Integrated Genomic and Transcriptomic Analysis reveals key genes for predicting dual-phenotype Hepatocellular Carcinoma Prognosis.
CXCL9
RNA sequencing
dual-phenotype hepatocellular carcinoma
prognosis
whole exome sequencing
Journal
Journal of Cancer
ISSN: 1837-9664
Titre abrégé: J Cancer
Pays: Australia
ID NLM: 101535920
Informations de publication
Date de publication:
2021
2021
Historique:
received:
16
11
2020
accepted:
20
02
2021
entrez:
15
4
2021
pubmed:
16
4
2021
medline:
16
4
2021
Statut:
epublish
Résumé
Dual-phenotype hepatocellular carcinoma (DPHCC) expresses both hepatocyte and cholangiocyte markers, and is characterized by high recurrence and low survival rates. The underlying molecular mechanisms of DPHCC pathogenesis are unclear. We performed whole exome sequencing and RNA sequencing of three subtypes of HCC (10 DPHCC, 10 CK19-positive HCC, and 14 CK19-negative HCC), followed by integrated bioinformatics analysis, including somatic mutation analysis, mutation signal analysis, differential gene expression analysis, and pathway enrichment analysis. Cox proportional hazard regression analyses were applied for exploring survival related characteristics. We found that mutated genes in DPHCC patients were associated with carcinogenesis and immunity, and the up-regulated genes were mainly enriched in transcription-related and cancer-related pathways, and the down-regulated genes were mainly enriched in immune-related pathways. CXCL9 was selected as the hub gene, which is associated with immune cells and survival prognosis. Our results showed that low CXCL9 expression was significantly associated with poor prognosis, and its expression was significantly reduced in DPHCC samples. In conclusion, we explored the molecular mechanisms governing DPHCC development and progression and identified CXCL9, which influences the immune microenvironment and prognosis of DPHCC and might be new clinically significant biomarkers for predicting prognosis.
Identifiants
pubmed: 33854600
doi: 10.7150/jca.56005
pii: jcav12p2993
pmc: PMC8040886
doi:
Types de publication
Journal Article
Langues
eng
Pagination
2993-3010Informations de copyright
© The author(s).
Déclaration de conflit d'intérêts
Competing Interests: The authors have declared that no competing interest exists.
Références
Nucleic Acids Res. 2006 Jul 1;34(Web Server issue):W720-4
pubmed: 16845106
J Cell Sci. 2016 Jan 1;129(1):9-16
pubmed: 26729027
Gastroenterology. 2010 Apr;138(4):1429-40
pubmed: 19909745
Bioinformatics. 2011 Feb 1;27(3):431-2
pubmed: 21149340
Ann N Y Acad Sci. 2011 Jan;1217:1-17
pubmed: 21155837
Histopathology. 2020 Jan;76(2):182-188
pubmed: 31433515
Toxicon. 2017 Dec 15;140:60-71
pubmed: 29031804
Cell. 2006 Nov 17;127(4):775-88
pubmed: 17110336
Cancer Sci. 2020 Feb;111(2):323-333
pubmed: 31799781
Cancer Med. 2016 Nov;5(11):3246-3259
pubmed: 27726306
Biomed Pharmacother. 2016 Mar;78:8-13
pubmed: 26898419
PLoS One. 2016 Dec 9;11(12):e0167455
pubmed: 27935967
Novartis Found Symp. 2002;247:91-101; discussion 101-3, 119-28, 244-52
pubmed: 12539951
