中文English
ISSN 1001-5256
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

肝细胞癌分子异质性与临床精准治疗

邹强 王军 文良志 王斌 张毅

邹强,王军,文良志,等. 肝细胞癌分子异质性与临床精准治疗[J]. 临床肝胆病杂志, 2021, 37(8): 1765-1769. DOI: 10.3969/j.issn.1001-5256.2021.08.006
引用本文: 邹强,王军,文良志,等. 肝细胞癌分子异质性与临床精准治疗[J]. 临床肝胆病杂志, 2021, 37(8): 1765-1769. DOI: 10.3969/j.issn.1001-5256.2021.08.006
ZOU Q, WANG J, WEN LZ, et al. Molecular heterogeneity of hepatocellular carcinoma and its precise treatment in clinical practice [J]. J Clin Hepatol, 2021, 37(8): 1765-1769. DOI: 10.3969/j.issn.1001-5256.2021.08.006
Citation: ZOU Q, WANG J, WEN LZ, et al. Molecular heterogeneity of hepatocellular carcinoma and its precise treatment in clinical practice [J]. J Clin Hepatol, 2021, 37(8): 1765-1769. DOI: 10.3969/j.issn.1001-5256.2021.08.006

肝细胞癌分子异质性与临床精准治疗

DOI: 10.3969/j.issn.1001-5256.2021.08.006
基金项目: 

国家自然科学基金项目 81872027

国家自然科学基金项目 82002585

陆军军医大学科研项目 2019XQY19

详细信息
    通讯作者:

    王斌,wb_tmmu@126.com

    张毅,zhangyi9611@sina.com

  • 中图分类号: R735.7

Molecular heterogeneity of hepatocellular carcinoma and its precise treatment in clinical practice

Funds: 

National Natural Science Foundation of China 81872027

National Natural Science Foundation of China 82002585

Scientific Research Project of Army Medical University 2019XQY19

  • 摘要: 肝细胞癌是我国最常见的肝癌类型,分子异质性显著,极大地制约了临床疗效,因此深入探索其异质性的分子分型,对于制订个体化诊疗策略极为重要。近年来多种高通量测序技术层出不穷,结合多组学特征提出了多种分子分型系统,使临床研究者对肝癌分子异质性有了更加深刻的认识。详细总结了肝细胞癌的分子分型,探讨其与临床病理特征的密切联系,分析分子靶向治疗和免疫治疗的干预新靶标,提出了肝癌精准诊断和个体化治疗的新思路。

     

