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Current Cancer Drug Targets

Editor-in-Chief

ISSN (Print): 1568-0096
ISSN (Online): 1873-5576

Research Article

Identification of Drug Targets and Agents Associated with Hepatocellular Carcinoma through Integrated Bioinformatics Analysis

Author(s): Md. Alim Hossen, Md. Selim Reza, Md. Harun-Or-Roshid, Md. Ariful Islam, Mst. Ayesha Siddika and Md. Nurul Haque Mollah*

Volume 23, Issue 7, 2023

Published on: 21 March, 2023

Page: [547 - 563] Pages: 17

DOI: 10.2174/1568009623666230214100159

Price: $65

Abstract

Background: Hepatocellular carcinoma (HCC) is the third leading cause of cancer-related death globally. The mechanisms underlying the development of HCC are mostly unknown till now.

Objective: The main goal of this study was to identify potential drug target proteins and agents for the treatment of HCC.

Methods: The publicly available three independent mRNA expression profile datasets were downloaded from the NCBI-GEO database to explore common differentially expressed genes (cDEGs) between HCC and control samples using the Statistical LIMMA approach. Hub-cDEGs as drug targets highlighting their functions, pathways, and regulators were identified by using integrated bioinformatics tools and databases. Finally, Hub-cDEGs-guided top-ranked drug agents were identified by molecular docking study for HCC.

Results: We identified 160 common DEGs (cDEGs) from three independent mRNA expression datasets in which ten cDEGs (CDKN3, TK1, NCAPG, CDCA5, RACGAP1, AURKA, PRC1, UBE2T, MELK, and ASPM) were selected as Hub-cDEGs. The GO functional and KEGG pathway enrichment analysis of Hub-cDEGs revealed some crucial cancer-stimulating biological processes, molecular functions, cellular components, and signaling pathways. The interaction network analysis identified three TF proteins and five miRNAs as the key transcriptional and post-transcriptional regulators of HubcDEGs. Then, we detected the proposed Hub-cDEGs guided top-ranked three anti-HCC drug molecules (Dactinomycin, Vincristine, Sirolimus) that were also highly supported by the already published top-ranked HCC-causing Hub-DEGs mediated receptors.

Conclusion: The findings of this study would be useful resources for diagnosis, prognosis, and therapies of HCC.

Keywords: Hepatocellular carcinoma, differentially expressed genes (DEGs), hub-degs, drug targets, drug agents, integrated bioinformatics approaches.

