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Current Hepatology Reports
Erschienen in: Current Hepatology Reports 4/2020

10.11.2020 | Hepatic Cancer (N Parikh, Section Editor)

Genomic Landscape of HCC

verfasst von: Nia Adeniji, Renumathy Dhanasekaran

Erschienen in: Current Hepatology Reports | Ausgabe 4/2020

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Abstract

Introduction

Hepatocellular carcinoma (HCC) is a leading cause of cancer-related mortality in the world, and it has limited treatment options. Understanding the molecular drivers of HCC is important to develop novel biomarkers and therapeutics.

Purpose of Review

HCC arises in a complex background of chronic hepatitis, fibrosis, and liver regeneration which lead to genomic changes. Here, we summarize studies that have expanded our understanding of the molecular landscape of HCC.

Recent Findings

Recent technological advances in next-generation sequencing (NGS) have elucidated specific genetic and molecular programs involved in hepatocarcinogenesis. We summarize the major somatic mutations and epigenetic changes have been identified in NGS-based studies. We also describe promising molecular therapies and immunotherapies which target specific genetic and epigenetic molecular events.

Summary

The genomic landscape of HCC is incredibly complex and heterogeneous. Promising new developments are helping us decipher the molecular drivers of HCC and leading to new therapies.
Literatur
1.
Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2018;68:394–424.PubMed
2.
Valery PC, Laversanne M, Clark PJ, Petrick JL, McGlynn KA, Bray F. Projections of primary liver cancer to 2030 in 30 countries worldwide. Hepatology. 2018;67:600–11.PubMed
3.
Seegobin K, Majeed U, Ritter A, Wylie N, Starr JS, Jones JC, et al. Factors affecting time to treatment in hepatocellular cancer. J Clin Oncol. 2020;38:e19088.
4.
Huang Y-T, Jen C-L, Yang H-I, Lee M-H, Su J, Lu S-N, et al. Lifetime risk and sex difference of hepatocellular carcinoma among patients with chronic hepatitis B and C. J Clin Oncol. 2011;29:3643–50.PubMedPubMedCentral
5.
Baumert TF, Jühling F, Ono A, Hoshida Y. Hepatitis C-related hepatocellular carcinoma in the era of new generation antivirals. BMC Med. 2017;15:52.PubMedPubMedCentral
6.
Marengo A, Rosso C, Bugianesi E. Liver cancer: connections with obesity, fatty liver, and cirrhosis. Annu Rev Med. 2016;67:103–17.PubMed
7.
Mittal S, El-Serag HB. Epidemiology of hepatocellular carcinoma: consider the population. J Clin Gastroenterol. 2013;47(Suppl):S2–6.PubMedPubMedCentral
8.
Park EJ, Lee JH, Yu G-Y, He G, Ali SR, Holzer RG, et al. Dietary and genetic obesity promote liver inflammation and tumorigenesis by enhancing IL-6 and TNF expression. Cell. 2010;140:197–208.PubMedPubMedCentral
9.
Zámbó V, Simon-Szabó L, Szelényi P, Kereszturi É, Bánhegyi G, Csala M. Lipotoxicity in the liver. World J Hepatol. 2013;5:550.PubMedPubMedCentral
10.
Rowe J, Ghouri Y, Mian I. Review of hepatocellular carcinoma: epidemiology, etiology, and carcinogenesis. Journal of Carcinogenesis. 2017;16:1.PubMedPubMedCentral
11.
Do AL, Wong CR, Nguyen LH, Nguyen VG, Trinh H, Nguyen MH. Hepatocellular carcinoma incidence in noncirrhotic patients with chronic hepatitis B and patients with cirrhosis of all etiologies. J Clin Gastroenterol. 2014;48:644–9.PubMed
12.
Tobari M, Hashimoto E, Taniai M, Kodama K, Kogiso T, Tokushige K, et al. The characteristics and risk factors of hepatocellular carcinoma in nonalcoholic fatty liver disease without cirrhosis. J Gastroenterol Hepatol. 2020;35:862–9.PubMed
13.
Menahem B, Lubrano J, Duvoux C, Mulliri A, Alves A, Costentin C, et al. Liver transplantation versus liver resection for hepatocellular carcinoma in intention to treat: an attempt to perform an ideal meta-analysis. Liver Transpl. 2017;23:836–44.PubMed
14.
Tang W, Chen Z, Zhang W, Cheng Y, Zhang B, Wu F, et al. The mechanisms of sorafenib resistance in hepatocellular carcinoma: theoretical basis and therapeutic aspects. Signal Transduct Target Ther. 2020;5:87.PubMedPubMedCentral
15.
Marisi G, Cucchetti A, Ulivi P, Canale M, Cabibbo G, Solaini L, et al. Ten years of sorafenib in hepatocellular carcinoma: are there any predictive and/or prognostic markers? World J Gastroenterol. 2018;24:4152–63.PubMedPubMedCentral
16.
