@article{
 title = {Identification of an Immune-specific Class of Hepatocellular Carcinoma, Based on Molecular Features},
 type = {article},
 year = {2017},
 identifiers = {[object Object]},
 pages = {812-826},
 volume = {153},
 websites = {https://www.sciencedirect.com/science/article/pii/S0016508517357414},
 month = {9},
 publisher = {W.B. Saunders},
 day = {1},
 id = {2e1ec1a2-4b24-3b25-a339-250cec5282c1},
 created = {2018-08-15T00:11:58.904Z},
 accessed = {2018-08-14},
 file_attached = {true},
 profile_id = {b63e8b24-ed73-38a0-835d-fc93fa76b2df},
 group_id = {7cefe685-317a-3d95-8344-b52e9a2517ff},
 last_modified = {2018-10-25T21:47:38.406Z},
 read = {false},
 starred = {false},
 authored = {false},
 confirmed = {false},
 hidden = {false},
 citation_key = {Sia2017},
 private_publication = {false},
 abstract = {BACKGROUND & AIMS
Agents that induce an immune response against tumors by altering T-cell regulation have increased survival times of patients with advanced-stage tumors, such as melanoma or lung cancer. We aimed to characterize molecular features of immune cells that infiltrate hepatocellular carcinomas (HCCs) to determine whether these types of agents might be effective against liver tumors. 

METHODS
We analyzed HCC samples from 956 patients. We separated gene expression profiles from tumor, stromal, and immune cells using a non-negative matrix factorization algorithm. We then analyzed the gene expression pattern of inflammatory cells in HCC tumor samples. We correlated expression patterns with the presence of immune cell infiltrates and immune regulatory molecules, determined by pathology and immunohistochemical analyses, in a training set of 228 HCC samples. We validated the correlation in a validation set of 728 tumor samples. Using data from 190 tumors in the Cancer Genome Atlas, we correlated immune cell gene expression profiles with numbers of chromosomal aberrations (based on single-nucleotide polymorphism array) and mutations (exome sequence data). 

RESULTS
We found approximately 25% of HCCs to have markers of an inflammatory response, with high expression levels of the CD274 molecule (programmed death-ligand 1) and programmed cell death 1, markers of cytolytic activity, and fewer chromosomal aberrations. We called this group of tumors the Immune class. It contained 2 subtypes, characterized by markers of an adaptive T-cell response or exhausted immune response. The exhausted immune response subclass expressed many genes regulated by transforming growth factor beta 1 that mediate immunosuppression. We did not observe any differences in numbers of mutations or expression of tumor antigens between the immune-specific class and other HCCs. 

CONCLUSIONS
In an analysis of HCC samples from 956 patients, we found almost 25% to express markers of an inflammatory response. We identified 2 subclasses, characterized by adaptive or exhausted immune responses. These findings indicate that some HCCs might be susceptible to therapeutic agents designed to block the regulatory pathways in T cells, such as programmed death-ligand 1, programmed cell death 1, or transforming growth factor beta 1 inhibitors.},
 bibtype = {article},
 author = {Sia, Daniela and Jiao, Yang and Martinez-Quetglas, Iris and Kuchuk, Olga and Villacorta-Martin, Carlos and Castro de Moura, Manuel and Putra, Juan and Camprecios, Genis and Bassaganyas, Laia and Akers, Nicholas and Losic, Bojan and Waxman, Samuel and Thung, Swan N. and Mazzaferro, Vincenzo and Esteller, Manel and Friedman, Scott L. and Schwartz, Myron and Villanueva, Augusto and Llovet, Josep M.},
 journal = {Gastroenterology},
 number = {3}
}