Graphical Abstract
[1]
Bray, F.; Ferlay, J.; Soerjomataram, I.; Siegel, R.L.; Torre, L.A.; 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(6), 394-424.
[http://dx.doi.org/10.3322/caac.21492] [PMID: 30207593]
[2]
Popper, H.; Shafritz, D.A.; Hoofnagle, J.H. Relation of the hepatitis B virus carrier state to hepatocellular carcinoma. Hepatology, 1987, 7(4), 764-772.
[http://dx.doi.org/10.1002/hep.1840070425] [PMID: 3038725]
[3]
Tanaka, M.; Katayama, F.; Kato, H.; Tanaka, H.; Wang, J.; Qiao, Y.L.; Inoue, M. Hepatitis B and C virus infection and hepatocellular carcinoma in China: a review of epidemiology and control measures. J. Epidemiol., 2011, 21(6), 401-416.
[http://dx.doi.org/10.2188/jea.JE20100190] [PMID: 22041528]
[4]
Wu, J.; Yang, S.; Xu, K.; Ding, C.; Zhou, Y.; Fu, X.; Li, Y.; Deng, M.; Wang, C.; Liu, X.; Li, L. Patterns and trends of liver cancer incidence rates in eastern and southeastern asian countries (1983–2007) and predictions to 2030. Gastroenterology, 2018, 154(6), 1719-1728.e5.
[http://dx.doi.org/10.1053/j.gastro.2018.01.033] [PMID: 29549041]
[5]
Turdean, S.; Gurzu, S.; Turcu, M.; Voidazan, S.; Sin, A. Current data in clinicopathological characteristics of primary hepatic tumors. Rom. J. Morphol. Embryol., 2012, 53(Suppl. 3), 719-724.
[PMID: 23188430]
[6]
Reig, M.; da Fonseca, L.G.; Faivre, S. New trials and results in systemic treatment of HCC. J. Hepatol., 2018, 69(2), 525-533.
[http://dx.doi.org/10.1016/j.jhep.2018.03.028] [PMID: 29653122]
[7]
Cauchy, F.; Zalinski, S.; Dokmak, S.; Fuks, D.; Farges, O.; Castera, L.; Paradis, V.; Belghiti, J. Surgical treatment of hepatocellular carcinoma associated with the metabolic syndrome. Br. J. Surg., 2012, 100(1), 113-121.
[http://dx.doi.org/10.1002/bjs.8963] [PMID: 23147992]
[8]
Luo, J.J.; Zhang, Z.H.; Liu, Q.X.; Zhang, W.; Wang, J.H.; Yan, Z.P. Endovascular brachytherapy combined with stent placement and TACE for treatment of HCC with main portal vein tumor thrombus. Hepatol. Int., 2016, 10(1), 185-195.
[http://dx.doi.org/10.1007/s12072-015-9663-8] [PMID: 26341514]
[9]
Liu, C.Y.; Chen, K.F.; Chen, P.J. Treatment of Liver Cancer. Cold Spring Harb. Perspect. Med., 2015, 5(9), a021535.
[http://dx.doi.org/10.1101/cshperspect.a021535] [PMID: 26187874]
[10]
Faivre, S.; Rimassa, L.; Finn, R.S. Molecular therapies for HCC: Looking outside the box. J. Hepatol., 2020, 72(2), 342-352.
[http://dx.doi.org/10.1016/j.jhep.2019.09.010] [PMID: 31954496]
[11]
Ko, K-L.; Mak, L-Y.; Cheung, K-S.; Yuen, M-F. Hepatocellular carcinoma: recent advances and emerging medical therapies. F1000 Res., 2020, 9, 620.
[http://dx.doi.org/10.12688/f1000research.24543.1]
[12]
Kudo, M.; Finn, R.S.; Qin, S.; Han, K.H.; Ikeda, K.; Piscaglia, F.; Baron, A.; Park, J.W.; Han, G.; Jassem, J.; Blanc, J.F.; Vogel, A.; Komov, D.; Evans, T.R.J.; Lopez, C.; Dutcus, C.; Guo, M.; Saito, K.; Kraljevic, S.; Tamai, T.; Ren, M.; Cheng, A.L. Lenvatinib versus sorafenib in first-line treatment of patients with unresectable hepatocellular carcinoma: a randomised phase 3 non-inferiority trial. Lancet, 2018, 391(10126), 1163-1173.
[http://dx.doi.org/10.1016/S0140-6736(18)30207-1] [PMID: 29433850]
[13]
Bruix, J.; Qin, S.; Merle, P.; Granito, A.; Huang, Y.H.; Bodoky, G.; Pracht, M.; Yokosuka, O.; Rosmorduc, O.; Breder, V.; Gerolami, R.; Masi, G.; Ross, P.J.; Song, T.; Bronowicki, J.P.; Ollivier-Hourmand, I.; Kudo, M.; Cheng, A.L.; Llovet, J.M.; Finn, R.S.; LeBerre, M.A.; Baumhauer, A.; Meinhardt, G.; Han, G. Regorafenib for patients with hepatocellular carcinoma who progressed on sorafenib treatment (RESORCE): A randomised, double-blind, placebo-controlled, phase 3 trial. Lancet, 2017, 389(10064), 56-66.
[http://dx.doi.org/10.1016/S0140-6736(16)32453-9] [PMID: 27932229]
[14]
Abou-Alfa, G.K.; Meyer, T.; Cheng, A.L.; El-Khoueiry, A.B.; Rimassa, L.; Ryoo, B.Y.; Cicin, I.; Merle, P.; Chen, Y.; Park, J.W.; Blanc, J.F.; Bolondi, L.; Klümpen, H.J.; Chan, S.L.; Zagonel, V.; Pressiani, T.; Ryu, M.H.; Venook, A.P.; Hessel, C.; Borgman-Hagey, A.E.; Schwab, G.; Kelley, R.K. Cabozantinib in patients with advanced and progressing hepatocellular carcinoma. N. Engl. J. Med., 2018, 379(1), 54-63.
[http://dx.doi.org/10.1056/NEJMoa1717002] [PMID: 29972759]
[15]
Zhu, A.X.; Kang, Y.K.; Yen, C.J.; Finn, R.S.; Galle, P.R.; Llovet, J.M.; Assenat, E.; Brandi, G.; Pracht, M.; Lim, H.Y.; Rau, K.M.; Motomura, K.; Ohno, I.; Merle, P.; Daniele, B.; Shin, D.B.; Gerken, G.; Borg, C.; Hiriart, J.B.; Okusaka, T.; Morimoto, M.; Hsu, Y.; Abada, P.B.; Kudo, M. 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. Lancet Oncol., 2019, 20(2), 282-296.
[http://dx.doi.org/10.1016/S1470-2045(18)30937-9] [PMID: 30665869]
[16]
Finn, R.S.; Ryoo, B.Y.; Merle, P.; Kudo, M.; Bouattour, M.; Lim, H.Y.; Breder, V.; Edeline, J.; Chao, Y.; Ogasawara, S.; Yau, T.; Garrido, M.; Chan, S.L.; Knox, J.; Daniele, B.; Ebbinghaus, S.W.; Chen, E.; Siegel, A.B.; Zhu, A.X.; Cheng, A.L. Pembrolizumab as second-line therapy in patients with advanced hepatocellular carcinoma in KEYNOTE-240: A randomized, double-blind, phase III trial. J. Clin. Oncol., 2020, 38(3), 193-202.