Krishnamoorthy SK, Relias V, Sebastian S, Jayaraman V, Saif MW. Management of regorafenib-related toxicities: a review. Ther Adv Gastroenterol. 2015;8:285–97.
17.
Xu W, Liu K, Chen M, Sun J-Y, McCaughan GW, Lu X-J, et al. Immunotherapy for hepatocellular carcinoma: recent advances and future perspectives. Ther Adv Med Oncol. 2019;11:1758835919862692.PubMedPubMedCentral
18.
Personeni N, Pressiani T, Rimassa L. Lenvatinib for the treatment of unresectable hepatocellular carcinoma: evidence to date. J Hepatocell Carcinoma. 2019;6:31–9.PubMedPubMedCentral
19.
Zhan P, Ji Y-N. Prognostic significance of TP53 expression for patients with hepatocellular carcinoma: a meta-analysis. Hepatobiliary Surg Nutr. 2014;3:11–7.PubMedPubMedCentral
20.
Ma Z, Guo D, Wang Q, Liu P, Xiao Y, Wu P, et al. Lgr5-mediated p53 repression through PDCD5 leads to doxorubicin resistance in hepatocellular carcinoma. Theranostics. 2019;9:2967–83.PubMedPubMedCentral
21.
22.
Zhu Z-Z, Bao L-L, Zhao K, Xu Q, Zhu JY, Zhu KX, et al. Copy number aberrations of multiple genes identified as prognostic markers for extrahepatic metastasis-free survival of patients with hepatocellular carcinoma. Curr Med Sci. 2019;39:759–65.PubMed
23.
Long J, Wang A, Bai Y, Lin J, Yang X, Wang D, et al. Development and validation of a TP53-associated immune prognostic model for hepatocellular carcinoma. EBioMedicine. 2019;42:363–74.PubMedPubMedCentral
24.
Qu Y-L, Deng C-H, Luo Q, Shang X-Y, Wu J-X, Shi Y, et al. Arid1a regulates insulin sensitivity and lipid metabolism. EBioMedicine. 2019;42:481–93.PubMedPubMedCentral
25.
26.
Huang C-Y, Hsieh F-S, Wang C-Y, Chen LJ, Chang SS, Tsai MH, et al. Palbociclib enhances radiosensitivity of hepatocellular carcinoma and cholangiocarcinoma via inhibiting ataxia telangiectasia–mutated kinase–mediated DNA damage response. Eur J Cancer. 2018;102:10–22.PubMed
27.
Samstein RM, Lee C-H, Shoushtari AN, Hellmann MD, Shen R, Janjigian YY, et al. Tumor mutational load predicts survival after immunotherapy across multiple cancer types. Nat Genet. 2019;51:202–6.PubMedPubMedCentral
28.
Nault J-C, Zucman-Rossi J. TERT promoter mutations in primary liver tumors. Clin Res Hepatol Gastroenterol. 2016;40:9–14.PubMed
29.
Torrecilla S, Sia D, Harrington AN, Zhang Z, Cabellos L, Cornella H, et al. Trunk mutational events present minimal intra- and inter-tumoral heterogeneity in hepatocellular carcinoma. J Hepatol. 2017;67:1222–31.PubMed
30.
Nault JC, Mallet M, Pilati C, Calderaro J, Bioulac-Sage P, Laurent C, et al. High frequency of telomerase reverse-transcriptase promoter somatic mutations in hepatocellular carcinoma and preneoplastic lesions. Nat Commun. 2013;4:2218.PubMedPubMedCentral
31.
Donaires FS, Scatena NF, Alves-Paiva RM, Podlevsky JD, Logeswaran D, Santana BA, et al. Telomere biology and telomerase mutations in cirrhotic patients with hepatocellular carcinoma. PLoS One. 2017;12:e0183287.PubMedPubMedCentral
32.
Pezzuto F, Buonaguro L, Buonaguro FM, Tornesello ML. Frequency and geographic distribution of TERT promoter mutations in primary hepatocellular carcinoma. Infect Agent Cancer. 2017;12:27.PubMedPubMedCentral
33.
Zulehner G, Mikula M, Schneller D, van Zijl F, Huber H, Sieghart W, et al. Nuclear beta-catenin induces an early liver progenitor phenotype in hepatocellular carcinoma and promotes tumor recurrence. Am J Pathol. 2010;176:472–81.PubMedPubMedCentral
34.
Pezzuto F, Izzo F, Buonaguro L, Annunziata C, Tatangelo F, Botti G, et al. Tumor specific mutations in TERT promoter and CTNNB1 gene in hepatitis B and hepatitis C related hepatocellular carcinoma. Oncotarget. 2016;7:54253–62.PubMedPubMedCentral
35.
