Data mining of key genes expression in hepatocellular carcinoma: novel potential biomarkers of diagnosis prognosis or progression.
Data mining
HCC
Key genes
Osteopontin
Journal
Clinical & experimental metastasis
ISSN: 1573-7276
Titre abrégé: Clin Exp Metastasis
Pays: Netherlands
ID NLM: 8409970
Informations de publication
Date de publication:
08 2022
08 2022
Historique:
received:
06
12
2021
accepted:
22
03
2022
pubmed:
17
4
2022
medline:
3
8
2022
entrez:
16
4
2022
Statut:
ppublish
Résumé
Hepatocellular carcinoma (HCC) is one of the main cancer-related causes of death worldwide. The study aimed to perform a data mining analysis of the expression and regulatory role of key genes in HCC to reveal novel potential biomarkers of diagnosis prognosis, or progression since their availability is still almost lacking. Starting from data of our cohort of patients (HCV-positive HCC pts undergoing liver transplantation (LR, n = 10) and donors (LD, n = 14), deeply analyzed previously, in which apelin, osteopontin, osteoprotegerin, NOTCH-1, CASP-3, Bcl-2, BAX, PTX3, and NPTX2 were analyzed, we applied statistical analysis and in-silico tools (Gene Expression Profiling Interactive Analysis, HCCDB database and GeneMania, UALCAN) to screen and identify the key genes. Firstly, we performed a stepwise regression analysis using our mRNA-datasets which revealed that higher expression levels of apelin and osteopontin were positively associated with the HCC and identified that the most consistently differentially expressed gene across multiple HCC expression datasets was only OPN. This comprehensive strategy of data mining evidenced that OPN might have a potential function as an important tumor marker-driven oncogenesis being associated with poor prognosis of HCC patients.
Identifiants
pubmed: 35429302
doi: 10.1007/s10585-022-10164-9
pii: 10.1007/s10585-022-10164-9
pmc: PMC9338913
doi:
Substances chimiques
Apelin
0
Biomarkers, Tumor
0
Osteopontin
106441-73-0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
589-602Informations de copyright
© 2022. The Author(s).
Références
Bruix J, Sherman M (2011) Management of hepatocellular carcinoma: an update. Hepatology 53:1020–1022. https://doi.org/10.1002/hep.24199
doi: 10.1002/hep.24199
pubmed: 21374666
Garuti F, Neri A, Avanzato F, Gramenzi A, Rampoldi D, Rucci P, Farinati F, Giannini EG, Piscaglia F, Rapaccini GL, Di Marco M, Caturelli E, Zoli M, Sacco R, Cabibbo G, Marra F, Mega A, Morisco F, Gasbarrini A, Svegliati-Baroni G, Foschi FG, Missale G, Masotto A, Nardone G, Raimondo G, Azzaroli F, Vidili G, Brunetto MR, Trevisani F, ITA.LI.CA study group (2021) The changing scenario of hepatocellular carcinoma in Italy: an update. Liver Int 41:585–597. https://doi.org/10.1111/liv.14735
doi: 10.1111/liv.14735
pubmed: 33219585
European Association for the Study of the Liver (2018) EASL clinical practice guidelines: management of hepatocellular carcinoma. J Hepatol 69:182–236. https://doi.org/10.1016/j.jhep.2018.03.019
doi: 10.1016/j.jhep.2018.03.019
