H, Ding X, et al. Clinical performance of α-L-fucosidase for early detection of hepatocellular carcinoma[J]. Biomark Med, 2019, 13(7): 545-555. doi: 10.2217/bmm-2018-0414
    [21]
    Liu D, Luo Y, Chen L, et al. Diagnostic value of 5 serum biomarkers for hepatocellular carcinoma with different epidemiological backgrounds: A large-scale, retrospective study[J]. Cancer Biol Med, 2021, 18(1): 256-270. doi: 10.20892/j.issn.2095-3941.2020.0207
    [22]
    Ratnasari N, Lestari P, Renovaldi D, et al. Potential plasma biomarkers: miRNA-29c, miRNA-21, and miRNA-155 in clinical progression of Hepatocellular Carcinoma patients[J]. PLoS One, 2022, 17(2): e0263298. doi: 10.1371/journal.pone.0263298
    [23]
    Wang Y, Zhang C, Zhang P, et al. Serum exosomal microRNAs combined with alpha-fetoprotein as diagnostic markers of hepatocellular carcinoma[J]. Cancer Med, 2018, 7(5): 1670-1679. doi: 10.1002/cam4.1390
    [24]
    吕金明, 李燕, 苏凤君. miRNA-122联合肿瘤标志物在慢性乙肝病毒感染肝硬化及早期肝癌诊断中的价值[J]. 中华医院感染学杂志, 2020, 30(19): 2922-2926. https://www.cnki.com.cn/Article/CJFDTOTAL-ZHYY202019012.htm

    Lyu JM, Li Y, Su FJ. Diagnostic value of miRNA-122 combined with tumor markers in cirrhosis and early liver cancer of patients with chronic hepatitis B virus infection[J]. Zhonghua Yi Yuan Gan Ran Xue Za Zhi, 2020, 30(19): 2922-2926. https://www.cnki.com.cn/Article/CJFDTOTAL-ZHYY202019012.htm
    [25]
    Zhou J, Yu L, Gao X, et al. Plasma microRNA panel to diagnose hepatitis B virus-related hepatocellular carcinoma[J]. J Clin Oncol, 2011, 29(36): 4781-4788. doi: 10.1200/JCO.2011.38.2697
    [26]
    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(2022年版)[J]. 肿瘤防治研究, 2022, 49(3): 251-276. doi: 10.3971/j.issn.1000-8578.2022.03.0001

    National Health Commission of the People's Republic of China. Standard for diagnosis and treatment of primary Hepetic Carcinorma (2022 edition)[J]. Zhong Liu Fang Zhi Yan Jiu, 2022, 49(3): 251-276. doi: 10.3971/j.issn.1000-8578.2022.03.0001
    [27]
    Fiala C, Kulasingam V, Diamandis EP. Circulating Tumor DNA for Early Cancer Detection[J]. J Appl Lab Med, 2018, 3(2): 300-313. doi: 10.1373/jalm.2018.026393
    [28]
    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
    [29]
    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
    [30]
    Huang Z, Hua D, Hu Y, et al. Quantitation of plasma circulating DNA using quantitative PCR for the detection of hepatocellular carcinoma[J]. Pathol Oncol Res, 2012, 18(2): 271-276. doi: 10.1007/s12253-011-9438-z
    [31]
    Yang YJ, Chen H, Huang P, et al. Quantification of plasma hTERT DNA in hepatocellular carcinoma patients by quantitative fluorescent polymerase chain reaction[J]. Clin Invest Med, 2011, 34(4): E238. doi: 10.25011/cim.v34i4.15366
    [32]
    Zhang C, Li J, Huang T, et al. Meta-analysis of DNA methylation biomarkers in hepatocellular carcinoma[J]. Oncotarget, 2016, 7(49): 81255-81267. doi: 10.18632/oncotarget.13221
    [33]
    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
    [34]
    Liao WJ, Yang HY, Xu HF, 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
    [35]
    Ng CKY, 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.
    [36]
    Icer MA, Gezmen-Karadag M. The multiple functions and mechanisms of osteopontin[J]. Clin Biochem, 2018, 59: 17-24. doi: 10.1016/j.clinbiochem.2018.07.003
    [37]
    Abdel-Hafiz SM, Hamdy HEM, Khorshed FM, et al. Evaluation of Osteopontin as a Biomarker in Hepatocellular Carcinomas in Egyptian Patients with Chronic HCV Cirrhosis[J]. Asian Pac J Cancer Prev, 2018, 19(4): 1021-1027.
    [38]
    Sun T, Tang Y, Sun D, et al. Osteopontin versus alpha-fetoprotein as a diagnostic marker for hepatocellular carcinoma: a meta-analysis[J]. Onco Targets Ther, 2018, 11: 8925-8935. doi: 10.2147/OTT.S186230
    [39]
    张洪川, 张玉玺, 段丛迪. 骨桥蛋白和Ezrin蛋白在原发性肝癌组织中的表达及其与临床特征和预后的相关性[J]. 肝脏, 2019, 24(5): 549-552. doi: 10.3969/j.issn.1008-1704.2019.05.023