  • 图  1  2004—2020年间基于基因组、转录组、蛋白质组、代谢特征和免疫特征研究发表的HCC分子亚型

  • [1] CRAIG AJ, VON FELDEN J, GARCIA-LEZANA T, et al. Tumour evolution in hepatocellular carcinoma[J]. Nat Rev Gastroenterol Hepatol, 2020, 17(3): 139-152. DOI: 10.1038/s41575-019-0229-4.
    [2] BRAY F, FERLAY J, SOERJOMATARAM I, et al. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries[J]. CA Cancer J Clin, 2018, 68(6): 394-424. DOI: 10.3322/caac.21492.
    [3] BRUIX J, REIG M, SHERMAN M. Evidence-based diagnosis, staging, and treatment of patients with hepatocellular carcinoma[J]. Gastroenterology, 2016, 150(4): 835-853. DOI: 10.1053/j.gastro.2015.12.041.
    [4] WU Y, LIU Z, XU X. Molecular subtyping of hepatocellular carcinoma: A step toward precision medicine[J]. Cancer Commun (Lond), 2020, 40(12): 681-693. DOI: 10.1002/cac2.12115.
    [5] GONG J, CHEHRAZI-RAFFLE A, REDDI S, et al. Development of PD-1 and PD-L1 inhibitors as a form of cancer immunotherapy: A comprehensive review of registration trials and future considerations[J]. J Immunother Cancer, 2018, 6(1): 8. DOI: 10.1186/s40425-018-0316-z.
    [6] LLOVET JM, ZUCMAN-ROSSI J, PIKARSKY E, et al. Hepatocellular carcinoma[J]. Nat Rev Dis Primers, 2016, 2: 16018. DOI: 10.1038/nrdp.2016.18.
    [7] LLOVET JM, BRU' C, BRUIX J. Prognosis of hepatocellular carcinoma: The BCLC staging classification[J]. Semin Liver Dis, 1999, 19(3): 329-338. DOI: 10.1055/s-2007-1007122.
    [8] BANNASCH P, RIBBACK S, SU Q, et al. Clear cell hepatocellular carcinoma: Origin, metabolic traits and fate of glycogenotic clear and ground glass cells[J]. Hepatobiliary Pancreat Dis Int, 2017, 16(6): 570-594. DOI: 10.1016/S1499-3872(17)60071-7.
    [9] FAIVRE S, RIMASSA L, FINN RS. Molecular therapies for HCC: Looking outside the box[J]. J Hepatol, 2020, 72(2): 342-352. DOI: 10.1016/j.jhep.2019.09.010.
    [10] ERSTAD DJ, FUCHS BC, TANABE KK. Molecular signatures in hepatocellular carcinoma: A step toward rationally designed cancer therapy[J]. Cancer, 2018, 124(15): 3084-3104. DOI: 10.1002/cncr.31257.
    [11] CHIANG DY, VILLANUEVA A, HOSHIDA Y, et al. Focal gains of VEGFA and molecular classification of hepatocellular carcinoma[J]. Cancer Res, 2008, 68(16): 6779-6788. DOI: 10.1158/0008-5472.CAN-08-0742.
    [12] SCHULZE K, IMBEAUD S, LETOUZÉ E, et al. Exome sequencing of hepatocellular carcinomas identifies new mutational signatures and potential therapeutic targets[J]. Nat Genet, 2015, 47(5): 505-511. DOI: 10.1038/ng.3252.
    [13] FUJIMOTO A, FURUTA M, TOTOKI Y, et al. Whole-genome mutational landscape and characterization of noncoding and structural mutations in liver cancer[J]. Nat Genet, 2016, 48(5): 500-509. DOI: 10.1038/ng.3547.
    [14] LEE JS, CHU JS, CHU IS, HEO J, et al. Classification and prediction of survival in hepatocellular carcinoma by gene expression profiling[J]. Hepatology, 2004, 40(3): 667-676. DOI: 10.1002/hep.20375.
    [15] JIANG X, KIM HE, SHU H, et al. Distinctive roles of PHAP proteins and prothymosin-alpha in a death regulatory pathway[J]. Science, 2003, 299(5604): 223-226. DOI: 10.1126/science.1076807.
    [16] SEMENZA GL. Targeting HIF-1 for cancer therapy[J]. Nat Rev Cancer, 2003, 3(10): 721-732. DOI: 10.1038/nrc1187.
    [17] LEE JS, HEO J, LIBBRECHT L, et al. A novel prognostic subtype of human hepatocellular carcinoma derived from hepatic progenitor cells[J]. Nat Med, 2006, 12(4): 410-416. DOI: 10.1038/nm1377.
    [18] BOYAULT S, RICKMAN DS, de REYNIÈS A, et al. Transcriptome classification of HCC is related to gene alterations and to new therapeutic targets[J]. Hepatology, 2007, 45(1): 42-52. DOI: 10.1002/hep.21467.
    [19] HOSHIDA Y, NIJMAN SM, KOBAYASHI M, et al. Integrative transcriptome analysis reveals common molecular subclasses of human hepatocellular carcinoma[J]. Cancer Res, 2009, 69(18): 7385-7392. DOI: 10.1158/0008-5472.CAN-09-1089.
    [20] ZAVADIL J, BÖTTINGER EP. TGF-beta and epithelial-to-mesenchymal transitions[J]. Oncogene, 2005, 24(37): 5764-5774. DOI: 10.1038/sj.onc.1208927.
    [21] GIANNELLI G, BERGAMINI C, FRANSVEA E, et al. Laminin-5 with transforming growth factor-beta1 induces epithelial to mesenchymal transition in hepatocellular carcinoma[J]. Gastroenterology, 2005, 129(5): 1375-1383. DOI: 10.1053/j.gastro.2005.09.055.