Khalaf AM, Fuentes D, Morshid AI, Burke MR, Kaseb AO, Hassan M, et al. Role of Wnt/β-catenin signaling in hepatocellular carcinoma, pathogenesis, and clinical significance. Journal of Hepatocellular Carcinoma. 2018;5:61–73.PubMedPubMedCentral
36.
Li P, Cao Y, Li Y, Zhou L, Liu X, Geng M. Expression of Wnt-5a and β-catenin in primary hepatocellular carcinoma. Int J Clin Exp Pathol. 2014;7:3190–5.PubMedPubMedCentral
37.
Ataide EC, Perales SR, Silva MG, Filho FC, Sparapani AC, Latuf Filho PF, et al. Immunoexpression of heat shock protein 70, glypican 3, glutamine synthetase, and beta-catenin in hepatocellular carcinoma after liver transplantation: association between positive glypican 3 and beta-catenin with the presence of larger nodules. Transplant Proc. 2017;49:858–62.PubMed
38.
Vonderheide R, McRee A, Johnson J, Shields A, Bahary N, Chintakuntlawar A. Pharmaceuticals I (2016) hTERT immunotherapy alone or in combination with IL-12 DNA followed by electroporation in 734 adults with solid tumors at high risk of relapse (TRT-001). Identifier NCT02960594. https://​clinicaltrials.​gov/​ct2/​show/​NCT02960594.
39.
Trung NT, Hoan NX, Trung PQ, Binh MT, Van Tong H, Toan NL, et al. Clinical significance of combined circulating TERT promoter mutations and miR-122 expression for screening HBV-related hepatocellular carcinoma. Sci Rep. 2020;10:8181.PubMedPubMedCentral
40.
Waisberg J. Wnt−/−β-catenin pathway signaling in human hepatocellular carcinoma. World J Hepatol. 2015;7:2631.PubMedPubMedCentral
41.
Yuan K, Xie K, Lan T, Xu L, Chen X, Li X, et al. TXNDC12 promotes EMT and metastasis of hepatocellular carcinoma cells via activation of β-catenin. Cell Death Differ. 2020;27:1355–68.PubMed
42.
Cui Y, Wu X, Lin C, Zhang X, Ye L, Ren L, et al. AKIP1 promotes early recurrence of hepatocellular carcinoma through activating the Wnt/β-catenin/CBP signaling pathway. Oncogene. 2019;38:5516–29.PubMed
43.
Hechtman JF, Abou-Alfa GK, Stadler ZK, Mandelker DL, Roehrl MHA, Zehir A, et al. Somatic HNF1A mutations in the malignant transformation of hepatocellular adenomas: a retrospective analysis of data from MSK-IMPACT and TCGA. Hum Pathol. 2019;83:1–6.PubMed
44.
Rebouissou S, Imbeaud S, Balabaud C, Boulanger V, Bertrand-Michel J, Tercé F, et al. HNF1alpha inactivation promotes lipogenesis in human hepatocellular adenoma independently of SREBP-1 and carbohydrate-response element-binding protein (ChREBP) activation. J Biol Chem. 2007;282:14437–46.PubMed
45.
Xiong S, Wang R, Chen Q, Luo J, Wang J, Zhao Z, et al. Cancer-associated fibroblasts promote stem cell-like properties of hepatocellular carcinoma cells through IL-6/STAT3/Notch signaling. Am J Cancer Res. 2018;8:302–16.PubMedPubMedCentral
46.
Bi Y-H, Han W-Q, Li R-F, Wang Y-J, Du Z-S, Wang X-J, et al. Signal transducer and activator of transcription 3 promotes the Warburg effect possibly by inducing pyruvate kinase M2 phosphorylation in liver precancerous lesions. World J Gastroenterol. 2019;25:1936–49.PubMedPubMedCentral
47.
Huang L, Jian Z, Gao Y, Zhou P, Zhang G, Jiang B, et al. RPN2 promotes metastasis of hepatocellular carcinoma cell and inhibits autophagy via STAT3 and NF-κB pathways. Aging. 2019;11:6674–90.PubMedPubMedCentral
48.
Yang L, Zhang X-Y, Li K, Li AP, Yang WD, Yang R, et al. Protopanaxadiol inhibits epithelial-mesenchymal transition of hepatocellular carcinoma by targeting STAT3 pathway. Cell Death Dis. 2019;10:630.PubMedPubMedCentral
49.
Xu G, Zhu L, Wang Y, Shi Y, Gong A, Wu C. Stattic enhances radiosensitivity and reduces radio-induced migration and invasion in HCC cell lines through an apoptosis pathway. Biomed Res Int. 2017;2017:1832494.PubMedPubMedCentral
50.
Yoo C, Kang J, Kim K-P, Lim HY, Kim JH, Lee MA, et al. Phase I dose-finding study of OPB-111077, a novel STAT3 inhibitor, in patients with advanced hepatocellular carcinoma. J Clin Oncol. 2018;36:4078.