Members of the AIOM Guidelines Writing Committee on Hepatocellular Carcinoma Guidelines of the Italian Medical Oncology Association (AIOM) on Hepatocellular Carcinoma, Ed. (2019)
Younossi Z, Stepanova M, Ong JP, Jacobson IM, Bugianesi E, Duseja A, Eguchi Y, Wong VW, Negro F, Yilmaz Y, Romero-Gomez M, George J, Ahmed A, Wong R, Younossi I, Ziayee M, Afendy A, Council GNS (2019) Nonalcoholic steatohepatitis is the fastest growing cause of hepatocellular carcinoma in liver transplant candidates. Clin Gastroenterol Hepatol 17:748–755. https://doi.org/10.1016/j.cgh.2018.05.057
doi: 10.1016/j.cgh.2018.05.057
pubmed: 29908364
Peiseler M, Tacke F (2021) Inflammatory mechanisms underlying nonalcoholic steatohepatitis and the transition to hepatocellular carcinoma. Cancers 13:730. https://doi.org/10.3390/cancers13040730
doi: 10.3390/cancers13040730
pubmed: 33578800
pmcid: 7916589
Yang YY, Xie L, Zhang NP, Zhou D, Liu TT, Wu J (2022) Updates on novel pharmacotherapeutics for the treatment of nonalcoholic steatohepatitis. Acta Pharmacol Sin. https://doi.org/10.1038/s41401-022-00860-3
doi: 10.1038/s41401-022-00860-3
pubmed: 36229599
pmcid: 9525278
Joshi K, Kohli A, Manch R, Gish R (2016) Alcoholic liver disease: high risk or low risk for developing hepatocellular carcinoma? Clin Liver Dis 20:563–580. https://doi.org/10.1016/j.cld.2016.02.012
doi: 10.1016/j.cld.2016.02.012
pubmed: 27373617
Lok AS, Seeff LB, Morgan TR, Di Bisceglie AM, Sterlng RK, Curto TM, Everson GT, Lindsay KL, Lee WM, Bonkovsky HL, Dienstag JL, Ghany MG, Morishima C, Goodman ZD, HALT-C Trial Group (2009) Incidence of hepatocellular carcinoma and associated risk factors in hepatitis C-related advanced liver disease. Gastroenterology 136:138–148. https://doi.org/10.1053/j.gastro.2008.09.014
doi: 10.1053/j.gastro.2008.09.014
pubmed: 18848939
Ružić M, Pellicano R, Fabri M, Luzza F, Boccuto L, Brkić S, Abenavoli L (2018) Hepatitis C virus-induced hepatocellular carcinoma: a narrative review. Panminerva Med 60:185–191. https://doi.org/10.23736/S0031-0808.18.03472-9
doi: 10.23736/S0031-0808.18.03472-9
pubmed: 29856183
Jung KS, Kim SU, Ahn SH, Park YN, Kim DY, Park JY, Chon CY, Choi EH, Han HKH (2011) Risk assessment of hepatitis B virus-related hepatocellular carcinoma development using liver stiffness measurement (FibroScan). Hepatology 3:885–894. https://doi.org/10.1002/hep.24121
doi: 10.1002/hep.24121
Lok AS (2004) Prevention of hepatitis B virus-related hepatocellular carcinoma. Gastroenterology 127:S303-309. https://doi.org/10.1053/j.gastro.2004.09.045
doi: 10.1053/j.gastro.2004.09.045
pubmed: 15508098
European association for the study of lhe liver, european organisation for research and treatment of cancer (2012) EASL-EORTC clinical practice guidelines: management of hepatocellular carcinoma. J Hepatol 56:908–943. https://doi.org/10.1016/j.jhep.2011.12.001
doi: 10.1016/j.jhep.2011.12.001
Befeler AS, Di Bisceglie AM (2002) Hepatocellular carcinoma: diagnosis and treatment. Gastroenterology 122:1609–1619. https://doi.org/10.1053/gast.2002.33411
doi: 10.1053/gast.2002.33411
pubmed: 12016426