    [22] HOPPLER S, KAVANAGH CL. Wnt signalling: Variety at the core[J]. J Cell Sci, 2007, 120(Pt 3): 385-393. DOI: 10.1242/jcs.03363.
    [23] MUTO Y, MORIWAKI H, SHIRATORI Y. Prevention of second primary tumors by an acyclic retinoid, polyprenoic acid, in patients with hepatocellular carcinoma[J]. Digestion, 1998, 59(Suppl 2): 89-91. DOI: 10.1159/000051435.
    [24] ZHANG Y, WANG G, MA W, et al. CdS p-n heterojunction co-boosting with Co(3)O(4) and Ni-MOF-74 for photocatalytic hydrogen evolution[J]. Dalton Trans, 2018, 47(32): 11176-11189. DOI: 10.1039/c8dt02294a.
    [25] HANAHAN D, WEINBERG RA. Hallmarks of cancer: The next generation[J]. Cell, 2011, 144(5): 646-674. DOI: 10.1016/j.cell.2011.02.013.
    [26] DÉSERT R, ROHART F, CANAL F, et al. Human hepatocellular carcinomas with a periportal phenotype have the lowest potential for early recurrence after curative resection[J]. Hepatology, 2017, 66(5): 1502-1518. DOI: 10.1002/hep.29254.
    [27] YANG C, HUANG X, LIU Z, et al. Metabolism-associated molecular classification of hepatocellular carcinoma[J]. Mol Oncol, 2020, 14(4): 896-913. DOI: 10.1002/1878-0261.12639.
    [28] SHANKARAIAH RC, CALLEGARI E, GUERRIERO P, et al. Metformin prevents liver tumourigenesis by attenuating fibrosis in a transgenic mouse model of hepatocellular carcinoma[J]. Oncogene, 2019, 38(45): 7035-7045. DOI: 10.1038/s41388-019-0942-z.
    [29] DUFFY AG, ULAHANNAN SV, MAKOROVA-RUSHER O, et al. Tremelimumab in combination with ablation in patients with advanced hepatocellular carcinoma[J]. J Hepatol, 2017, 66(3): 545-551. DOI: 10.1016/j.jhep.2016.10.029.
    [30] EL-KHOUEIRY AB, SANGRO B, YAU T, et al. Nivolumab in patients with advanced hepatocellular carcinoma (CheckMate 040): An open-label, non-comparative, phase 1/2 dose escalation and expansion trial[J]. Lancet, 2017, 389(10088): 2492-2502. DOI: 10.1016/S0140-6736(17)31046-2.
    [31] KILLOCK D. Immunotherapy: Nivolumab keeps HCC in check and opens avenues for checkmate[J]. Nat Rev Clin Oncol, 2017, 14(7): 392. DOI: 10.1038/nrclinonc.2017.70.
    [32] JIANG Y, SUN A, ZHAO Y, et al. Proteomics identifies new therapeutic targets of early-stage hepatocellular carcinoma[J]. Nature, 2019, 567(7747): 257-261. DOI: 10.1038/s41586-019-0987-8.
    [33] GAO Q, ZHU H, DONG L, et al. Integrated proteogenomic characterization of HBV-related hepatocellular carcinoma[J]. Cell, 2019, 179(2): 561-577. e22. DOI: 10.1016/j.cell.2019.08.052.
    [34] SIA D, JIAO Y, MARTINEZ-QUETGLAS I, et al. Identification of an immune-specific class of hepatocellular carcinoma, based on molecular features[J]. Gastroenterology, 2017, 153(3): 812-826. DOI: 10.1053/j.gastro.2017.06.007.
    [35] KUREBAYASHI Y, OJIMA H, TSUJIKAWA H, et al. Landscape of immune microenvironment in hepatocellular carcinoma and its additional impact on histological and molecular classification[J]. Hepatology, 2018, 68(3): 1025-1041. DOI: 10.1002/hep.29904.
    [36] KIM HD, SONG GW, PARK S, et al. Association between expression level of PD1 by tumor-infiltrating CD8+T cells and features of hepatocellular carcinoma[J]. Gastroenterology, 2018, 155(6): 1936-1950. e17. DOI: 10.1053/j.gastro.2018.08.030.
    [37] ZHANG Q, LOU Y, YANG J, et al. Integrated multiomic analysis reveals comprehensive tumour heterogeneity and novel immunophenotypic classification in hepatocellular carcinomas[J]. Gut, 2019, 68(11): 2019-2031. DOI: 10.1136/gutjnl-2019-318912.
    [38] LIM HY, HEO J, CHOI HJ, et al. A phase Ⅱ study of the efficacy and safety of the combination therapy of the MEK inhibitor refametinib (BAY 86-9766) plus sorafenib for Asian patients with unresectable hepatocellular carcinoma[J]. Clin Cancer Res, 2014, 20(23): 5976-5985. DOI: 10.1158/1078-0432.CCR-13-3445.
    [39] HO DWH, CHAN LK, CHIU YT, et al. TSC1/2 mutations define a molecular subset of HCC with aggressive behaviour and treatment implication[J]. Gut, 2017, 66(8): 1496-1506. DOI: 10.1136/gutjnl-2016-312734.
    [40] SUN W, LI SC, XU L, et al. High FLT3 levels may predict sorafenib benefit in hepatocellular carcinoma[J]. Clin Cancer Res, 2020, 26(16): 4302-4312. DOI: 10.1158/1078-0432.CCR-19-1858.
  • 加载中
图(1)
计量
  • 文章访问数:  137
  • HTML全文浏览量:  43
  • PDF下载量:  67
  • 被引次数: 0
出版历程
  • 收稿日期:  2021-05-28
  • 修回日期:  2021-05-28
  • 刊出日期:  2021-08-16
  • 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