51.
Okusaka T, Ueno H, Ikeda M, Mitsunaga S, Ozaka M, Ishii H, et al. Phase 1 and pharmacological trial of OPB-31121, a signal transducer and activator of transcription-3 inhibitor, in patients with advanced hepatocellular carcinoma. Hepatol Res. 2015;45:1283–91.PubMed
52.
Shitara K, Yodo Y, Iino S. A phase I study of Napabucasin plus paclitaxel for Japanese patients with advanced/recurrent gastric cancer. In Vivo. 2019;33:933–7.PubMedPubMedCentral
53.
54.
Cheng J, Wei D, Ji Y, Chen L, Yang L, Li G, et al. Integrative analysis of DNA methylation and gene expression reveals hepatocellular carcinoma-specific diagnostic biomarkers. Genome Med. 2018;10:42.PubMedPubMedCentral
55.
Lee S, Lee HJ, Kim J-H, Lee H-S, Jang JJ, Kang GH. Aberrant CpG island hypermethylation along multistep hepatocarcinogenesis. Am J Pathol. 2003;163:1371–8.PubMedPubMedCentral
56.
Wu X, Yao X, Cao Q, Wu Z, Wang Z, Liu F, et al. Clinicopathological and prognostic significance of CDH1 hypermethylation in hepatocellular carcinoma: a meta-analysis. Cancer Manag Res. 2019;11:857–64.PubMedPubMedCentral
57.
Gailhouste L, Liew LC, Yasukawa K, Hatada I, Tanaka Y, Nakagama H, et al. Differentiation therapy by epigenetic reconditioning exerts antitumor effects on liver cancer cells. Mol Ther. 2018;26:1840–54.PubMedPubMedCentral
58.
Liu J, Liu Y, Meng L, Liu K, Ji B. Targeting the PD-L1/DNMT1 axis in acquired resistance to sorafenib in human hepatocellular carcinoma. Oncol Rep. 2017;38:899–907.PubMedPubMedCentral
59.
Jueliger S, Lyons J, Cannito S, Pata I, Pata P, Shkolnaya M, et al. Efficacy and epigenetic interactions of novel DNA hypomethylating agent guadecitabine (SGI-110) in preclinical models of hepatocellular carcinoma. Epigenetics. 2016;11:709–20.PubMedPubMedCentral
60.
Xu X, Tao Y, Shan L, Chen R, Jiang H, Qian Z, et al. The role of MicroRNAs in hepatocellular carcinoma. J Cancer. 2018;9:3557–69.PubMedPubMedCentral
61.
Chen S-Y, Ma D-N, Chen Q-D, Zhang J-J, Tian Y-R, Wang Z-C, et al. MicroRNA-200a inhibits cell growth and metastasis by targeting Foxa2 in hepatocellular carcinoma. J Cancer. 2017;8:617–25.PubMedPubMedCentral
62.
Moshiri F, Callegari E, D’Abundo L, Corrà F, Lupini L, Sabbioni S, et al. Inhibiting the oncogenic mir-221 by microRNA sponge: toward microRNA-based therapeutics for hepatocellular carcinoma. Gastroenterol Hepatol Bed Bench. 2014;7:43–54.PubMedPubMedCentral
63.
Li S-P, Xu H-X, Yu Y, et al. LncRNA HULC enhances epithelial-mesenchymal transition to promote tumorigenesis and metastasis of hepatocellular carcinoma via the miR-200a-3p/ZEB1 signaling pathway. Oncotarget. 2016;7:42431–46.PubMedPubMedCentral
64.
Fujisaka Y, Iwata T, Tamai K, Nakamura M, Mochizuki M, Shibuya R, et al. Long non-coding RNA HOTAIR up-regulates chemokine (C-C motif) ligand 2 and promotes proliferation of macrophages and myeloid-derived suppressor cells in hepatocellular carcinoma cell lines. Oncol Lett. 2017. https://​doi.​org/​10.​3892/​ol.​2017.​7322.
65.
van der Ree MH, van der Meer AJ, van Nuenen AC, de Bruijne J, Ottosen S, Janssen HL, et al. Miravirsen dosing in chronic hepatitis C patients results in decreased microRNA-122 levels without affecting other microRNAs in plasma. Aliment Pharmacol Ther. 2016;43:102–13.PubMed
66.
Voi M, Fu S, Nemunaitis J, Bauman J, Bessudo A, Hamid O, et al. 590 final results of a phase Ib study of CUDC-101, a multitargeted inhibitor of EGFR, HER2, and HDAC, in patients with advanced head and neck, gastric, breast, liver, and non-small cell lung cancer. Eur J Cancer. 2012;48:181.
67.
Yeo W, Chung HC, Chan SL, Wang LZ, Lim R, Picus J, et al. Epigenetic therapy using belinostat for patients with unresectable hepatocellular carcinoma: a multicenter phase I/II study with biomarker and pharmacokinetic analysis of tumors from patients in the Mayo phase II consortium and the Cancer Therapeutics Research Group. J Clin Oncol. 2012;30:3361–7.PubMedPubMedCentral
68.