Daniele B, Bencivenga A, Megna AS, Tinessa V (2004) Alpha-fetoprotein and ultrasonography screening for hepatocellular carcinoma. Gastroenterology 127:S108-112. https://doi.org/10.1053/j.gastro.2004.09.023
doi: 10.1053/j.gastro.2004.09.023
pubmed: 15508073
Tzartzeva K, Obi J, Rich NE, Parikh ND, Marrero JA, Yopp A, Waljee AK, Singal AG (2018) Surveillance imaging and alpha fetoprotein for early detection of hepatocellular carcinoma in patients with cirrhosis: a meta-analysis. Gastroenterology 154:1706–1718. https://doi.org/10.1053/j.gastro.2018.01.064
doi: 10.1053/j.gastro.2018.01.064
pubmed: 29425931
Johnson CH, Ivanisevic J, Siuzdak G (2016) Metabolomics: beyond biomarkers and towards mechanisms. Nat Rev Mol Cell Biol 17:451–459. https://doi.org/10.1038/nrm.2016.25
doi: 10.1038/nrm.2016.25
pubmed: 26979502
pmcid: 5729912
Gaggini M, Cabiati M, Del Turco S, Navarra T, De Simone P, Filipponi F, Del Ry S, Gastaldelli A, Basta G (2017) Increased FNDC5/Irisin expression in human hepatocellular carcinoma. Peptides 88:62–66. https://doi.org/10.1016/j.peptides.2016.12.014
doi: 10.1016/j.peptides.2016.12.014
pubmed: 28012856
Cabiati M, Gaggini M, Cesare MM, Caselli C, De Simone P, Filipponi F, Basta G, Gastaldelli A, Del Ry S (2017) Osteopontin in hepatocellular carcinoma: a possible biomarker for diagnosis and follow-up. Cytokine 99:59–65. https://doi.org/10.1016/j.cyto.2017.07.004
doi: 10.1016/j.cyto.2017.07.004
pubmed: 28711012
Cabiati M, Gaggini M, De Simone P, Basta G, Gastaldelli A, Del Ry S (2020) Assessment of RANKL/RANK/osteoprotegerin system expression in patients with hepatocellular carcinoma. Minerva Endocrinol 46:367–369. https://doi.org/10.23736/S0391-1977.20.03163-6
doi: 10.23736/S0391-1977.20.03163-6
Cabiati M, Gaggini M, De Simone P, Del Ry S (2021) Evaluation of Apelin/APJ system expression in hepatocellular carcinoma as a function of clinical severity. Clin Exp Med 21:269–275. https://doi.org/10.1007/s10238-020-00672-x
doi: 10.1007/s10238-020-00672-x
pubmed: 33201338
Cabiati M, Gaggini M, De Simone P, Del Ry S (2021) Do pentraxin 3 and neural pentraxin 2 have different facet function in hepatocellular carcinoma? Clin Exp Med 21:555–562. https://doi.org/10.1007/s10238-021-00714-y
doi: 10.1007/s10238-021-00714-y
pubmed: 33905035
Renema N, Navet B, Heymann MF, Lezot F, Heymann D (2016) RANK-RANKL signalling in cancer. Biosci Rep 5:36. https://doi.org/10.1042/BSR20160150
doi: 10.1042/BSR20160150
Cheng ML, Fong L (2014) Effects of RANKL-targeted therapy in immunity and cancer. Front Oncol 3:329. https://doi.org/10.3389/fonc.2013.00329
doi: 10.3389/fonc.2013.00329
pubmed: 24432249
pmcid: 3882875
Santini D, Perrone G, Roato I, Godio L, Pantano F, Grasso D, Russo A, Vincenzi B, Fratto ME, Sabbatini R, Della Pepa C, Porta C, Del Conte A, Schiavon G, Berruti A, Tomasino RM, Papotti M, Papapietro N, Onetti Muda A, Denaro V, Tonini G (2011) Expression pattern of receptor activator of NFkappaB (RANK) in a series of primary solid tumors and related bone metastases. J Cell Physiol 226:780–784. https://doi.org/10.1002/jcp.22402
