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Transcriptomic characterization of cancer-testis antigens identifies MAGEA3 as a driver of tumor progression in hepatocellular carcinoma

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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.

In: PLOS GENET, Vol. 17, No. 6, e1009589, 06.2021.

Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review

Harvard

Craig, AJ, Garcia-Lezana, T, Ruiz de Galarreta, M, Villacorta-Martin, C, Kozlova, EG, Martins-Filho, SN, von Felden, J, Ahsen, ME, Bresnahan, E, Hernandez-Meza, G, Labgaa, I, D'Avola, D, Schwartz, M, Llovet, JM, Sia, D, Thung, S, Losic, B, Lujambio, A & Villanueva, A 2021, 'Transcriptomic characterization of cancer-testis antigens identifies MAGEA3 as a driver of tumor progression in hepatocellular carcinoma', PLOS GENET, vol. 17, no. 6, e1009589. https://doi.org/10.1371/journal.pgen.1009589

APA

Craig, A. J., Garcia-Lezana, T., Ruiz de Galarreta, M., Villacorta-Martin, C., Kozlova, E. G., Martins-Filho, S. N., von Felden, J., Ahsen, M. E., Bresnahan, E., Hernandez-Meza, G., Labgaa, I., D'Avola, D., Schwartz, M., Llovet, J. M., Sia, D., Thung, S., Losic, B., Lujambio, A., & Villanueva, A. (2021). Transcriptomic characterization of cancer-testis antigens identifies MAGEA3 as a driver of tumor progression in hepatocellular carcinoma. PLOS GENET, 17(6), [e1009589]. https://doi.org/10.1371/journal.pgen.1009589

Vancouver

Craig AJ, Garcia-Lezana T, Ruiz de Galarreta M, Villacorta-Martin C, Kozlova EG, Martins-Filho SN et al. Transcriptomic characterization of cancer-testis antigens identifies MAGEA3 as a driver of tumor progression in hepatocellular carcinoma. PLOS GENET. 2021 Jun;17(6). e1009589. https://doi.org/10.1371/journal.pgen.1009589

Bibtex

@article{17bcc247863a4421857519e9650b201a,
title = "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.",
author = "Craig, {Amanda J} and Teresa Garcia-Lezana and {Ruiz de Galarreta}, Marina and Carlos Villacorta-Martin and Kozlova, {Edgar G} and Martins-Filho, {Sebastiao N} and {von Felden}, Johann and Ahsen, {Mehmet Eren} and Erin Bresnahan and Gabriela Hernandez-Meza and Ismail Labgaa and Delia D'Avola and Myron Schwartz and Llovet, {Josep M} and Daniela Sia and Swan Thung and Bojan Losic and Amaia Lujambio and Augusto Villanueva",
year = "2021",
month = jun,
doi = "10.1371/journal.pgen.1009589",
language = "English",
volume = "17",
journal = "PLOS GENET",
issn = "1553-7404",
publisher = "Public Library of Science",
number = "6",

}

RIS

TY - JOUR

T1 - Transcriptomic characterization of cancer-testis antigens identifies MAGEA3 as a driver of tumor progression in hepatocellular carcinoma

AU - Craig, Amanda J

AU - Garcia-Lezana, Teresa

AU - Ruiz de Galarreta, Marina

AU - Villacorta-Martin, Carlos

AU - Kozlova, Edgar G

AU - Martins-Filho, Sebastiao N

AU - von Felden, Johann

AU - Ahsen, Mehmet Eren

AU - Bresnahan, Erin

AU - Hernandez-Meza, Gabriela

AU - Labgaa, Ismail

AU - D'Avola, Delia

AU - Schwartz, Myron

AU - Llovet, Josep M

AU - Sia, Daniela

AU - Thung, Swan

AU - Losic, Bojan

AU - Lujambio, Amaia

AU - Villanueva, Augusto

PY - 2021/6

Y1 - 2021/6

N2 - 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.

AB - 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.

U2 - 10.1371/journal.pgen.1009589

DO - 10.1371/journal.pgen.1009589

M3 - SCORING: Journal article

C2 - 34166362

VL - 17

JO - PLOS GENET

JF - PLOS GENET

SN - 1553-7404

IS - 6

M1 - e1009589

ER -