[http://dx.doi.org/10.1200/JCO.19.01307] [PMID: 31790344]
[17]
El-Khoueiry, A.B.; Sangro, B.; Yau, T.; Crocenzi, T.S.; Kudo, M.; Hsu, C.; Kim, T.Y.; Choo, S.P.; Trojan, J.; Welling, T.H., III; Meyer, T.; Kang, Y.K.; Yeo, W.; Chopra, A.; Anderson, J.; dela Cruz, C.; Lang, L.; Neely, J.; Tang, H.; Dastani, H.B.; Melero, I. Nivolumab in patients with advanced hepatocellular carcinoma (CheckMate 040): an open-label, non-comparative, phase 1/2 dose escalation and expansion trial. Lancet, 2017, 389(10088), 2492-2502.
[http://dx.doi.org/10.1016/S0140-6736(17)31046-2] [PMID: 28434648]
[18]
Finn, R.S.; Qin, S.; Ikeda, M.; Galle, P.R.; Ducreux, M.; Kim, T.Y.; Kudo, M.; Breder, V.; Merle, P.; Kaseb, A.O.; Li, D.; Verret, W.; Xu, D.Z.; Hernandez, S.; Liu, J.; Huang, C.; Mulla, S.; Wang, Y.; Lim, H.Y.; Zhu, A.X.; Cheng, A.L. Atezolizumab plus bevacizumab in unresectable hepatocellular carcinoma. N. Engl. J. Med., 2020, 382(20), 1894-1905.
[http://dx.doi.org/10.1056/NEJMoa1915745] [PMID: 32402160]
[19]
Rudrapal, M.; Khairnar, J. Drug repurposing (DR): An emerging approach in drug discovery. In: Drug Repurposing; IntechOpen, 2020.
[http://dx.doi.org/10.5772/intechopen.93193]
[20]
Chong, C.R.; Sullivan, D.J., Jr New uses for old drugs. Nature, 2007, 448(7154), 645-646.
[http://dx.doi.org/10.1038/448645a] [PMID: 17687303]
[21]
Xue, H.; Li, J.; Xie, H.; Wang, Y. Review of drug repositioning approaches and resources. Int. J. Biol. Sci., 2018, 14(10), 1232-1244.
[http://dx.doi.org/10.7150/ijbs.24612] [PMID: 30123072]
[22]
Mosharaf, M.P.; Reza, M.S.; Kibria, M.K.; Ahmed, F.F.; Kabir, M.H.; Hasan, S.; Mollah, M.N.H. Computational identification of host genomic biomarkers highlighting their functions, pathways and regulators that influence SARS-CoV-2 infections and drug repurposing. Sci. Rep., 2022, 12(1), 4279.
[http://dx.doi.org/10.1038/s41598-022-08073-8] [PMID: 35277538]
[23]
Selim Reza, M.; Harun-Or-Roshid, M.; Ariful Islam, M.; Alim Hossen, M.; Tofazzal Hossain, M.; Feng, S.; Xi, W.; Nurul Haque Mollah, M.; Wei, Y. Bioinformatics screening of potential biomarkers from mRNA expression profiles to discover drug targets and agents for cervical cancer. Int. J. Mol. Sci., 2022, 23(7), 3968.
[http://dx.doi.org/10.3390/ijms23073968]
[24]
Ahmed, F.F.; Reza, M.S.; Sarker, M.S.; Islam, M.S.; Mosharaf, M.P.; Hasan, S.; Mollah, M.N.H. Identification of host transcriptome-guided repurposable drugs for SARS-CoV-1 infections and their validation with SARS-CoV-2 infections by using the integrated bioinformatics approaches. PLoS One, 2022, 17(4), e0266124.
[http://dx.doi.org/10.1371/journal.pone.0266124] [PMID: 35390032]
[25]
Chen, X.; Xia, Z.; Wan, Y.; Huang, P. Identification of hub genes and candidate drugs in hepatocellular carcinoma by integrated bioinformatics analysis. Medicine (Baltimore), 2021, 100(39), e27117.
[http://dx.doi.org/10.1097/MD.0000000000027117] [PMID: 34596112]
[26]
Alam, M.S.; Rahaman, M.M.; Sultana, A.; Wang, G.; Mollah, M.N.H. Statistics and network-based approaches to identify molecular mechanisms that drive the progression of breast cancer. Comput. Biol. Med., 2022, 145, 105508.
[http://dx.doi.org/10.1016/j.compbiomed.2022.105508] [PMID: 35447458]
[27]
Reza, M.S.; Hossen, M.A.; Harun-Or-Roshid, M.; Siddika, M.A.; Kabir, M.H.; Mollah, M.N.H. Metadata analysis to explore hub of the hub-genes highlighting their functions, pathways and regulators for cervical cancer diagnosis and therapies. Discover Oncol., 2022, 13(1), 79.
[http://dx.doi.org/10.1007/s12672-022-00546-6] [PMID: 35994213]
[28]
Woo, H.G.; Choi, J.H.; Yoon, S.; Jee, B.A.; Cho, E.J.; Lee, J.H.; Yu, S.J.; Yoon, J.H.; Yi, N.J.; Lee, K.W.; Suh, K.S.; Kim, Y.J. Integrative analysis of genomic and epigenomic regulation of the transcriptome in liver cancer. Nat. Commun., 2017, 8(1), 839.
[http://dx.doi.org/10.1038/s41467-017-00991-w] [PMID: 29018224]
[29]
Barrett, T.; Wilhite, S.E.; Ledoux, P.; Evangelista, C.; Kim, I.F.; Tomashevsky, M.; Marshall, K.A.; Phillippy, K.H.; Sherman, P.M.; Holko, M.; Yefanov, A.; Lee, H.; Zhang, N.; Robertson, C.L.; Serova, N.; Davis, S.; Soboleva, A. NCBI GEO: archive for functional genomics data sets--update. Nucleic Acids Res., 2013, 41, D991-D995.
[PMID: 23193258]
[30]
Benjamini, Y.; Hochberg, Y. Controlling the false discovery rate: a practical and powerful approach to multiple testing. J. R. Stat. Soc. B, 1995, 57(1), 289-300.
[http://dx.doi.org/10.1111/j.2517-6161.1995.tb02031.x]
[31]
Szklarczyk, D.; Morris, J.H.; Cook, H.; Kuhn, M.; Wyder, S.; Simonovic, M.; Santos, A.; Doncheva, N.T.; Roth, A.; Bork, P.; Jensen, L.J.; von Mering, C. The STRING database in 2017: quality-controlled protein–protein association networks, made broadly accessible. Nucleic Acids Res., 2017, 45(D1), D362-D368.
[http://dx.doi.org/10.1093/nar/gkw937] [PMID: 27924014]
[32]
Shannon, P.; Markiel, A. Owen Ozier, Nitin S. Baliga, Jonathan T. Wang, D.R.; Amin, N.; Schwikowski, B. Cytoscape: A software environment for integrated models of biomolecular interaction networks. Genome Res., 1971, 13, 426.
[33]
Chin, C.H.; Chen, S.H.; Wu, H.H.; Ho, C.W.; Ko, M.T.; Lin, C.Y. cytoHubba: identifying hub objects and sub-networks from complex interactome. BMC Syst. Biol., 2014, 8(Suppl. 4), S11.
[http://dx.doi.org/10.1186/1752-0509-8-S4-S11] [PMID: 25521941]
[34]
Raudvere, U.; Kolberg, L.; Kuzmin, I.; Arak, T.; Adler, P.; Peterson, H.; Vilo, J. g:Profiler: a web server for functional enrichment analysis and conversions of gene lists (2019 update). Nucleic Acids Res., 2019, 47(W1), W191-W198.
[http://dx.doi.org/10.1093/nar/gkz369] [PMID: 31066453]
[35]
Zhou, G.; Soufan, O.; Ewald, J.; Hancock, R.E.W.; Basu, N.; Xia, J. NetworkAnalyst 3.0: a visual analytics platform for comprehensive gene expression profiling and meta-analysis. Nucleic Acids Res., 2019, 47(W1), W234-W241.
[http://dx.doi.org/10.1093/nar/gkz240] [PMID: 30931480]
[36]
Tang, Z.; Kang, B.; Li, C.; Chen, T.; Zhang, Z. GEPIA2: an enhanced web server for large-scale expression profiling and interactive analysis. Nucleic Acids Res., 2019, 47(W1), W556-W560.
[http://dx.doi.org/10.1093/nar/gkz430] [PMID: 31114875]
[37]
Berman, H.M.; Westbrook, J.; Feng, Z.; Gilliland, G.; Bhat, T.N.; Weissig, H.; Shindyalov, I.N.; Bourne, P.E. The protein data bank Nucleic Acids Res., 2000, 28(1), 235-42.
[http://dx.doi.org/10.1093/nar/28.1.235]
[38]
Waterhouse, A.; Bertoni, M.; Bienert, S.; Studer, G.; Tauriello, G.; Gumienny, R.; Heer, F.T.; de Beer, T.A.P.; Rempfer, C.; Bordoli, L.; Lepore, R.; Schwede, T. SWISS-MODEL: homology modelling of protein structures and complexes. Nucleic Acids Res., 2018, 46(W1), W296-W303.
[http://dx.doi.org/10.1093/nar/gky427] [PMID: 29788355]
[39]
Kim, S.; Chen, J.; Cheng, T.; Gindulyte, A.; He, J.; He, S.; Li, Q.; Shoemaker, B.A.; Thiessen, P.A.; Yu, B.; Zaslavsky, L.; Zhang, J.; Bolton, E.E. PubChem 2019 update: improved access to chemical data. Nucleic Acids Res., 2019, 47(D1), D1102-D1109.
[http://dx.doi.org/10.1093/nar/gky1033] [PMID: 30371825]
[40]
Visualizer, D.S. v4. 0. 100. 13345 Accelrys Sof Tware Inc. 2005.
[41]
Dolinsky, T.J.; Czodrowski, P.; Li, H.; Nielsen, J.E.; Jensen, J.H.; Klebe, G.; Baker, N.A. PDB2PQR: expanding and upgrading automated preparation of biomolecular structures for molecular simulations. Nucleic Acids Res., 2007, 35, W522-W525.
[http://dx.doi.org/10.1093/nar/gkm276] [PMID: 17488841]
[42]
Gordon, J.C.; Myers, J.B.; Folta, T.; Shoja, V.; Heath, L.S.; Onufriev, A. H++: a server for estimating pKas and adding missing hydrogens to macromolecules. Nucleic Acids Res., 2005, 33, W368-W371.
[http://dx.doi.org/10.1093/nar/gki464] [PMID: 15980491]
[43]
Morris, G.M.; Huey, R.; Fau - Lindstrom,, W.; Lindstrom W Fau - Sanner, M.F.; Sanner Mf Fau - Belew, R.K.; Belew Rk Fau - Goodsell, D.S.; Goodsell Ds Fau - Olson, A.J.; Olson, A.J.; Chem, J.C. AutoDock4 and AutoDockTools4: Automated docking with selective receptor flexibility. J. Comput. Chem., 2009, 30, 2785-2791.
[http://dx.doi.org/10.1002/jcc.21256]
[44]
Oleg, T.; Arthur, J. O. AutoDock Vina: Improving the speed and accuracy of docking with a new scoring function, efficient optimisation, and multithreading. J. Comput. Chem., 2010, 31, 455-461.
[http://dx.doi.org/10.1002%2Fjcc.21334]
[45]
Delano, W.L.; Bromberg, S. PyMOL User’s Guide; , 2004.
[46]
Cress, W.D.; Yu, P.; Wu, J. Expression and alternative splicing of the cyclin-dependent kinase inhibitor-3 gene in human cancer. Int. J. Biochem. Cell Biol., 2017, 91(Pt B), 98-101.
[http://dx.doi.org/10.1016/j.biocel.2017.05.013] [PMID: 28504190]
[47]
Dai, W.; Miao, H.; Fang, S.; Fang, T.; Chen, N.; Li, M. CDKN3 expression is negatively associated with pathological tumor stage and CDKN3 inhibition promotes cell survival in hepatocellular carcinoma. Mol. Med. Rep., 2016, 14(2), 1509-1514.
[http://dx.doi.org/10.3892/mmr.2016.5410] [PMID: 27314282]
[48]
Xing, C.; Xie, H.; Zhou, L.; Zhou, W.; Zhang, W.; Ding, S.; Wei, B.; Yu, X.; Su, R.; Zheng, S. Cyclin-dependent kinase inhibitor 3 is overexpressed in hepatocellular carcinoma and promotes tumor cell proliferation. Biochem. Biophys. Res. Commun., 2012, 420(1), 29-35.
[http://dx.doi.org/10.1016/j.bbrc.2012.02.107] [PMID: 22390936]
[49]
Zhang, S.Y.; Lin, B.D.; Li, B.R. Evaluation of the diagnostic value of alpha‐ L ‐fucosidase, alpha‐fetoprotein and thymidine kinase 1 with ROC and logistic regression for hepatocellular carcinoma. FEBS Open Biol, 2015, 5(1), 240-244.
[http://dx.doi.org/10.1016/j.fob.2015.03.010] [PMID: 25870783]
[50]
Shen-Jie, J.I. L.G. The diagnostic value of joint detection of serum AFP, CA125 and TK1 in patients with primary hepatic carcinoma. J. Trop. Med., 2018. Available from: http://en.cnki.com.cn/Article_en/CJFDTotal-RDYZ201811020.htm
[51]
Zhang, Q.; Su, R.; Shan, C.; Gao, C.; Wu, P. Non-SMC Condensin I Complex, Subunit G (NCAPG) is a Novel Mitotic Gene Required for Hepatocellular Cancer Cell Proliferation and Migration. Oncol. Res., 2018, 26(2), 269-276.
[http://dx.doi.org/10.3727/096504017X15075967560980] [PMID: 29046167]
