Abstract
Background: Hepatocellular Carcinoma (HCC) is one of the fastest-growing malignancies globally. The impact of surgical treatment is limited, and molecular targeted therapy has not yielded a consistent efficacy. This warrants for identification of novel molecular targets. The Anti- Silencing Function of 1B histone chaperone (ASF1B) was previously studied in numerous cancers. However, the understanding of its role in HCC is limited.
Methods: The TIMER database was used to analyze the ASF1B expression in pan-cancer and paracarcinoma tissues. ASF1B expression in HCC was confirmed using the HCCDB database, Quantitative real-time PCR (q-PCR), and Western Blot (WB) assays. The relationship between clinicopathological parameters and ASF1B expression was analyzed using UALCAN, whereas the prognostic value of ASF1B was evaluated using the GEPIA database. Linkedomics and cBioPortal databases were used to validate the ASF1B co-expression associated with immune infiltration by the TIMER database. Moreover, cell proliferation after ASF1B-knockdown was determined through CCK8 and clone formation assays.
Results: ASF1B was highly expressed in HCC tissues, and the expression levels were linked to tumor grade, race, and disease stage. Univariate and multivariate Cox models showed that ASF1B is an independent prognostic factor in HCC. CCK8 and clone formation assays demonstrated that ASF1B promotes cell proliferation. Gene co-expression analysis in Linkedomics demonstrated that HJURP, KIF2C, KIF4A, KIF18B, and KIFC1 expressions were closely associated with ASF1B and immune infiltrate cells.
Conclusion: This study shows that ASF1B promotes the proliferation of HCC. Besides, ASF1B could be a potential prognostic biomarker for HCC patients.
Keywords: ASF1B, Hepatocellular Carcinoma, prognosis, bioinformatics, immune, GSEA
Graphical Abstract
[http://dx.doi.org/10.3322/caac.21654] [PMID: 33433946]
[http://dx.doi.org/10.1053/j.gastro.2011.12.061] [PMID: 22537432]
[http://dx.doi.org/10.1016/j.jhep.2013.08.011] [PMID: 23978719]
[http://dx.doi.org/10.1016/S0140-6736(14)61838-9] [PMID: 25433429]
[http://dx.doi.org/10.1038/990147] [PMID: 10591219]
[http://dx.doi.org/10.1126/science.1148992] [PMID: 18096807]
[http://dx.doi.org/10.1016/j.tcb.2008.10.002] [PMID: 19027300]
[http://dx.doi.org/10.1016/j.cell.2010.01.004] [PMID: 20141833]
[http://dx.doi.org/10.1074/jbc.M303549200] [PMID: 12842904]
[http://dx.doi.org/10.1038/s41419-020-02872-5] [PMID: 32848135]
[http://dx.doi.org/10.1038/emboj.2010.335] [PMID: 21179005]
[http://dx.doi.org/10.1158/0008-5472.CAN-17-0307] [PMID: 29092952]
[http://dx.doi.org/10.1038/nmeth.1226] [PMID: 18516045]
[http://dx.doi.org/10.1016/j.gpb.2018.07.003] [PMID: 30266410]
[http://dx.doi.org/10.1016/j.neo.2017.05.002] [PMID: 28732212]
[http://dx.doi.org/10.1093/nar/gkx247] [PMID: 28407145]
[http://dx.doi.org/10.1093/nar/gkx1090] [PMID: 29136207]
[http://dx.doi.org/10.1126/scisignal.2004088] [PMID: 23550210]
[http://dx.doi.org/10.4103/0970-0218.106630] [PMID: 23559706]
[http://dx.doi.org/10.3322/caac.21660] [PMID: 33538338]
[http://dx.doi.org/10.1158/0008-5472.CAN-16-1508] [PMID: 27993818]
[http://dx.doi.org/10.1002/hep.22160] [PMID: 18176954]
[http://dx.doi.org/10.1002/hep.28417] [PMID: 26698646]
[http://dx.doi.org/10.2147/OTT.S241627] [PMID: 32764956]
[http://dx.doi.org/10.3892/ijo.2018.4526] [PMID: 30132513]
[PMID: 35087760]
[http://dx.doi.org/10.1186/s13046-018-0866-4] [PMID: 30111352]
[http://dx.doi.org/10.1007/s13238-020-00766-y] [PMID: 32748349]
[http://dx.doi.org/10.1038/s41419-017-0114-4] [PMID: 29396392]
[http://dx.doi.org/10.1002/jcp.29444] [PMID: 32052444]
[http://dx.doi.org/10.1186/s13046-019-1331-8] [PMID: 31340839]
[http://dx.doi.org/10.1080/15384047.2018.1433501] [PMID: 29400599]
[http://dx.doi.org/10.1016/j.cell.2017.05.035] [PMID: 28622514]
[PMID: 33415021]