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Transcriptomic characterization of cancer-testis antigens identifies MAGEA3 as a driver of tumor progression in hepatocellular carcinoma.
Craig, Amanda J; Garcia-Lezana, Teresa; Ruiz de Galarreta, Marina; Villacorta-Martin, Carlos; Kozlova, Edgar G; Martins-Filho, Sebastiao N; von Felden, Johann; Ahsen, Mehmet Eren; Bresnahan, Erin; Hernandez-Meza, Gabriela; Labgaa, Ismail; D'Avola, Delia; Schwartz, Myron; Llovet, Josep M; Sia, Daniela; Thung, Swan; Losic, Bojan; Lujambio, Amaia; Villanueva, Augusto.
Afiliación
  • Craig AJ; Division of Liver Diseases, Department of Medicine, Liver Cancer Program, Tisch Cancer Institute, Graduate School of Biomedical Sciences, Icahn School of Medicine at Mount Sinai, New York City, New York, United States of America.
  • Garcia-Lezana T; Division of Liver Diseases, Department of Medicine, Liver Cancer Program, Tisch Cancer Institute, Graduate School of Biomedical Sciences, Icahn School of Medicine at Mount Sinai, New York City, New York, United States of America.
  • Ruiz de Galarreta M; Division of Liver Diseases, Department of Medicine, Liver Cancer Program, Tisch Cancer Institute, Graduate School of Biomedical Sciences, Icahn School of Medicine at Mount Sinai, New York City, New York, United States of America.
  • Villacorta-Martin C; Department of Oncological Sciences, The Tisch Cancer Institute, Graduate School of Biomedical Sciences, Icahn School of Medicine at Mount Sinai, New York City, New York, United States of America.
  • Kozlova EG; Precision Immunology Institute at Icahn School of Medicine at Mount Sinai, New York City, New York, United States of America.
  • Martins-Filho SN; Division of Liver Diseases, Department of Medicine, Liver Cancer Program, Tisch Cancer Institute, Graduate School of Biomedical Sciences, Icahn School of Medicine at Mount Sinai, New York City, New York, United States of America.
  • von Felden J; Department of Genetics and Genomic Sciences, Cancer Immunology Program, Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York City, New York, United States of America.
  • Ahsen ME; Icahn Institute for Data Science and Genomic Technology, Icahn School of Medicine at Mount Sinai, New York City, New York, United States of America.
  • Bresnahan E; Division of Liver Diseases, Department of Medicine, Liver Cancer Program, Tisch Cancer Institute, Graduate School of Biomedical Sciences, Icahn School of Medicine at Mount Sinai, New York City, New York, United States of America.
  • Hernandez-Meza G; Department of Laboratory Medicine and Pathobiology, University Health Network, University of Toronto, Toronto, Canada.
  • Labgaa I; Division of Liver Diseases, Department of Medicine, Liver Cancer Program, Tisch Cancer Institute, Graduate School of Biomedical Sciences, Icahn School of Medicine at Mount Sinai, New York City, New York, United States of America.
  • D'Avola D; Department of Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
  • Schwartz M; Department of Genetics and Genomic Sciences, Cancer Immunology Program, Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York City, New York, United States of America.
  • Llovet JM; Division of Liver Diseases, Department of Medicine, Liver Cancer Program, Tisch Cancer Institute, Graduate School of Biomedical Sciences, Icahn School of Medicine at Mount Sinai, New York City, New York, United States of America.
  • Sia D; Department of Oncological Sciences, The Tisch Cancer Institute, Graduate School of Biomedical Sciences, Icahn School of Medicine at Mount Sinai, New York City, New York, United States of America.
  • Thung S; Precision Immunology Institute at Icahn School of Medicine at Mount Sinai, New York City, New York, United States of America.
  • Losic B; Division of Liver Diseases, Department of Medicine, Liver Cancer Program, Tisch Cancer Institute, Graduate School of Biomedical Sciences, Icahn School of Medicine at Mount Sinai, New York City, New York, United States of America.
  • Lujambio A; Division of Liver Diseases, Department of Medicine, Liver Cancer Program, Tisch Cancer Institute, Graduate School of Biomedical Sciences, Icahn School of Medicine at Mount Sinai, New York City, New York, United States of America.
  • Villanueva A; Department of Visceral Surgery, Lausanne University Hospital CHUV, Lausanne, Switzerland.
PLoS Genet ; 17(6): e1009589, 2021 06.
Article en En | MEDLINE | ID: mdl-34166362
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.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Testículo / Carcinoma Hepatocelular / Transcriptoma / Neoplasias Hepáticas / Antígenos de Neoplasias / Proteínas de Neoplasias Tipo de estudio: Prognostic_studies Límite: Humans / Male Idioma: En Revista: PLoS Genet Asunto de la revista: GENETICA Año: 2021 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Testículo / Carcinoma Hepatocelular / Transcriptoma / Neoplasias Hepáticas / Antígenos de Neoplasias / Proteínas de Neoplasias Tipo de estudio: Prognostic_studies Límite: Humans / Male Idioma: En Revista: PLoS Genet Asunto de la revista: GENETICA Año: 2021 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos