Transcriptomic characterization of cancer-testis antigens identifies MAGEA3 as a driver of tumor progression in hepatocellular carcinoma
Abstract
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.
Document Details
- Document Type
- Pub Defense Publication
- Publication Date
- Jun 24, 2021
- Source ID
- 10.1371/journal.pgen.1009589
Entities
People
- Amaia Lujambio
- Amanda J. Craig
- Augusto Villanueva
- Bojan Losic
- Carlos Villacorta-Martín
- Daniela Sia
- Delia D'Avola
- Edgar Gonzalez‐Kozlova
- Erin Bresnahan
- Gabriela Hernandez-Meza
- Ismail Labgaa
- Johann von Felden
- Josep M. Llovet
- Marina Ruiz de Galarreta
- Mehmet Eren Ahsen
- Myron Schwartz
- Sebastiao N Martins-Filho
- Swan Thung
- Teresa Garcia-Lezana
Organizations
- Asociación Española para el Estudio del Hígado
- Damon Runyon Cancer Research Foundation
- EIT Health
- Foundation for the National Institutes of Health
- Framework Programmes for Research and Technological Development
- Fundación Alfonso Martín Escudero
- Generalitat of Catalonia
- German Research Foundation
- Icahn School of Medicine at Mount Sinai
- National Institutes of Health
- Samuel Waxman Cancer Research Foundation
- Swiss National Science Foundation
- United States Department of Defense