[52]
Liu, W.; Liang, B.; Liu, H.; Huang, Y.; Yin, X.; Zhou, F.; Yu, X.; Feng, Q.; Li, E.; Zou, Z.; Wu, L. Overexpression of non-SMC condensin I complex subunit G serves as a promising prognostic marker and therapeutic target for hepatocellular carcinoma. Int. J. Mol. Med., 2017, 40(3), 731-738.
[http://dx.doi.org/10.3892/ijmm.2017.3079] [PMID: 28737823]
[53]
Hou, S.; Chen, X.; Li, M.; Huang, X.; Liao, H.; Tian, B. Higher expression of cell division cycle-associated protein 5 predicts poorer survival outcomes in hepatocellular carcinoma. Aging (Albany NY), 2020, 12(14), 14542-14555.
[http://dx.doi.org/10.18632/aging.103501] [PMID: 32694239]
[54]
Chen, J.; Rajasekaran, M.; Xia, H.; Zhang, X.; Kong, S.N.; Sekar, K.; Seshachalam, V.P.; Deivasigamani, A.; Goh, B.K.P.; Ooi, L.L.; Hong, W.; Hui, K.M. The microtubule-associated protein PRC1 promotes early recurrence of hepatocellular carcinoma in association with the Wnt/β-catenin signalling pathway. Gut, 2016, 65(9), 1522-1534.
[http://dx.doi.org/10.1136/gutjnl-2015-310625] [PMID: 26941395]
[55]
Zhou, Z.; Li, Y.; Hao, H.; Wang, Y.; Zhou, Z.; Wang, Z.; Chu, X. Screening hub genes as prognostic biomarkers of hepatocellular carcinoma by bioinformatics analysis. Cell Transplant., 2019, 28(S1), 76-86.
[http://dx.doi.org/10.1177/0963689719893950]
[56]
Vader, G.; Lens, S.M.A. The Aurora kinase family in cell division and cancer. Biochim. Biophys. Acta Rev. Cancer, 2008, 1786(1), 60-72.
[http://dx.doi.org/10.1016/j.bbcan.2008.07.003] [PMID: 18662747]
[57]
Li, X.; Xu, W.; Kang, W.; Wong, S.H.; Wang, M.; Zhou, Y.; Fang, X.; Zhang, X.; Yang, H.; Wong, C.H.; To, K.F.; Chan, S.L.; Chan, M.T.V.; Sung, J.J.Y.; Wu, W.K.K.; Yu, J. Genomic analysis of liver cancer unveils novel driver genes and distinct prognostic features. Theranostics, 2018, 8(6), 1740-1751.
[http://dx.doi.org/10.7150/thno.22010] [PMID: 29556353]
[58]
Simon, E.P.; Freije, C.A.; Farber, B.A.; Lalazar, G.; Darcy, D.G.; Honeyman, J.N.; Chiaroni-Clarke, R.; Dill, B.D.; Molina, H.; Bhanot, U.K.; La Quaglia, M.P.; Rosenberg, B.R.; Simon, S.M. Transcriptomic characterization of fibrolamellar hepatocellular carcinoma. Proc. Natl. Acad. Sci. USA, 2015, 112(44), E5916-E5925.
[http://dx.doi.org/10.1073/pnas.1424894112] [PMID: 26489647]
[59]
Chen, C.; Song, G.; Xiang, J.; Zhang, H.; Zhao, S.; Zhan, Y. AURKA promotes cancer metastasis by regulating epithelial-mesenchymal transition and cancer stem cell properties in hepatocellular carcinoma. Biochem. Biophys. Res. Commun., 2017, 486(2), 514-520.
[http://dx.doi.org/10.1016/j.bbrc.2017.03.075] [PMID: 28322787]
[60]
Zhang, K.; Chen, J.; Chen, D.; Huang, J.; Feng, B.; Han, S.; Chen, Y.; Song, H.; De, W.; Zhu, Z.; Wang, R.; Chen, L. Aurora-A promotes chemoresistance in hepatocelluar carcinoma by targeting NF-kappaB/microRNA-21/PTEN signaling pathway. Oncotarget, 2014, 5(24), 12916-12935.
[http://dx.doi.org/10.18632/oncotarget.2682] [PMID: 25428915]
[61]
Wang, S.M.; Ooi, L.L.P.J.; Hui, K.M. Upregulation of Rac GTPase-activating protein 1 is significantly associated with the early recurrence of human hepatocellular carcinoma. Clin. Cancer Res., 2011, 17(18), 6040-6051.
[http://dx.doi.org/10.1158/1078-0432.CCR-11-0557] [PMID: 21825042]
[62]
Li, B.; Pu, K.; Wu, X. Identifying novel biomarkers in hepatocellular carcinoma by weighted gene co‐expression network analysis. J. Cell. Biochem., 2019, 120(7), 11418-11431.
[http://dx.doi.org/10.1002/jcb.28420] [PMID: 30746803]
[63]
Zhao, X.; Weng, W.; Jin, M.; Li, S.; Chen, Q.; Li, B.; Zhou, Z.; Lan, C.; Yang, Y. Identification of Biomarkers Based on Bioinformatics Analysis: The Expression of Ubiquitin-Conjugating Enzyme E2T (UBE2T) in the carcinogenesis and progression of hepatocellular carcinoma. Med. Sci. Monit., 2021, 27, e929023.
[http://dx.doi.org/10.12659/MSM.929023] [PMID: 33658475]
[64]
Xia, H.; Kong, S.N.; Chen, J.; Shi, M.; Sekar, K.; Seshachalam, V.P.; Rajasekaran, M.; Goh, B.K.P.; Ooi, L.L.; Hui, K.M. MELK is an oncogenic kinase essential for early hepatocellular carcinoma recurrence. Cancer Lett., 2016, 383(1), 85-93.
[http://dx.doi.org/10.1016/j.canlet.2016.09.017] [PMID: 27693640]
[65]
Hiwatashi, K.; Ueno, S.; Sakoda, M.; Iino, S.; Minami, K.; Yonemori, K.; Nishizono, Y.; Kurahara, H.; Mataki, Y.; Maemura, K.; Shinchi, H.; Natsugoe, S. Expression of maternal embryonic leucine zipper kinase (MELK) correlates to malignant potentials in hepatocellular carcinoma. Anticancer Res., 2016, 36(10), 5183-5188.
[http://dx.doi.org/10.21873/anticanres.11088] [PMID: 27798878]
[66]
Lin, S.Y.; Pan, H.W.; Liu, S.H.; Jeng, Y.M.; Hu, F.C.; Peng, S.Y.; Lai, P.L.; Hsu, H.C. ASPM is a novel marker for vascular invasion, early recurrence, and poor prognosis of hepatocellular carcinoma. Clin. Cancer Res., 2008, 14(15), 4814-4820.
[http://dx.doi.org/10.1158/1078-0432.CCR-07-5262] [PMID: 18676753]
[67]
Wu, B.; Hu, C.; Kong, L. ASPM combined with KIF11 promotes the malignant progression of hepatocellular carcinoma via the Wnt/β-catenin signaling pathway. Exp. Ther. Med., 2021, 22(4), 1154.