BMC Syst Biol. 2014;8 Suppl 4:S11
pubmed: 25521941
BMC Biol. 2019 Jun 10;17(1):46
pubmed: 31182083
Hepatology. 2009 Jan;49(1):318-29
pubmed: 19111019
Nat Rev Gastroenterol Hepatol. 2014 Jun;11(6):340-9
pubmed: 24473361
Cancer Med. 2019 May;8(5):2338-2347
pubmed: 30884206
Nature. 2016 Oct 13;538(7624):260-264
pubmed: 27698416
Cancer Res. 2017 Nov 1;77(21):e108-e110
pubmed: 29092952
Cell. 2011 Mar 4;144(5):646-74
pubmed: 21376230
Dig Dis. 2014;32(6):778-85
pubmed: 25376296
J Immunol. 2007 Feb 15;178(4):2278-86
pubmed: 17277133
Nat Biotechnol. 2013 Mar;31(3):213-9
pubmed: 23396013
Sci Rep. 2018 Jul 11;8(1):10461
pubmed: 29992971
Life Sci. 2019 Feb 1;218:197-204
pubmed: 30582951
J Clin Oncol. 2010 Jan 1;28(1):105-13
pubmed: 19917869
Sci Immunol. 2019 Mar 15;4(33):
pubmed: 30877143
PLoS One. 2017 Jan 23;12(1):e0170465
pubmed: 28114366
Genome Biol. 2014;15(12):550
pubmed: 25516281
J Biol Chem. 2013 Jan 4;288(1):123-31
pubmed: 23105102
Oncology. 2017;92 Suppl 1:40-49
pubmed: 27764823
Cell Death Dis. 2018 Feb 15;9(3):271
pubmed: 29449544
Tumour Biol. 2015 Mar;36(3):1849-57
pubmed: 25409614
Medicine (Baltimore). 2015 Mar;94(12):e659
pubmed: 25816035
Science. 2013 Mar 29;339(6127):1546-58
pubmed: 23539594
Nat Genet. 2011 Aug 07;43(9):828-9
pubmed: 21822264
Mol Cancer. 2018 May 26;17(1):93
pubmed: 29803224
Nat Biotechnol. 2019 Aug;37(8):907-915
pubmed: 31375807
BMC Genomics. 2013 Mar 14;14:172
pubmed: 23497092
Trends Genet. 2015 Apr;31(4):208-14
pubmed: 25733351
Nature. 1982 Dec 23;300(5894):765-7
pubmed: 6960256
Cold Spring Harb Perspect Med. 2015 Jul 17;5(9):a021535
pubmed: 26187874
Transfusion. 2015 Dec;55(12):2778-82
pubmed: 26545564
Bioinformatics. 2015 Nov 15;31(22):3673-5
pubmed: 26163694
Oncogene. 2000 Jan 13;19(2):188-99
pubmed: 10644996
Mol Cancer Res. 2019 Jan;17(1):177-185
pubmed: 30166312
EMBO J. 2001 Nov 15;20(22):6404-13
pubmed: 11707411
Virchows Arch. 2015 May;466(5):541-8
pubmed: 25742908
World J Gastroenterol. 2012 Sep 14;18(34):4751-7
pubmed: 23002345
Nucleic Acids Res. 2013 Jan;41(Database issue):D808-15
pubmed: 23203871
Histopathology. 2008 Jan;52(2):224-32
pubmed: 18184271
Nat Genet. 2000 May;25(1):25-9
pubmed: 10802651
World J Surg. 2017 Mar;41(3):825-834
pubmed: 27812807
EMBO J. 1987 Dec 20;6(13):4073-81
pubmed: 2965007
Comput Biol Chem. 2018 Aug;75:54-64
pubmed: 29747076
Genome Biol. 2014 Sep 25;15(9):473
pubmed: 25253082
Nat Genet. 2015 Dec;47(12):1402-7
pubmed: 26551669
Genome Biol. 2003;4(5):P3
pubmed: 12734009
Mol Clin Oncol. 2018 Dec;9(6):597-606
pubmed: 30546887
Br J Cancer. 2016 Aug 23;115(5):553-63
pubmed: 27490802
Ann Surg Oncol. 2011 Aug;18(8):2210-7
pubmed: 21308485
Breast Cancer. 2018 Mar;25(2):206-212
pubmed: 29139094
Nucleic Acids Res. 2010 Sep;38(16):e164
pubmed: 20601685
Nat Med. 2011 Mar;17(3):297-303
pubmed: 21383744
PLoS Comput Biol. 2016 Apr 21;12(4):e1004873
pubmed: 27100738
Cancer Sci. 2018 May;109(5):1282-1291
pubmed: 29573058
Nat Biotechnol. 2015 Mar;33(3):290-5
pubmed: 25690850
Mol Cell Proteomics. 2014 Oct;13(10):2661-72
pubmed: 25034945
