Open AccessTranscriptomic characterization of cancer-testis antigens identifies MAGEA3 as a driver of tumor progression in hepatocellular carcinoma
Author(s) -
Amanda Craig,
Teresa GarcíaLezana,
Marina Ruiz de Galarreta,
Carlos Villacorta-Martín,
Edgar Kozlova,
Sebastião N. Martins-Filho,
Johann von Felden,
Mehmet Eren Ahsen,
Erin Bresnahan,
Gabriela Hernandez-Meza,
Ismaïl Labgaa,
Delia D’Avola,
Myron Schwartz,
Josep M. Llovet,
Daniela Sia,
Swan N. Thung,
Bojan Losic,
Amaia Lujambio,
Augusto Villanueva
Publication year - 2021
Publication title -
plos genetics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.587
H-Index - 233
eISSN - 1553-7404
pISSN - 1553-7390
DOI - 10.1371/journal.pgen.1009589
Subject(s) - biology , cancer research , hccs , transcriptome , carcinogenesis , liver cancer , cancer , gene knockdown , hepatocellular carcinoma , gene silencing , gene expression , genetics , cell culture , gene
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.