doi: 10.1002/jcp.22402
pubmed: 20857484
Sasaki A, Ishikawa K, Haraguchi N, Inoue H, Ishio T, Shibata K, Ohta M, Kitano S, Mori M (2007) Receptor activator of nuclear factor-kappaB ligand (RANKL) expression in hepatocellular carcinoma with bone metastasis. Ann Surg Oncol 14:1191–1199. https://doi.org/10.1245/s10434-006-9277-4
doi: 10.1245/s10434-006-9277-4
pubmed: 17195907
von Roemeling CA, Radisky DC, Marlow LA, Cooper SJ, Grebe SK, Anastasiadis PZ, Tun HW, Copland JA (2014) Neuronal pentraxin 2 supports clear cell renal cell carcinoma by activating the AMPA-selective glutamate receptor-4. Cancer Res 74:4796–4810. https://doi.org/10.1158/0008-5472.CAN-14-0210
doi: 10.1158/0008-5472.CAN-14-0210
Song T, Wang C, Guo C, Liu Q, Zheng X (2018) Pentraxin 3 overexpression accelerated tumor metastasis and indicated poor prognosis in hepatocellular carcinoma via driving epithelial-mesenchymal transition. J Cancer 9:2650–2658. https://doi.org/10.7150/jca.25188
doi: 10.7150/jca.25188
pubmed: 30087705
pmcid: 6072810
Elmore S (2007) Apoptosis: a review of programmed cell death. Toxicol Pathol 35:495–516. https://doi.org/10.1080/01926230701320337
doi: 10.1080/01926230701320337
pubmed: 17562483
pmcid: 2117903
Bustin SA, Benes V, Garson JA, Hellemans J, Huggett J, Kubista M, Mueller R, Nolan T, Pfaffl MW, Shipley GL, Vandesompele J, Wittwer CT (2009) The MIQE guidelines: minimum information for publication of quantitative real-time PCR experiments. Clin Chem 55:611–622. https://doi.org/10.1373/clinchem.2008.112797
doi: 10.1373/clinchem.2008.112797
pubmed: 19246619
Warde-Farley D, Donaldson SL, Comes O, Zuberi K, Badrawi R, Chao P, Franz M, Grouios C, Kazi F, Lopes CT, Maitland A, Mostafavi S, Montojo J, Shao Q, Wright G, Bader GD, Morris Q (2010) The GeneMANIA prediction server: biological network integration for gene prioritization and predicting gene function. Nucleic Acids Res 38:W214–W220. https://doi.org/10.1093/nar/gkq537
doi: 10.1093/nar/gkq537
pubmed: 20576703
pmcid: 2896186
Tang Z, Li C, Kang B, Gao G, Li C, Zhang Z (2017) GEPIA: a web server for cancer and normal gene expression profiling and interactive analyses. Nucleic Acids Res 45:W98-102. https://doi.org/10.1093/nar/gkx247
doi: 10.1093/nar/gkx247
pubmed: 28407145
pmcid: 5570223
Lian Q, Wang S, Zhang G, Wang D, Luo G, Tang J, Chen L, Gu J (2018) HCCDB: a database of hepatocellular carcinoma expression atlas. Genomics Proteomics Bioinform 16:269–275. https://doi.org/10.1016/j.gpb.2018.07.003
doi: 10.1016/j.gpb.2018.07.003
Chandrashekar DS, Bashel B, Balasubramanya SAH, Creighton CJ, Rodriguez IP, Chakravarthi BVSK, Varambally S (2017) UALCAN: a portal for facilitating tumor subgroup gene expression and survival analyses. Neoplasia 19:649–658. https://doi.org/10.1016/j.neo.2017.05.002
doi: 10.1016/j.neo.2017.05.002
pubmed: 28732212
pmcid: 5516091
Zucman-Rossi J, Villanueva A, Nault JC, Llovet JM (2015) Genetic landscape and biomarkers of hepatocellular carcinoma. Gastroenterology 149:1226–1239. https://doi.org/10.1053/j.gastro.2015.05.061
doi: 10.1053/j.gastro.2015.05.061