Mani SKK, Zhang H, Diab A, Pascuzzi PE, Lefrançois L, Fares N, et al. EpCAM-regulated intramembrane proteolysis induces a cancer stem cell-like gene signature in hepatitis B virus-infected hepatocytes. J Hepatol. 2016;65:888–98.PubMedPubMedCentral
69.
Chao J, Zhao S, Sun H. Dedifferentiation of hepatocellular carcinoma: molecular mechanisms and therapeutic implications. Am J Transl Res. 2020;12:2099–109.PubMedPubMedCentral
70.
Muramatsu S, Tanaka S, Mogushi K, Adikrisna R, Aihara A, Ban D, et al. Visualization of stem cell features in human hepatocellular carcinoma reveals in vivo significance of tumor-host interaction and clinical course. Hepatology. 2013;58:218–28.PubMed
71.
Ye C, Zhang X, Chen X, Cao Q, Zhang X, Zhou Y, et al. Multiple novel hepatocellular carcinoma signature genes are commonly controlled by the master pluripotency factor OCT4. Cell Oncol. 2020;43:279–95.
72.
Zhang B-H, Yang J, Jiang L, Lyu T, Kong LX, Tan YF, et al. Development and validation of a 14-gene signature for prognosis prediction in hepatocellular carcinoma. Genomics. 2020;112:2763–71.PubMed
73.
Zhang J, Baddoo M, Han C, Strong MJ, Cvitanovic J, Moroz K, et al. Gene network analysis reveals a novel 22-gene signature of carbon metabolism in hepatocellular carcinoma. Oncotarget. 2016;7:49232–45.PubMedPubMedCentral
74.
Li N, Zhao L, Guo C, Liu C, Liu Y. Identification of a novel DNA repair-related prognostic signature predicting survival of patients with hepatocellular carcinoma. Cancer Manag Res. 2019;11:7473–84.PubMedPubMedCentral
75.
Chan L-K, Ng IO-L. Proteomic profiling in liver cancer: another new page. Transl Gastroenterol Hepatol. 2019;4:47.PubMedPubMedCentral
76.
He Y, Luo Y, Zhang D, Wang X, Zhang P, Li H, et al. PGK1-mediated cancer progression and drug resistance. Am J Cancer Res. 2019;9:2280–302.PubMedPubMedCentral
77.
Zhao Y, Li Y, Liu W, Xing S, Wang D, Chen J, et al. Identification of noninvasive diagnostic biomarkers for hepatocellular carcinoma by urinary proteomics. J Proteome. 2020;225:103780.
78.
Blokzijl F, de Ligt J, Jager M, Sasselli V, Roerink S, Sasaki N, et al. Tissue-specific mutation accumulation in human adult stem cells during life. Nature. 2016;538:260–4.PubMedPubMedCentral
79.
Brunner SF, Roberts ND, Wylie LA, Moore L, Aitken SJ, Davies SE, et al. Somatic mutations and clonal dynamics in healthy and cirrhotic human liver. Nature. 2019;574:538–42.PubMedPubMedCentral
80.
Brazhnik K, Sun S, Alani O, Kinkhabwala M, Wolkoff AW, Maslov AY, et al. Single-cell analysis reveals different age-related somatic mutation profiles between stem and differentiated cells in human liver. Sci Adv. 2020;6:eaax2659.PubMedPubMedCentral
81.
Yu L-X, Ling Y, Wang H-Y. Role of nonresolving inflammation in hepatocellular carcinoma development and progression. NPJ Precis Oncol. 2018;2:6.PubMedPubMedCentral
82.
Zhang B-L, Ji X, Yu L-X, et al. Somatic mutation profiling of liver and biliary cancer by targeted next generation sequencing. Oncol Lett. 2018;16:6003–12.PubMedPubMedCentral
83.
Bouaoun L, Sonkin D, Ardin M, Hollstein M, Byrnes G, Zavadil J, et al. TP53 variations in human cancers: new lessons from the IARC TP53 database and genomics data. Hum Mutat. 2016;37:865–76.PubMed
84.
Teramoto T, Satonaka K, Kitazawa S, Fujimori T, Hayashi K, Maeda S. Gene abnormalities are closely related to hepatoviral infections and occur at a late stage of hepatocarcinogenesis. Cancer Res. 1994;54:53.
85.
Zhang W, He H, Zang M, et al. Genetic features of aflatoxin-associated hepatocellular carcinoma. Gastroenterology. 2017;153:249–262.e2.PubMed
86.