Gastroenterology. 2015 Oct;149(5):1226-1239.e4
pubmed: 26099527
Am J Surg. 2005 Jan;189(1):120-5
pubmed: 15701504
Transplantation. 2006 Dec 27;82(12):1712-9
pubmed: 17198265
Cell. 2016 Mar 10;164(6):1233-1247
pubmed: 26967289
Nature. 2020 Feb;578(7793):94-101
pubmed: 32025018
J Pathol. 1999 Dec;189(4):552-8
pubmed: 10629557
Cancer Cell. 2019 Jun 10;35(6):885-900.e10
pubmed: 31185212
Am Stat. 2011;65(4):213-221
pubmed: 22690019
Cancer Manag Res. 2019 Mar 29;11:2531-2543
pubmed: 31114322
Cancer Lett. 2009 Dec 28;286(2):145-53
pubmed: 19464789
Tumour Biol. 2017 Mar;39(3):1010428317695971
pubmed: 28347229
Cancer Cell. 2017 Jun 12;31(6):820-832.e3
pubmed: 28528867
Circ Cardiovasc Qual Outcomes. 2011 May;4(3):363-71
pubmed: 21586725
Genome Res. 2013 Sep;23(9):1422-33
pubmed: 23788652
J Anim Sci Biotechnol. 2019 Jun 21;10:44
pubmed: 31249686
Am J Pathol. 2018 Feb;188(2):378-391
pubmed: 29174628
Eur J Med Chem. 2016 Feb 15;109:314-41
pubmed: 26807863
Mol Med Rep. 2018 May;17(5):7017-7026
pubmed: 29568863
Clin Exp Immunol. 2006 Sep;145(3):535-44
pubmed: 16907924
J Immunol. 2006 Feb 1;176(3):1456-64
pubmed: 16424173
Nucleic Acids Res. 2017 Jan 4;45(D1):D777-D783
pubmed: 27899578
Breast Cancer Res. 2014 Sep 28;16(5):449
pubmed: 25260534
Genome Med. 2018 Apr 25;10(1):33
pubmed: 29695279
Nat Genet. 2015 May;47(5):505-511
pubmed: 25822088
World J Gastroenterol. 2016 Nov 14;22(42):9279-9287
pubmed: 27895416
J Cancer Res Ther. 2018 Oct-Dec;14(6):1239-1244
pubmed: 30488837
Nature. 2001 Nov 1;414(6859):105-11
pubmed: 11689955
Clin Rev Allergy Immunol. 2018 Apr;54(2):282-294
pubmed: 29256057
PLoS One. 2017 Jan 5;12(1):e0169605
pubmed: 28056073
Nat Med. 2015 Aug;21(8):846-53
pubmed: 26248267
Cell Death Dis. 2018 Jul 23;9(8):802
pubmed: 30038287
J Hepatol. 2018 Oct;69(4):840-850
pubmed: 29958939
Nat Genet. 2012 May 27;44(7):760-4
pubmed: 22634756
Genome Biol. 2016 Aug 22;17(1):174
pubmed: 27549193
Sci Rep. 2017 Aug 2;7(1):7106
pubmed: 28769055
Mol Med Rep. 2017 Oct;16(4):5561-5567
pubmed: 28849002
Front Pharmacol. 2018 Jun 21;9:657
pubmed: 29977206
J Pathol Transl Med. 2016 Jan;50(1):52-7
pubmed: 26581206
BMC Cancer. 2016 Nov 18;16(1):903
pubmed: 27863477
J Cancer. 2020 Mar 5;11(11):3400-3406
pubmed: 32231746
CA Cancer J Clin. 2018 Nov;68(6):394-424
pubmed: 30207593
Hepatology. 2011 Nov;54(5):1707-17
pubmed: 22045674
Am J Pathol. 1949 Jul;25(4):647-55
pubmed: 18152860
J Exp Clin Cancer Res. 2018 Sep 19;37(1):231
pubmed: 30231922
Cytokine Growth Factor Rev. 2013 Feb;24(1):41-9
pubmed: 22989616
Genome Biol. 2016 Feb 22;17:31
pubmed: 26899170
Ann Surg Oncol. 2013 Dec;20 Suppl 3:S616-24
pubmed: 23838921
Proc Natl Acad Sci U S A. 2010 Jun 15;107(24):10920-5
pubmed: 20534451
J Registry Manag. 2011 Winter;38(4):201-5
pubmed: 23270094
Cell Stem Cell. 2015 Apr 2;16(4):413-25
pubmed: 25842979
BMC Cancer. 2015 Apr 09;15:242
pubmed: 25886454
Nature. 2012 Jan 18;481(7381):306-13
pubmed: 22258609
J Hepatol. 2013 Nov;59(5):1107-17
pubmed: 23835194
Oncol Rep. 2017 Oct;38(4):2351-2359
pubmed: 28849121
J Biol Chem. 2007 Mar 23;282(12):8812-20
pubmed: 17272277