pubmed: 26099527
Allain C, Angenard G, Clement B, Coulouarn C (2016) Integrative genomic analysis identifies the core transcriptional hallmarks of human hepatocellular carcinoma. Cancer Res 76:6374–6381
doi: 10.1158/0008-5472.CAN-16-1559
Yang Y, Chen L, Gu J, Zhang H, Yuan J, Lian Q, Lv G, Wang S, Wu Y, Yang YT, Wang D, Liu Y, Tang J, Luo G, Li Y, Hu L, Sun X, Wang D, Guo M, Xi Q, Xi J, Wang H, Zhang MQ, Lu ZJ (2017) Recurrently deregulated lncRNAs in hepatocellular carcinoma. Nat Commun 8:14421. https://doi.org/10.1038/ncomms14421
doi: 10.1038/ncomms14421
pubmed: 28194035
pmcid: 5316832
Piñero F, Dirchwolf M, Pessôa MG (2020) Biomarkers in hepatocellular carcinoma: diagnosis, prognosis and treatment response assessment. Cells 9:1370. https://doi.org/10.3390/cells9061370
doi: 10.3390/cells9061370
pmcid: 7349517
Planey CR, Gevaert O (2016) CoINcIDE: a framework for discovery of patient subtypes across multiple datasets. Genome Med 8:27. https://doi.org/10.1186/s13073-016-0281-4
doi: 10.1186/s13073-016-0281-4
pubmed: 26961683
pmcid: 4784276
Hoshida Y, Nijman SM, Kobayashi M, Chan JA, Brunet JP, Chiang DY, Villanueva A, Newell P, Ikeda K, Hashimoto M, Watanabe G, Gabriel S, Friedman SL, Kumada H, Llovet JM, Golub TR (2009) Integrative transcriptome analysis reveals common molecular subclasses of human hepatocellular carcinoma. Cancer Res 69:7385–7392. https://doi.org/10.1158/0008-5472.CAN-09-1089
doi: 10.1158/0008-5472.CAN-09-1089
pubmed: 19723656
pmcid: 3549578
Tsuchiya N, Sawada Y, Endo I, Saito K, Uemura Y, Nakatsura T (2015) Biomarkers for the early diagnosis of hepatocellular carcinoma. World J Gastroenterol 21:10573–10583. https://doi.org/10.3748/wjg.v21.i37.10573
doi: 10.3748/wjg.v21.i37.10573
pubmed: 26457017
pmcid: 4588079
Rittling SR, Chambers AF (2004) Role of osteopontin in tumor progression. Br J Cancer 90:1877–1881. https://doi.org/10.1038/sj.bjc.6601839
doi: 10.1038/sj.bjc.6601839
pubmed: 15138464
pmcid: 2410284
Muto J, Shirabe K, Yoshizumi T, Ikegami T, Aishima S, Ishigami K, Yonemitsu Y, Ikeda T, Soejima Y, Maehara Y (2014) The Apelin-APJ system induces tumor arteriogenesis in hepatocellular carcinoma. Anti-cancer Res 34:5313–5320
Masoumi J, Jafarzadeh A, Khorramdelazad H, Abbasloui M, Abdolalizadeh J, Jamali N (2020) Role of Apelin/APJ axis in cancer development and progression. Adv Med Sci 65:202–210. https://doi.org/10.1016/j.advms.2020.02.002
doi: 10.1016/j.advms.2020.02.002
pubmed: 32087570
Kelly PN, Strasser A (2011) The role of Bcl-2 and its pro-survival relatives in tumorigenesis and cancer therapy. Cell Death Differ 18:1414. https://doi.org/10.1038/cdd.2011.17
doi: 10.1038/cdd.2011.17
pubmed: 21415859
pmcid: 3149740
Carmo RF, Aroucha D, Vasconcelos LR, Pereira LM, Moura P, Cavalcanti MS (2016) Genetic variation in PTX3 and plasma levels associated with hepatocellular carcinoma in patients with HCV. J Viral Hepat 23:116–122. https://doi.org/10.1111/jvh.12472
doi: 10.1111/jvh.12472
pubmed: 26400151