    Zhang HC, Zhang YX, Duan CD. Expression of osteoqiao protein and Ezrin protein in primary hepatocellular carcinoma tissue and their correlation with clinical characteristics and prognosis[J]. Gan Zang, 2019, 24(5): 549-552. doi: 10.3969/j.issn.1008-1704.2019.05.023
    [40]
    Distefano JK, Davis B. Diagnostic and Prognostic Potential of AKR1B10 in Human Hepatocellular Carcinoma[J]. Cancers (Basel), 2019, 11(4): 486. doi: 10.3390/cancers11040486
    [41]
    Ye X, Li C, Zu X, et al. A Large-Scale Multicenter Study Validates Aldo-Keto Reductase Family 1 Member B10 as a Prevalent Serum Marker for Detection of Hepatocellular Carcinoma[J]. Hepatology, 2019, 69(6): 2489-2501.
    [42]
    Murata A, Genda T, Ichida T, et al. Pretreatment AKR1B10 expression predicts the risk of hepatocellular carcinoma development after hepatitis C virus eradication[J]. World J Gastroenterol, 2016, 22(33): 7569-7578. doi: 10.3748/wjg.v22.i33.7569
    [43]
    Torzilli G, Minagawa M, Takayama T, et al. Accurate preoperative evaluation of liver mass lesions without fine-needle biopsy[J]. Hepatology, 1999, 30(4): 889-893. doi: 10.1002/hep.510300411
    [44]
    Cruite I, Tang A, Sirlin CB. Imaging-based diagnostic systems for hepatocellular carcinoma[J]. AJR Am J Roentgenol, 2013, 201(1): 41-55. doi: 10.2214/AJR.13.10570
    [45]
    Kim TH, Yoon JH, Lee JM. Emerging Role of Hepatobiliary Magnetic Resonance Contrast Media and Contrast-Enhanced Ultrasound for Noninvasive Diagnosis of Hepatocellular Carcinoma: Emphasis on Recent Updates in Major Guidelines[J]. Korean J Radiol, 2019, 20(6): 863-879. doi: 10.3348/kjr.2018.0450
    [46]
    Kogita S, Imai Y, Okada M, et al. Gd-EOB-DTPA-enhanced magnetic resonance images of hepatocellular carcinoma: correlation with histological grading and portal blood flow[J]. Eur Radiol, 2010, 20(10): 2405-2413. doi: 10.1007/s00330-010-1812-9
    [47]
    Zhou J, Sun H, Wang Z, et al. Guidelines for the Diagnosis and Treatment of Hepatocellular Carcinoma (2019 Edition)[J]. Liver Cancer, 2020, 9(6): 682-720. doi: 10.1159/000509424
    [48]
    Aubé C, Oberti F, Lonjon J, et al. EASL and AASLD recommendations for the diagnosis of HCC to the test of daily practice[J]. Liver Int, 2017, 37(10): 1515-1525. doi: 10.1111/liv.13429
    [49]
    Wilson SR, Lyshchik A, Piscaglia F, et al. CEUS LI-RADS: algorithm, implementation, and key differences from CT/MRI[J]. Abdom Radiol (NY), 2018, 43(1): 127-142. doi: 10.1007/s00261-017-1250-0
    [50]
    Makoyeva A, Kim TK, Jang H-J, et al. Use of CEUS LI-RADS for the Accurate Diagnosis of Nodules in Patients at Risk for Hepatocellular Carcinoma: A Validation Study[J]. Radiol Imaging Cancer, 2020, 2(2): e190014. doi: 10.1148/rycan.2020190014
    [51]
    Schwabe RF, Greten TF. Gut microbiome in HCC-Mechanisms, diagnosis and therapy[J]. J Hepatol, 2020, 72(2): 230-238. doi: 10.1016/j.jhep.2019.08.016
    [52]
    Xie G, Wang X, Huang F, et al. Dysregulated hepatic bile acids collaboratively promote liver carcinogenesis[J]. Int J Cancer, 2016, 139(8): 1764-1775. doi: 10.1002/ijc.30219
    [53]
    Li K, Liu J, Qin X. Research progress of gut microbiota in hepatocellular carcinoma[J]. J Clin Lab Anal, 2022, 36(7): e24512. https://www.researchgate.net/publication/361418719_Research_progress_of_gut_microbiota_in_hepatocellular_carcinoma/fulltext/62d5202466bd1654d66ee992/Research-progress-of-gut-microbiota-in-hepatocellular-carcinoma.pdf?_sg%5B0%5D=started_experiment_milestone&_rtd=e30%3D
    [54]
    Ponziani FR, Bhoori S, Castelli C, et al. Hepatocellular Carcinoma Is Associated With Gut Microbiota Profile and Inflammation in Nonalcoholic Fatty Liver Disease[J]. Hepatology, 2019, 69(1): 107-120. doi: 10.1002/hep.30036
    [55]
    Ren Z, Li A, Jiang J, et al. Gut microbiome analysis as a tool towards targeted non-invasive biomarkers for early hepatocellular carcinoma[J]. Gut, 2019, 68(6): 1014-1023. https://gut.bmj.com/content/gutjnl/early/2018/07/25/gutjnl-2017-315084.full.pdf
    [56]
    丁惠国, 屠红, 曲春枫, 等. 原发性肝癌的分层筛查与监测指南(2020版)[J]. 临床肝胆病杂志, 2021, 37(2): 286-295. https://www.cnki.com.cn/Article/CJFDTOTAL-LCGD202102013.htm

    Ding HG, Tu H, Qu CF, et al. Guidelines for stratified screening and surveillance of primary liver cancer (2020 edition)[J]. Lin Chuang Gan Dan Bing Za Zhi, 2021, 37(2): 286-295. https://www.cnki.com.cn/Article/CJFDTOTAL-LCGD202102013.htm
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