Transcriptomic characterization of cancer-testis antigens identifies MAGEA3 as a driver of tumor progression in hepatocellular carcinoma.
Journal
PLoS genetics
ISSN: 1553-7404
Titre abrégé: PLoS Genet
Pays: United States
ID NLM: 101239074
Informations de publication
Date de publication:
06 2021
06 2021
Historique:
received:
02
07
2020
accepted:
07
05
2021
entrez:
24
6
2021
pubmed:
25
6
2021
medline:
28
10
2021
Statut:
epublish
Résumé
Cancer testis antigens (CTAs) are an extensive gene family with a unique expression pattern restricted to germ cells, but aberrantly reactivated in cancer tissues. Studies indicate that the expression (or re-expression) of CTAs within the MAGE-A family is common in hepatocellular carcinoma (HCC). However, no systematic characterization has yet been reported. The aim of this study is to perform a comprehensive profile of CTA de-regulation in HCC and experimentally evaluate the role of MAGEA3 as a driver of HCC progression. The transcriptomic analysis of 44 multi-regionally sampled HCCs from 12 patients identified high intra-tumor heterogeneity of CTAs. In addition, a subset of CTAs was significantly overexpressed in histologically poorly differentiated regions. Further analysis of CTAs in larger patient cohorts revealed high CTA expression related to worse overall survival and several other markers of poor prognosis. Functional analysis of MAGEA3 was performed in human HCC cell lines by gene silencing and in a genetic mouse model by overexpression of MAGEA3 in the liver. Knockdown of MAGEA3 decreased cell proliferation, colony formation and increased apoptosis. MAGEA3 overexpression was associated with more aggressive tumors in vivo. In conclusion MAGEA3 enhances tumor progression and should be considered as a novel therapeutic target in HCC.
Identifiants
pubmed: 34166362
doi: 10.1371/journal.pgen.1009589
pii: PGENETICS-D-20-01038
pmc: PMC8224860
doi:
Substances chimiques
Antigens, Neoplasm
0
MAGEA3 protein, human
0
Neoplasm Proteins
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.
Langues
eng
Sous-ensembles de citation
IM
Pagination
e1009589Subventions
Organisme : Cancer Research UK
ID : 26813
Pays : United Kingdom
Organisme : NCI NIH HHS
ID : P30 CA196521
Pays : United States
Organisme : NCI NIH HHS
ID : R37 CA230636
Pays : United States
Déclaration de conflit d'intérêts
I have read the journal’s policy and the authors of this manuscript have the following competing interests: AL has received grant support from Pfizer and Genentech, and lecture fees from Exelixis for unrelated projects. MRdG has received grant support from Genentech for unrelated projects. AV has received consulting fees from Guidepoint and Fujifilm; advisory board fees from Exact Sciences, Nucleix and NGM Pharmaceuticals. JML has received grant support from Bayer HealthCare Pharmaceuticals, Eisai Inc, Bristol-Myers Squibb, Boehringer-Ingelheim and Ipsen and consulting fees from Bayer HealthCare Pharmaceuticals, Merck, Eisai Inc, Bristol-Myers Squibb, Celsion Corporation, Eli Lilly, Roche, Genentech, Glycotest, Nucleix, Can-Fite Biopharma, AstraZeneca, and Exelixis.
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