Identification and Characterization of Copy Number-Associated Driver Genes in Esophageal Squamous Cell Carcinoma.
Carcinogenesis
/ genetics
Cell Cycle
/ genetics
DNA Copy Number Variations
/ genetics
Esophageal Neoplasms
/ genetics
Esophageal Squamous Cell Carcinoma
/ genetics
Gene Dosage
/ genetics
Gene Expression Profiling
/ methods
Gene Expression Regulation, Neoplastic
/ genetics
Humans
Oncogenes
/ genetics
Prognosis
Signal Transduction
/ genetics
Transcription Factors
/ genetics
Journal
BioMed research international
ISSN: 2314-6141
Titre abrégé: Biomed Res Int
Pays: United States
ID NLM: 101600173
Informations de publication
Date de publication:
2020
2020
Historique:
received:
15
06
2020
accepted:
17
07
2020
entrez:
10
9
2020
pubmed:
11
9
2020
medline:
28
4
2021
Statut:
epublish
Résumé
Esophageal squamous cell carcinoma (ESCC) is a leading malignancy with both high incidence and mortality worldwide. However, the molecular mechanisms of the poor prognosis in ESCC are still unclear. We conducted differential expression analysis between ESCC and normal tissues and between ESCC samples with and without CNAs in a given gene. Overrepresentation enrichment and gene set enrichment analyses were used to identify the oncogenic pathways and abnormal transcription factors (TFs). The survival analysis was employed to identify the genes associated with overall survival. In this study, we aimed to identify and interpret the driver genes triggered by the copy number alterations (CNAs), including CCND1, TEAD4, EIF4EBP1, EGFR, FGFR3, and FZD6. Furthermore, we identified oncogenic pathways, including RTK-RAS, WNT, PI3K, Hippo, and cell cycle, and key TFs including TEAD4, a transcription factor in the Hippo signaling pathway, and LEF1 in the WNT signaling pathway. Furthermore, we observed that upregulations of FGFR3 and EIF4EBP1 were significantly associated with shorter overall survival in ESCC. In conclusion, the driver genes triggered by CNAs not only exhibited critical functionality but also were clinically relevant in ESCC, which greatly improved our understanding of the molecular mechanisms in ESCC.
Sections du résumé
BACKGROUND
BACKGROUND
Esophageal squamous cell carcinoma (ESCC) is a leading malignancy with both high incidence and mortality worldwide. However, the molecular mechanisms of the poor prognosis in ESCC are still unclear.
METHODS
METHODS
We conducted differential expression analysis between ESCC and normal tissues and between ESCC samples with and without CNAs in a given gene. Overrepresentation enrichment and gene set enrichment analyses were used to identify the oncogenic pathways and abnormal transcription factors (TFs). The survival analysis was employed to identify the genes associated with overall survival.
RESULTS
RESULTS
In this study, we aimed to identify and interpret the driver genes triggered by the copy number alterations (CNAs), including CCND1, TEAD4, EIF4EBP1, EGFR, FGFR3, and FZD6. Furthermore, we identified oncogenic pathways, including RTK-RAS, WNT, PI3K, Hippo, and cell cycle, and key TFs including TEAD4, a transcription factor in the Hippo signaling pathway, and LEF1 in the WNT signaling pathway. Furthermore, we observed that upregulations of FGFR3 and EIF4EBP1 were significantly associated with shorter overall survival in ESCC.
CONCLUSION
CONCLUSIONS
In conclusion, the driver genes triggered by CNAs not only exhibited critical functionality but also were clinically relevant in ESCC, which greatly improved our understanding of the molecular mechanisms in ESCC.
Identifiants
pubmed: 32908901
doi: 10.1155/2020/6387519
pmc: PMC7463369
doi:
Substances chimiques
Transcription Factors
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
6387519Informations de copyright
Copyright © 2020 Kexin Jiang et al.
Déclaration de conflit d'intérêts
All authors claimed no competing conflicts of interest.
Références
Int J Mol Sci. 2016 Jan 21;17(1):
pubmed: 26805820
Onco Targets Ther. 2018 Nov 15;11:8165-8173
pubmed: 30532557
Virchows Arch. 2011 Feb;458(2):171-8
pubmed: 21046149
OMICS. 2012 May;16(5):284-7
pubmed: 22455463
Biochim Biophys Acta Proteins Proteom. 2020 Aug;1868(8):140444
pubmed: 32423886
Oncologist. 2020 Jun;25(6):e881-e886
pubmed: 32323889
J Biol Chem. 2007 Dec 14;282(50):36571-81
pubmed: 17951630
Nat Genet. 2014 Oct;46(10):1097-102
pubmed: 25151357
Proc Natl Acad Sci U S A. 1998 Aug 18;95(17):10164-9
pubmed: 9707618
Nat Genet. 2014 May;46(5):467-73
pubmed: 24686850
Oncotarget. 2015 Feb 10;6(4):2562-72
pubmed: 25537505
Gut. 2010 Nov;59(11):1457-64
pubmed: 20833657
Ann Oncol. 2014 Sep;25(9):1769-74
pubmed: 24907633
World J Gastroenterol. 2013 Sep 14;19(34):5598-606
pubmed: 24039351
BMC Cancer. 2019 May 23;19(1):491
pubmed: 31122207
Oncol Lett. 2018 Jun;15(6):8983-8990
pubmed: 29844815
Cancer. 1994 Sep 15;74(6):1686-92
pubmed: 8082069
Cell Death Dis. 2019 Aug 9;10(8):603
pubmed: 31399556
Nature. 2017 Jan 12;541(7636):169-175
pubmed: 28052061
Nat Rev Dis Primers. 2017 Jul 27;3:17048
pubmed: 28748917
Nat Genet. 2016 Oct;48(10):1131-41
pubmed: 27595477
Am J Hum Genet. 2015 Apr 2;96(4):597-611
pubmed: 25839328
J Histochem Cytochem. 2016 Jan;64(1):7-17
pubmed: 26487184
Ann Oncol. 2018 Apr 1;29(4):938-944
pubmed: 29351612
Lancet. 2013 Feb 2;381(9864):400-12
pubmed: 23374478
Genome Res. 2012 Sep;22(9):1760-74
pubmed: 22955987
Clin Transl Oncol. 2020 Jul;22(7):1172-1179
pubmed: 31748958
World J Gastroenterol. 2016 Feb 21;22(7):2284-93
pubmed: 26900290
CA Cancer J Clin. 2018 Nov;68(6):394-424
pubmed: 30207593
Cancer Med. 2018 Aug;7(8):3977-3987
pubmed: 29974668
Nat Rev Cancer. 2011 Jul 07;11(8):558-72
pubmed: 21734724
Cell. 2018 Apr 5;173(2):321-337.e10
pubmed: 29625050
J Surg Oncol. 2012 Mar;105(3):288-92
pubmed: 21932407