Chittmittrapap S, Chieochansin T, Chaiteerakij R, Treeprasertsuk S, Klaikaew N, Tangkijvanich P, et al. Prevalence of aflatoxin induced p53 mutation at codon 249 (R249s) in hepatocellular carcinoma patients with and without hepatitis B surface antigen (HBsAg). Asian Pac J Cancer Prev. 2013;14:7675–9.PubMed
87.
Villanueva A, Hoshida Y. Depicting the role of TP53 in hepatocellular carcinoma progression. J Hepatol. 2011;55:724–5.PubMed
88.
Liu Y, Yan J, Wang F. Effects of TACE combined with precise RT on p53 gene expression and prognosis of HCC patients. Oncol Lett. 2018;16:5733–8.PubMedPubMedCentral
89.
Nahon P, Nault J-C. Constitutional and functional genetics of human alcohol-related hepatocellular carcinoma. Liver Int. 2017;37:1591–601.PubMed
90.
Sung W-K, Zheng H, Li S, Chen R, Liu X, Li Y, et al. Genome-wide survey of recurrent HBV integration in hepatocellular carcinoma. Nat Genet. 2012;44:765–9.PubMed
91.
Moore A, Wu L, Chuang J-C, Sun X, Luo X, Gopal P, et al. Arid1a loss drives nonalcoholic steatohepatitis in mice through epigenetic dysregulation of hepatic lipogenesis and fatty acid oxidation. Hepatology. 2019;69:1931–45.PubMedPubMedCentral
92.
Vasileiou G, Ekici AB, Uebe S, Zweier C, Hoyer J, Engels H, et al. Chromatin-remodeling-factor ARID1B represses Wnt/β-catenin signaling. Am J Hum Genet. 2015;97:445–56.PubMedPubMedCentral
93.
94.
Peng Y, Gao B, Zhou Z, Chen T, Xie W, Huang M, et al. Hepatocellular carcinoma with ARID1A mutation is associated with higher TMB and poor survival. J Clin Oncol. 2020;38:e16667.
95.
Hu C, Li W, Tian F, Jiang K, Liu X, Cen J, et al. Arid1a regulates response to anti-angiogenic therapy in advanced hepatocellular carcinoma. J Hepatol. 2018;68:465–75.PubMed
96.
Yu JI, Choi C, Ha SY, Park CK, Kang SY, Joh JW, et al. Clinical importance of TERT overexpression in hepatocellular carcinoma treated with curative surgical resection in HBV endemic area. Sci Rep. 2017;7:12258.PubMedPubMedCentral
97.
Cheng Y, Huang M, Xie W, Gao C, Cai S, Ji J, et al. Chromosome 8q24 amplification predicts prognosis for patients with advanced hepatocellular carcinoma (HCC). J Clin Oncol. 2019;37:e15654.
98.
Li X, Xu W, Kang W, Wong SH, Wang M, Zhou Y, et al. Genomic analysis of liver cancer unveils novel driver genes and distinct prognostic features. Theranostics. 2018;8:1740–51.PubMedPubMedCentral
99.
Jiao J, Watt GP, Stevenson HL, Calderone TL, Fisher-Hoch SP, Ye Y, et al. Telomerase reverse transcriptase mutations in plasma DNA in patients with hepatocellular carcinoma or cirrhosis: prevalence and risk factors. Hepatology Communications. 2018;2:718–31.PubMedPubMedCentral
100.
101.
Chen J, Rajasekaran M, Xia H, Zhang X, Kong SN, Sekar K, et al. The microtubule-associated protein PRC1 promotes early recurrence of hepatocellular carcinoma in association with the Wnt/β-catenin signalling pathway. Gut. 2016;65:1522–34.PubMedPubMedCentral
102.
Caruso S, Calderaro J, Letouzé E, Nault JC, Couchy G, Boulai A, et al. Germline and somatic DICER1 mutations in familial and sporadic liver tumors. J Hepatol. 2017;66:734–42.PubMed
103.
104.
Cancer Genome Atlas Research Network. Electronic address: wheeler@bcm.edu, Cancer Genome Atlas Research Network. Comprehensive and integrative genomic characterization of hepatocellular carcinoma. Cell. 2017;169:1327–1341.e23.
105.
Calderaro J, Couchy G, Imbeaud S, Amaddeo G, Letouzé E, Blanc JF, et al. Histological subtypes of hepatocellular carcinoma are related to gene mutations and molecular tumour classification. J Hepatol. 2017;67:727–38.PubMed
106.
Doycheva I, Thuluvath PJ. Systemic therapy for advanced hepatocellular carcinoma: an update of a rapidly evolving field. J Clin Exp Hepatol. 2019;9:588–96.PubMedPubMedCentral
107.
Zheng A, Chevalier N, Calderoni M, Dubuis G, Dormond O, Ziros PG, et al. CRISPR/Cas9 genome-wide screening identifies KEAP1 as a sorafenib, lenvatinib, and regorafenib sensitivity gene in hepatocellular carcinoma. Oncotarget. 2019;10:7058–70.PubMedPubMedCentral
108.