[http://dx.doi.org/10.3892/etm.2021.10588] [PMID: 34504599]
[68]
Xu, Z.Y.; Ding, S.M.; Zhou, L.; Xie, H.Y.; Chen, K.J.; Zhang, W.; Xing, C.Y.; Guo, H.J.; Zheng, S.S. FOXC1 contributes to microvascular invasion in primary hepatocellular carcinoma via regulating epithelial-mesenchymal transition. Int. J. Biol. Sci., 2012, 8(8), 1130-1141.
[http://dx.doi.org/10.7150/ijbs.4769] [PMID: 22991501]
[69]
Xia, L.; Huang, W.; Tian, D.; Zhu, H.; Qi, X.; Chen, Z.; Zhang, Y.; Hu, H.; Fan, D.; Nie, Y.; Wu, K. Overexpression of forkhead box C1 promotes tumor metastasis and indicates poor prognosis in hepatocellular carcinoma. Hepatology, 2013, 57(2), 610-624.
[http://dx.doi.org/10.1002/hep.26029] [PMID: 22911555]
[70]
Lin, Z.; Huang, W.; He, Q.; Li, D.; Wang, Z.; Feng, Y.; Liu, D.; Zhang, T.; Wang, Y.; Xie, M.; Ji, X.; Sun, M.; Tian, D.; Xia, L. FOXC1 promotes HCC proliferation and metastasis by Upregulating DNMT3B to induce DNA Hypermethylation of CTH promoter. J. Exp. Clin. Cancer Res., 2021, 40(1), 50.
[http://dx.doi.org/10.1186/s13046-021-01829-6] [PMID: 33522955]
[71]
Ray, P.S.; Wang, J.; Qu, Y.; Sim, M.S.; Shamonki, J.; Bagaria, S.P.; Ye, X.; Liu, B.; Elashoff, D.; Hoon, D.S.; Walter, M.A.; Martens, J.W.; Richardson, A.L.; Giuliano, A.E.; Cui, X. FOXC1 is a potential prognostic biomarker with functional significance in basal-like breast cancer. Cancer Res., 2010, 70(10), 3870-3876.
[http://dx.doi.org/10.1158/0008-5472.CAN-09-4120] [PMID: 20406990]
[72]
Xu, Y.; Shao, Q.; Yao, H.; Jin, Y.; Ma, Y.; Jia, L. Overexpression of FOXC1 correlates with poor prognosis in gastric cancer patients. Histopathology, 2014, 64(7), 963-970.
[http://dx.doi.org/10.1111/his.12347] [PMID: 24329718]
[73]
Ou-Yang, L.; Xiao, S.J.; Liu, P.; Yi, S.J.; Zhang, X.L.; Ou-Yang, S.; Tan, S.K.; Lei, X. Forkhead box C1 induces epithelial-mesenchymal transition and is a potential therapeutic target in nasopharyngeal carcinoma. Mol. Med. Rep., 2015, 12(6), 8003-8009.
[http://dx.doi.org/10.3892/mmr.2015.4427] [PMID: 26461269]
[74]
Wang, L.Y.; Li, L.S.; Yang, Z. Correlation of FOXC1 protein with clinicopathological features in serous ovarian tumors. Oncol. Lett., 2016, 11(2), 933-938.
[http://dx.doi.org/10.3892/ol.2015.3996] [PMID: 26893671]
[75]
Li, Y.W.; Wang, J.X.; Yin, X.; Qiu, S.J.; Wu, H.; Liao, R.; Yi, Y.; Xiao, Y.S.; Zhou, J.; Zhang, B.H.; Fan, J. Decreased expression of GATA2 promoted proliferation, migration and invasion of HepG2 in vitro and correlated with poor prognosis of hepatocellular carcinoma. PLoS One, 2014, 9(1), e87505.
[http://dx.doi.org/10.1371/journal.pone.0087505] [PMID: 24498120]
[76]
Song, S.H.; Jeon, M.S.; Nam, J.W.; Kang, J.K.; Lee, Y.J.; Kang, J.Y.; Kim, H.P.; Han, S.W.; Kang, G.H.; Kim, T.Y. Aberrant GATA2 epigenetic dysregulation induces a GATA2/GATA6 switch in human gastric cancer. Oncogene, 2018, 37(8), 993-1004.
[http://dx.doi.org/10.1038/onc.2017.397] [PMID: 29106391]
[77]
Rodriguez-Bravo, V.; Carceles-Cordon, M.; Hoshida, Y.; Cordon-Cardo, C.; Galsky, M.D.; Domingo-Domenech, J. The role of GATA2 in lethal prostate cancer aggressiveness. Nat. Rev. Urol., 2017, 14(1), 38-48.
[http://dx.doi.org/10.1038/nrurol.2016.225] [PMID: 27872477]
[78]
Peters, I.; Dubrowinskaja, N.; Tezval, H.; Kramer, M.W.; von Klot, C.A.; Hennenlotter, J.; Stenzl, A.; Scherer, R.; Kuczyk, M.A.; Serth, J. Decreased mRNA expression of GATA1 and GATA2 is associated with tumor aggressiveness and poor outcome in clear cell renal cell carcinoma. Target. Oncol., 2015, 10(2), 267-275.
[http://dx.doi.org/10.1007/s11523-014-0335-8] [PMID: 25230694]
[79]
Tessema, M.; Yingling, C.M.; Snider, A.M.; Do, K.; Juri, D.E.; Picchi, M.A.; Zhang, X.; Liu, Y.; Leng, S.; Tellez, C.S.; Belinsky, S.A. GATA2 is epigenetically repressed in human and mouse lung tumors and is not requisite for survival of KRAS mutant lung cancer. J. Thorac. Oncol., 2014, 9(6), 784-793.
[http://dx.doi.org/10.1097/JTO.0000000000000165] [PMID: 24807155]
[80]
Dong, M.; Xin, Y.; Zhuang, L. Role, regulatory mechanism and clinical correlation of YY1 in HCC; Benjamin Bonavida. In: YY1 in the Control of the Pathogenesis and Drug Resistance of Cancer; Academic Press, 2021; pp. Pages 199-207. ISBN 9780128219096
[http://dx.doi.org/10.1016/B978-0-12-821909-6.00022-5]
[81]
Huang, T.; Wang, G.; Yang, L.; Peng, B.; Wen, Y.; Ding, G.; Wang, Z. Transcription Factor YY1 Modulates Lung Cancer Progression by Activating lncRNA-PVT1. DNA Cell Biol., 2017, 36(11), 947-958.
[http://dx.doi.org/10.1089/dna.2017.3857] [PMID: 28972861]
[82]
Wan, M.; Huang, W.; Kute, T.E.; Miller, L.D.; Zhang, Q.; Hatcher, H.; Wang, J.; Stovall, D.B.; Russell, G.B.; Cao, P.D.; Deng, Z.; Wang, W.; Zhang, Q.; Lei, M.; Torti, S.V.; Akman, S.A.; Sui, G. Yin Yang 1 plays an essential role in breast cancer and negatively regulates p27. Am. J. Pathol., 2012, 180(5), 2120-2133.
[http://dx.doi.org/10.1016/j.ajpath.2012.01.037] [PMID: 22440256]
[83]