Zhang XW, Xu B (2000) Differential regulation of P53, c-Myc, Bcl-2, BAX and AFP protein expression, and caspase activity during 10-hydroxycamptothecin-induced apoptosis in Hep G2 cells. Anticancer Drugs 11:747–756. https://doi.org/10.1097/00001813-200010000-00012
doi: 10.1097/00001813-200010000-00012
pubmed: 11129738
Marquardt JU, Edlich F (2019) Predisposition to apoptosis in hepatocellular carcinoma: from mechanistic insights to therapeutic strategies. Front Oncol 9:1421. https://doi.org/10.3389/fonc.2019.01421
doi: 10.3389/fonc.2019.01421
pubmed: 31921676
pmcid: 6923252
Zhang Y, Wang S, Xiao J, Zhou H (2019) Bioinformatics analysis to identify the key genes affecting the progression and prognosis of hepatocellular carcinoma. Biosci Rep 39:BSR20181845. https://doi.org/10.1042/BSR20181845
doi: 10.1042/BSR20181845
pubmed: 30705088
pmcid: 6386764
Zhu RX, Cheng ASL, Chan HLY, Yang DY, Seto WK (2019) Growth arrest-specific gene 2 suppresses hepatocarcinogenesis by intervention of cell cycle and p53-dependent apoptosis. World J Gastroenterol 25:4715–4726. https://doi.org/10.3748/wjg.v25.i32.4715
doi: 10.3748/wjg.v25.i32.4715
pubmed: 31528096
pmcid: 6718038
Fu PY, Hu B, Ma XL, Yang ZF, Yu MC, Sun HX, Huang A, Zhang X, Wang J, Hu ZQ, Zhou CH, Tang WG, Ning R, Xu Y, Zhou J (2019) New insight into BIRC3: A novel prognostic indicator and a potential therapeutic target for liver cancer. J Cell Biochem 120:6035–6045. https://doi.org/10.1002/jcb.27890
doi: 10.1002/jcb.27890
pubmed: 30368883
Zhang X, Zhang J, Liu Y, Li J, Tan J, Song Z (2021) Bcl-2 associated athanogene 2 (BAG2) is associated with progression and prognosis of hepatocellular carcinoma: a bioinformatics-based analysis. Pathol Oncol Res 27:594649. https://doi.org/10.3389/pore.2021.594649
doi: 10.3389/pore.2021.594649
pubmed: 34257542
pmcid: 8262200
Wang T, Xie X, Liu H, Chen F, Du J, Wang X, Jiang X, Yu F, Fan H (2019) Pyridine nucleotide-disulphide oxidoreductase domain 2 (PYROXD2): role in mitochondrial function. Mitochondrion 47:114–124. https://doi.org/10.1016/j.mito.2019.05.007
doi: 10.1016/j.mito.2019.05.007
pubmed: 31170524
Chao T, Shih HT, Hsu SC, Chen PJ, Fan YS, Jeng YM, Shen ZQ, Tsai TF, Chang ZF (2021) Autophagy restricts mitochondrial DNA damage-induced release of ENDOG (endonuclease G) to regulate genome stability. Autophagy 17:3444–3460. https://doi.org/10.1080/15548627.2021.1874209
doi: 10.1080/15548627.2021.1874209
pubmed: 33465003
pmcid: 8632313
Liu D, Liu M, Wang W, Pang L, Wang Z, Yuan C, Liu K (2018) Overexpression of apoptosis-inducing factor mitochondrion-associated 1 (AIFM1) induces apoptosis by promoting the transcription of caspase3 and DRAM in hepatoma cells. Biochem Biophys Res Commun 498:453–457. https://doi.org/10.1016/j.bbrc.2018.02.203
doi: 10.1016/j.bbrc.2018.02.203
pubmed: 29501488
Guo D, Li YR, Chen DF, Wang RH, Zhang D, Zhu M, He SX, Lu XL (2021) Regulatory effects of LIM kinase 1 on the proliferation and metastasis of hepatocellular carcinoma cells. Zhonghua Gan Zang Bing Za Zhi 29:427–432. https://doi.org/10.3760/cma.j.cn501113-20191113-00419
doi: 10.3760/cma.j.cn501113-20191113-00419
pubmed: 34107579