Reznik Y, Dao T, Coutant R, Chiche L, Jeannot E, Clauin S, et al. Hepatocyte nuclear factor-1 alpha gene inactivation: cosegregation between liver adenomatosis and diabetes phenotypes in two maturity-onset diabetes of the young (MODY)3 families. J Clin Endocrinol Metab. 2004;89:1476–80.PubMed
109.
Zeng X, Lin Y, Yin C, Zhang X, Ning BF, Zhang Q, et al. Recombinant adenovirus carrying the hepatocyte nuclear factor-1alpha gene inhibits hepatocellular carcinoma xenograft growth in mice. Hepatology. 2011;54:2036–47.PubMed
110.
Takashima Y, Horisawa K, Udono M, Ohkawa Y, Suzuki A. Prolonged inhibition of hepatocellular carcinoma cell proliferation by combinatorial expression of defined transcription factors. Cancer Sci. 2018;109:3543–53.PubMedPubMedCentral
111.
Kan Z, Zheng H, Liu X, Li S, Barber TD, Gong Z, et al. Whole-genome sequencing identifies recurrent mutations in hepatocellular carcinoma. Genome Res. 2013;23:1422–33.PubMedPubMedCentral
112.
Yin Z, Ma T, Lin Y, Lu X, Zhang C, Chen S, et al. IL-6/STAT3 pathway intermediates M1/M2 macrophage polarization during the development of hepatocellular carcinoma. J Cell Biochem. 2018;119:9419–32.PubMed
113.
Ki Kim S, Ueda Y, Hatano E, Kakiuchi N, Takeda H, Goto T, et al. TERT promoter mutations and chromosome 8p loss are characteristic of nonalcoholic fatty liver disease-related hepatocellular carcinoma. Int J Cancer. 2016;139:2512–8.PubMed
114.
Zhou C, Zhang W, Chen W, Yin Y, Atyah M, Liu S, et al. Integrated analysis of copy number variations and gene expression profiling in hepatocellular carcinoma. Sci Rep. 2017;7:10570.PubMedPubMedCentral
115.
Schlaeger C, Longerich T, Schiller C, et al. Etiology-dependent molecular mechanisms in human hepatocarcinogenesis. Hepatology. 2008;47:511–20.PubMed
116.
Ao L, Song X, Li X, Tong M, Guo Y, Li J, et al. An individualized prognostic signature and multi-omics distinction for early stage hepatocellular carcinoma patients with surgical resection. Oncotarget. 2016;7:24097–110.PubMedPubMedCentral
117.
Yu M-C, Lee C-W, Lee Y-S, Lian J-H, Tsai C-L, Liu Y-P, et al. Prediction of early-stage hepatocellular carcinoma using OncoScan chromosomal copy number aberration data. World J Gastroenterol. 2017;23:7818–29.PubMedPubMedCentral
118.
Pedica F, Ruzzenente A, Bagante F, Capelli P, Cataldo I, Pedron S, et al. A re-emerging marker for prognosis in hepatocellular carcinoma: the add-value of fishing c-myc gene for early relapse. PLoS One. 2013;8:e68203.PubMedPubMedCentral
119.
Kent LN, Bae S, Tsai S-Y, Tang X, Srivastava A, Koivisto C, et al. Dosage-dependent copy number gains in E2f1 and E2f3 drive hepatocellular carcinoma. J Clin Invest. 2017;127:830–42.PubMedPubMedCentral
120.
Yu X, Huang J, Wu S, Huang Y, Shan Y, Lu C. Copy number variations of MMP-9 are prognostic biomarkers for hepatocellular carcinoma. Transl Cancer Res. 2020;9:698–706.
121.
Kawai-Kitahata F, Asahina Y, Tanaka S, Kakinuma S, Murakawa M, Nitta S, et al. Comprehensive analyses of mutations and hepatitis B virus integration in hepatocellular carcinoma with clinicopathological features. J Gastroenterol. 2016;51:473–86.PubMed
122.
Sun S, Li Y, Han S, Jia H, Li X, Li X. A comprehensive genome-wide profiling comparison between HBV and HCV infected hepatocellular carcinoma. BMC Med Genet. 2019;12:147.
123.
Zhang B, Deng C, Wang L, Zhou F, Zhang S, Kang W, et al. Upregulation of UBE2Q1 via gene copy number gain in hepatocellular carcinoma promotes cancer progression through β-catenin-EGFR-PI3K-Akt-mTOR signaling pathway. Mol Carcinog. 2018;57:201–15.PubMed
124.
Dong S, Wu Y, Yu S, Yang Y, Lu L, Fan S. Increased EXT1 gene copy number correlates with increased mRNA level predicts short disease-free survival in hepatocellular carcinoma without vascular invasion. Medicine. 2018;97:e12625.PubMedPubMedCentral
125.
Zhou S-L, Zhou Z-J, Hu Z-Q, Song CL, Luo YJ, Luo CB, et al. Genomic sequencing identifies WNK2 as a driver in hepatocellular carcinoma and a risk factor for early recurrence. J Hepatol. 2019;71:1152–63.PubMed
126.
Kaibori M, Sakai K, Ishizaki M, Matsushima H, de Velasco MA, Matsui K, et al. Increased FGF19 copy number is frequently detected in hepatocellular carcinoma with a complete response after sorafenib treatment. Oncotarget. 2016;7:49091–8.PubMedPubMedCentral
127.
Shen J, Wang S, Zhang Y-J, Kappil M, Wu HC, Kibriya MG, et al. Genome-wide DNA methylation profiles in hepatocellular carcinoma. Hepatology. 2012;55:1799–808.PubMedPubMedCentral
128.
Gentilini D, Scala S, Gaudenzi G, Garagnani P, Capri M, Cescon M, et al. Epigenome-wide association study in hepatocellular carcinoma: identification of stochastic epigenetic mutations through an innovative statistical approach. Oncotarget. 2017;8:41890–902.PubMedPubMedCentral
129.
Yang Z, Zhou L, Wu L-M, Lai M-C, Xie H-Y, Zhang F, et al. Overexpression of long non-coding RNA HOTAIR predicts tumor recurrence in hepatocellular carcinoma patients following liver transplantation. Ann Surg Oncol. 2011;18:1243–50.PubMed
130.
Lu X-F, Cao X-Y, Zhu Y-J, Wu ZR, Zhuang X, Shao MY, et al. Histone deacetylase 3 promotes liver regeneration and liver cancer cells proliferation through signal transducer and activator of transcription 3 signaling pathway. Cell Death Dis. 2018;9:398.PubMedPubMedCentral
131.
Ji H, Zhou Y, Zhuang X, Zhu Y, Wu Z, Lu Y, et al. HDAC3 deficiency promotes liver cancer through a defect in H3K9ac/H3K9me3 transition. Cancer Res. 2019;79:3676–88.PubMedPubMedCentral
132.
Yang Y, Zhang J, Wu T, Xu X, Cao G, Li H, et al. Histone deacetylase 2 regulates the doxorubicin (Dox) resistance of hepatocarcinoma cells and transcription of ABCB1. Life Sci. 2019;216:200–6.PubMed
133.
Gahr S, Mayr C, Kiesslich T, et al. The pan-deacetylase inhibitor panobinostat affects angiogenesis in hepatocellular carcinoma models via modulation of CTGF expression. Int J Oncol. 2015;47:963–70.PubMed
134.
Bitzer M, Horger M, Giannini EG, Ganten TM, Wörns MA, Siveke JT, et al. Resminostat plus sorafenib as second-line therapy of advanced hepatocellular carcinoma - the SHELTER study. J Hepatol. 2016;65:280–8.PubMed
135.
Lee J-S, Chu I-S, Heo J, Calvisi DF, Sun Z, Roskams T, et al. Classification and prediction of survival in hepatocellular carcinoma by gene expression profiling. Hepatology. 2004;40:667–76.PubMed
136.
Segal E, Friedman N, Koller D, Regev A. A module map showing conditional activity of expression modules in cancer. Nat Genet. 2004;36:1090–8.PubMed
137.
Yamashita T, Ji J, Budhu A, Forgues M, Yang W, Wang H–Y, et al. EpCAM-positive hepatocellular carcinoma cells are tumor-initiating cells with stem/progenitor cell features. Gastroenterology. 2009;136:1012–24.PubMed
138.
Li Y, Farmer RW, Yang Y, Martin RCG. Epithelial cell adhesion molecule in human hepatocellular carcinoma cell lines: a target of chemoresistence. BMC Cancer. 2016;16:228.PubMedPubMedCentral
139.
Jiang Y, Sun A, Zhao Y, et al. Proteomics identifies new therapeutic targets of early-stage hepatocellular carcinoma. Nature. 2019;567:257–61.PubMed
140.
Gao Q, Zhu H, Dong L, Shi W, Chen R, Song Z, et al. Integrated proteogenomic characterization of HBV-related hepatocellular carcinoma. Cell. 2019;179(2):561–77.
141.
Liu H, Chen H, Wu X, Sun Y, Wang Y, Zeng Y, et al. The serum proteomics tracking of hepatocellular carcinoma early recurrence following radical resection. Cancer Manag Res. 2019;11:2935–46.PubMedPubMedCentral
Metadaten
Titel
Genomic Landscape of HCC
verfasst von
Nia Adeniji
Renumathy Dhanasekaran
Publikationsdatum
10.11.2020
Verlag
Springer US
Erschienen in
Current Hepatology Reports / Ausgabe 4/2020
Elektronische ISSN: 2195-9595
DOI
https://doi.org/10.1007/s11901-020-00553-7

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