Cui, S.; Zhang, K.; Li, C.; Chen, J.; Pan, Y.; Feng, B.; Lu, L.; Zhu, Z.; Wang, R.; Chen, L. Methylation-associated silencing of microRNA-129-3p promotes epithelial-mesenchymal transition, invasion and metastasis of hepatocelluar cancer by targeting Aurora-A. Oncotarget, 2016, 7(47), 78009-78028.
[http://dx.doi.org/10.18632/oncotarget.12870] [PMID: 27793005]
[84]
Cheng, B.; Ding, F.; Huang, C.Y.; Xiao, H.; Fei, F.Y.; Li, J. Role of miR-16-5p in the proliferation and metastasis of hepatocellular carcinoma. Eur. Rev. Med. Pharmacol. Sci., 2019, 23(1), 137-145.
[http://dx.doi.org/10.26355/eurrev_201901_16757] [PMID: 30657555]
[85]
Long, H.D.; Ma, Y.S.; Yang, H.Q.; Xue, S.B.; Liu, J.B.; Yu, F.; Lv, Z.W.; Li, J.Y.; Xie, R.T.; Chang, Z.Y.; Lu, G.X.; Xie, W.T.; Fu, D.; Pang, L.J. Reduced hsa-miR-124-3p levels are associated with the poor survival of patients with hepatocellular carcinoma. Mol. Biol. Rep., 2018, 45(6), 2615-2623.
[http://dx.doi.org/10.1007/s11033-018-4431-1] [PMID: 30341691]
[86]
Wong, T.S.; Liu, X.B.; Wong, B.Y.H.; Ng, R.W.M.; Yuen, A.P.W.; Wei, W.I. Mature miR-184 as potential oncogenic microRNA of squamous cell carcinoma of tongue. Clin. Cancer Res., 2008, 14(9), 2588-2592.
[http://dx.doi.org/10.1158/1078-0432.CCR-07-0666] [PMID: 18451220]
[87]
Li, H.; Huhe, M.; Lou, J. MicroRNA-103a-3p promotes cell proliferation and invasion in non-small-cell lung cancer cells through Akt pathway by targeting PTEN. BioMed Res. Int., 2021, 2021, 7590976.
[http://dx.doi.org/10.1155/2021/7590976] [PMID: 34307670]
[88]
Grant, T.J.; Bishop, J.A.; Christadore, L.M.; Barot, G.; Chin, H.G.; Woodson, S.; Kavouris, J.; Siddiq, A.; Gredler, R.; Shen, X.N.; Sherman, J.; Meehan, T.; Fitzgerald, K.; Pradhan, S.; Briggs, L.A.; Andrews, W.H.; Sarkar, D.; Schaus, S.E.; Hansen, U. Antiproliferative small-molecule inhibitors of transcription factor LSF reveal oncogene addiction to LSF in hepatocellular carcinoma. Proc. Natl. Acad. Sci. USA, 2012, 109(12), 4503-4508.
[http://dx.doi.org/10.1073/pnas.1121601109] [PMID: 22396589]
[89]
Golberg, A.; Sheviryov, J.; Solomon, O.; Anavy, L.; Yakhini, Z. Molecular harvesting with electroporation for tissue profiling. Sci. Rep., 2019, 9(1), 15750.
[http://dx.doi.org/10.1038/s41598-019-51634-7] [PMID: 31673038]
[90]
Wan, Z.; Zhang, X.; Luo, Y.; Zhao, B. Identification of hepatocellular carcinoma-related potential genes and pathways through bioinformatic-based analyses. Genet. Test. Mol. Biomarkers, 2019, 23(11), 766-777.
[http://dx.doi.org/10.1089/gtmb.2019.0063] [PMID: 31633428]
[91]
Li, H.T.; Wei, B.; Li, Z.Q.; Wang, X.; Jia, W.X.; Xu, Y.Z.; Liu, J.Y.; Shao, M.N.; Chen, S.X.; Mo, N.F.; Zhao, D.; Zuo, W.P.; Qin, J.; Li, P.; Zhang, Q.L.; Yang, X.L. Diagnostic and prognostic value of MCM3 and its interacting proteins in hepatocellular carcinoma. Oncol. Lett., 2020, 20(6), 1.
[http://dx.doi.org/10.3892/ol.2020.12171] [PMID: 33093917]
[92]
Bellisola, G.; Casaril, M.; Gabrielli, G.B.; Caraffi, M.; Corrocher, R. Catalase activity in human hepatocellular carcinoma (HCC). Clin. Biochem., 1987, 20(6), 415-417.
[http://dx.doi.org/10.1016/0009-9120(87)90007-5] [PMID: 2830048]
[93]
Chen, X.; Liao, L.; Li, Y.; Huang, H.; Huang, Q.; Deng, S. Screening and functional prediction of key candidate genes in Hepatitis B virus-associated hepatocellular carcinoma. BioMed Res. Int., 2020, 2020, 7653506.
[http://dx.doi.org/10.1155/2020/7653506] [PMID: 33102593]
[94]
Liu, S.; Yao, X.; Zhang, D.; Sheng, J.; Wen, X.; Wang, Q.; Chen, G.; Li, Z.; Du, Z.; Zhang, X. Analysis of transcription factor-related regulatory networks based on bioinformatics analysis and validation in hepatocellular carcinoma. BioMed Res. Int., 2018, 2018, 1431396.
[http://dx.doi.org/10.1155/2018/1431396] [PMID: 30228980]
[95]
Li, L.; Cheng, Y.; Lin, L.; Liu, Z.; Du, S.; Ma, L.; Li, J.; Peng, Z.; Yan, J. Global analysis of miRNA signature differentially expressed in insulin-resistant human hepatocellular carcinoma cell line. Int. J. Med. Sci., 2020, 17(5), 664-677.
[http://dx.doi.org/10.7150/ijms.41999] [PMID: 32210717]
[96]
Liu, J.; Li, G.; Guo, Y.; Fan, N.; Zang, Y. The association between genomic variations and histological grade in hepatocellular carcinoma. Transl. Cancer Res., 2020, 9(4), 2424-2433.
[http://dx.doi.org/10.21037/tcr.2020.03.32] [PMID: 35117602]
[97]
Huang, H.; Zhang, Q.; Zhang, Y.; Sun, X.; Liu, C.; Wang, Q.; Huang, Y.; Li, Q.; Wu, Z.; Pu, C.; Sun, A. Identification of the level of exosomal protein by parallel reaction monitoring technology in HCC patients. Int. J. Gen. Med., 2022, 15, 7831-7842.
[http://dx.doi.org/10.2147/IJGM.S384140] [PMID: 36267426]
[98]
Li, N.; Li, L.; Chen, Y. The identification of core gene expression signature in hepatocellular carcinoma. Oxid. Med. Cell. Longev., 2018, 2018, 3478305.
[http://dx.doi.org/10.1155/2018/3478305] [PMID: 29977454]
[99]
Peng, J.; Wu, J.; Li, G.; Wu, J.; Xi, Y.; Li, X.; Wang, L. Identification of potential biomarkers of peripheral blood mononuclear cell in hepatocellular carcinoma using bioinformatic analysis. Medicine (Baltimore), 2021, 100(2), e24172.
[http://dx.doi.org/10.1097/MD.0000000000024172] [PMID: 33466191]
[100]
Chen, J.; Qian, Z.; Li, F.; Li, J.; Lu, Y. Integrative analysis of microarray data to reveal regulation patterns in the pathogenesis of hepatocellular carcinoma. Gut Liver, 2017, 11(1), 112-120.
[http://dx.doi.org/10.5009/gnl16063] [PMID: 27458175]
[101]
Qiu, Q.C.; Wang, L.; Jin, S.S.; Liu, G.F.; Liu, J.; Ma, L.; Mao, R.F.; Ma, Y.Y.; Zhao, N.; Chen, M.; Lin, B.Y. CHI3L1 promotes tumor progression by activating TGF-β signaling pathway in hepatocellular carcinoma. Sci. Rep., 2018, 8(1), 15029.
[http://dx.doi.org/10.1038/s41598-018-33239-8] [PMID: 30301907]
[102]
Tai, Y.L.; Chen, K.C.; Hsieh, J.T.; Shen, T.L. Exosomes in cancer development and clinical applications. Cancer Sci., 2018, 109(8), 2364-2374.
[http://dx.doi.org/10.1111/cas.13697] [PMID: 29908100]
[103]
Xu, H.; Lam, S.H.; Shen, Y.; Gong, Z. Genome-wide identification of molecular pathways and biomarkers in response to arsenic exposure in zebrafish liver. PLoS One, 2013, 8(7), e68737.
[http://dx.doi.org/10.1371/journal.pone.0068737] [PMID: 23922661]
[104]
Yang, W.X.; Pan, Y.Y.; You, C.G. CDK1, CCNB1, CDC20, BUB1, MAD2L1, MCM3, BUB1B, MCM2, and RFC4 may be potential therapeutic targets for hepatocellular carcinoma using integrated bioinformatic analysis. BioMed Res. Int., 2019, 2019, 1245072.
[http://dx.doi.org/10.1155/2019/1245072] [PMID: 31737652]
[105]
Li, Z.; Lin, Y.; Cheng, B.; Zhang, Q.; Cai, Y. Identification and analysis of potential key genes associated with hepatocellular carcinoma based on integrated bioinformatics methods. Front. Genet., 2021, 12, 571231.
[http://dx.doi.org/10.3389/fgene.2021.571231] [PMID: 33767726]
[106]
Liu, J.; Han, F.; Ding, J.; Liang, X.; Liu, J.; Huang, D.; Zhang, C. Identification of multiple hub genes and pathways in hepatocellular carcinoma: A bioinformatics analysis. BioMed Res. Int., 2021, 2021, 8849415.
[http://dx.doi.org/10.1155/2021/8849415] [PMID: 34337056]
[107]
Jin, B.; Wang, W.; Du, G.; Huang, G.Z.; Han, L.T.; Tang, Z.Y.; Fan, D.G.; Li, J.; Zhang, S.Z. Identifying hub genes and dysregulated pathways in hepatocellular carcinoma. Eur. Rev. Med. Pharmacol. Sci., 2015, 19(4), 592-601.
[PMID: 25753876]
[108]
Yeh, H.W.; Lee, S.S.; Chang, C.Y.; Hu, C.M.; Jou, Y.S. Pyrimidine metabolic rate limiting enzymes in poorly-differentiated hepatocellular carcinoma are signature genes of cancer stemness and associated with poor prognosis. Oncotarget, 2017, 8(44), 77734-77751.
[http://dx.doi.org/10.18632/oncotarget.20774] [PMID: 29100421]
[109]
Ferroudj, S.; Yildiz, G.; Bouras, M.; Iscan, E.; Ekin, U.; Ozturk, M. Role of Fanconi anemia/BRCA pathway genes in hepatocellular carcinoma chemoresistance. Hepatol. Res., 2016, 46(12), 1264-1274.
[http://dx.doi.org/10.1111/hepr.12675] [PMID: 26885668]
[110]
Whelan, J.S.; Stebbings, W.; Owen, R.A.; Calne, R.; Clark, P.I. Successful treatment of a primary endodermal sinus tumor of the liver. Cancer, 1992, 70(9), 2260-2262.
[http://dx.doi.org/10.1002/1097-0142(19921101)70:9<2260:AID-CNCR2820700908>3.0.CO;2-Y] [PMID: 1382827]
[111]
Zhong, Y.; Qi, H.; Li, X.; An, M.; Shi, Q.; Qi, J. Tumor supernatant derived from hepatocellular carcinoma cells treated with vincristine sulfate have therapeutic activity. Eur. J. Pharm. Sci., 2020, 155, 105557.
[http://dx.doi.org/10.1016/j.ejps.2020.105557] [PMID: 32946955]
[112]
Aboubakr, E.M.; Taye, A.; Aly, O.M.; Gamal-Eldeen, A.M.; El-Moselhy, M.A. Enhanced anticancer effect of Combretastatin A-4 phosphate when combined with vincristine in the treatment of hepatocellular carcinoma. Biomed. Pharmacother., 2017, 89, 36-46.
[http://dx.doi.org/10.1016/j.biopha.2017.02.019] [PMID: 28214686]
[113]
Özdemir, F.; Akalın, G.; Şen, M.; Önder, N.I.; Işcan, A.; Kutlu, H.M.; Incesu, Z. Towards novel anti-tumor strategies for hepatic cancer: ɛ-viniferin in combination with vincristine displays pharmacodynamic synergy at lower doses in HepG2 cells. OMICS, 2014, 18(5), 324-334.
[http://dx.doi.org/10.1089/omi.2013.0045] [PMID: 24341688]
[114]
Wang, Z.; Zhou, J.; Fan, J.; Tan, C.J.; Qiu, S.J.; Yu, Y.; Huang, X.W.; Tang, Z.Y. Sirolimus inhibits the growth and metastatic progression of hepatocellular carcinoma. J. Cancer Res. Clin. Oncol., 2009, 135(5), 715-722.
[http://dx.doi.org/10.1007/s00432-008-0506-z] [PMID: 19002496]
[115]
Chinnakotla, S.; Davis, G.L.; Vasani, S.; Kim, P.; Tomiyama, K.; Sanchez, E.; Onaca, N.; Goldstein, R.; Levy, M.; Klintmalm, G.B. Impact of sirolimus on the recurrence of hepatocellular carcinoma after liver transplantation. Liver Transpl., 2009, 15(12), 1834-1842.
[http://dx.doi.org/10.1002/lt.21953] [PMID: 19938137]
[116]
Lee, K.W.; Kim, S.H.; Yoon, K.C.; Lee, J.M.; Cho, J.H.; Hong, S.K.; Yi, N.J.; Han, S.S.; Park, S.J.; Suh, K.S. Sirolimus prolongs survival after living donor liver transplantation for hepatocellular carcinoma beyond milan criteria: A prospective, randomised, open-label, multicentre Phase 2 Trial. J. Clin. Med., 2020, 9(10), 3264.
[http://dx.doi.org/10.3390/jcm9103264] [PMID: 33053849]

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