{"_id":"ir7YGK92YMdt9XPPR","bibbaseid":"sia-jiao-martinezquetglas-kuchuk-villacortamartin-castrodemoura-putra-camprecios-etal-identificationofanimmunespecificclassofhepatocellularcarcinomabasedonmolecularfeatures-2017","downloads":0,"creationDate":"2019-03-08T20:39:38.730Z","title":"Identification of an Immune-specific Class of Hepatocellular Carcinoma, Based on Molecular Features","author_short":["Sia, D.","Jiao, Y.","Martinez-Quetglas, I.","Kuchuk, O.","Villacorta-Martin, C.","Castro de Moura, M.","Putra, J.","Camprecios, G.","Bassaganyas, L.","Akers, N.","Losic, B.","Waxman, S.","Thung, S., N.","Mazzaferro, V.","Esteller, M.","Friedman, S., L.","Schwartz, M.","Villanueva, A.","Llovet, J., M."],"year":2017,"bibtype":"article","biburl":null,"bibdata":{"title":"Identification of an Immune-specific Class of Hepatocellular Carcinoma, Based on Molecular Features","type":"article","year":"2017","identifiers":"[object Object]","pages":"812-826","volume":"153","websites":"https://www.sciencedirect.com/science/article/pii/S0016508517357414","month":"9","publisher":"W.B. Saunders","day":"1","id":"2e1ec1a2-4b24-3b25-a339-250cec5282c1","created":"2018-08-15T00:11:58.904Z","accessed":"2018-08-14","file_attached":"true","profile_id":"b63e8b24-ed73-38a0-835d-fc93fa76b2df","group_id":"7cefe685-317a-3d95-8344-b52e9a2517ff","last_modified":"2018-10-25T21:47:38.406Z","read":false,"starred":false,"authored":false,"confirmed":false,"hidden":false,"citation_key":"Sia2017","private_publication":false,"abstract":"BACKGROUND & AIMS\nAgents that induce an immune response against tumors by altering T-cell regulation have increased survival times of patients with advanced-stage tumors, such as melanoma or lung cancer. We aimed to characterize molecular features of immune cells that infiltrate hepatocellular carcinomas (HCCs) to determine whether these types of agents might be effective against liver tumors. \n\nMETHODS\nWe analyzed HCC samples from 956 patients. We separated gene expression profiles from tumor, stromal, and immune cells using a non-negative matrix factorization algorithm. We then analyzed the gene expression pattern of inflammatory cells in HCC tumor samples. We correlated expression patterns with the presence of immune cell infiltrates and immune regulatory molecules, determined by pathology and immunohistochemical analyses, in a training set of 228 HCC samples. We validated the correlation in a validation set of 728 tumor samples. Using data from 190 tumors in the Cancer Genome Atlas, we correlated immune cell gene expression profiles with numbers of chromosomal aberrations (based on single-nucleotide polymorphism array) and mutations (exome sequence data). \n\nRESULTS\nWe found approximately 25% of HCCs to have markers of an inflammatory response, with high expression levels of the CD274 molecule (programmed death-ligand 1) and programmed cell death 1, markers of cytolytic activity, and fewer chromosomal aberrations. We called this group of tumors the Immune class. It contained 2 subtypes, characterized by markers of an adaptive T-cell response or exhausted immune response. The exhausted immune response subclass expressed many genes regulated by transforming growth factor beta 1 that mediate immunosuppression. We did not observe any differences in numbers of mutations or expression of tumor antigens between the immune-specific class and other HCCs. \n\nCONCLUSIONS\nIn an analysis of HCC samples from 956 patients, we found almost 25% to express markers of an inflammatory response. We identified 2 subclasses, characterized by adaptive or exhausted immune responses. These findings indicate that some HCCs might be susceptible to therapeutic agents designed to block the regulatory pathways in T cells, such as programmed death-ligand 1, programmed cell death 1, or transforming growth factor beta 1 inhibitors.","bibtype":"article","author":"Sia, Daniela and Jiao, Yang and Martinez-Quetglas, Iris and Kuchuk, Olga and Villacorta-Martin, Carlos and Castro de Moura, Manuel and Putra, Juan and Camprecios, Genis and Bassaganyas, Laia and Akers, Nicholas and Losic, Bojan and Waxman, Samuel and Thung, Swan N. and Mazzaferro, Vincenzo and Esteller, Manel and Friedman, Scott L. and Schwartz, Myron and Villanueva, Augusto and Llovet, Josep M.","journal":"Gastroenterology","number":"3","bibtex":"@article{\n title = {Identification of an Immune-specific Class of Hepatocellular Carcinoma, Based on Molecular Features},\n type = {article},\n year = {2017},\n identifiers = {[object Object]},\n pages = {812-826},\n volume = {153},\n websites = {https://www.sciencedirect.com/science/article/pii/S0016508517357414},\n month = {9},\n publisher = {W.B. Saunders},\n day = {1},\n id = {2e1ec1a2-4b24-3b25-a339-250cec5282c1},\n created = {2018-08-15T00:11:58.904Z},\n accessed = {2018-08-14},\n file_attached = {true},\n profile_id = {b63e8b24-ed73-38a0-835d-fc93fa76b2df},\n group_id = {7cefe685-317a-3d95-8344-b52e9a2517ff},\n last_modified = {2018-10-25T21:47:38.406Z},\n read = {false},\n starred = {false},\n authored = {false},\n confirmed = {false},\n hidden = {false},\n citation_key = {Sia2017},\n private_publication = {false},\n abstract = {BACKGROUND & AIMS\nAgents that induce an immune response against tumors by altering T-cell regulation have increased survival times of patients with advanced-stage tumors, such as melanoma or lung cancer. We aimed to characterize molecular features of immune cells that infiltrate hepatocellular carcinomas (HCCs) to determine whether these types of agents might be effective against liver tumors. \n\nMETHODS\nWe analyzed HCC samples from 956 patients. We separated gene expression profiles from tumor, stromal, and immune cells using a non-negative matrix factorization algorithm. We then analyzed the gene expression pattern of inflammatory cells in HCC tumor samples. We correlated expression patterns with the presence of immune cell infiltrates and immune regulatory molecules, determined by pathology and immunohistochemical analyses, in a training set of 228 HCC samples. We validated the correlation in a validation set of 728 tumor samples. Using data from 190 tumors in the Cancer Genome Atlas, we correlated immune cell gene expression profiles with numbers of chromosomal aberrations (based on single-nucleotide polymorphism array) and mutations (exome sequence data). \n\nRESULTS\nWe found approximately 25% of HCCs to have markers of an inflammatory response, with high expression levels of the CD274 molecule (programmed death-ligand 1) and programmed cell death 1, markers of cytolytic activity, and fewer chromosomal aberrations. We called this group of tumors the Immune class. It contained 2 subtypes, characterized by markers of an adaptive T-cell response or exhausted immune response. The exhausted immune response subclass expressed many genes regulated by transforming growth factor beta 1 that mediate immunosuppression. We did not observe any differences in numbers of mutations or expression of tumor antigens between the immune-specific class and other HCCs. \n\nCONCLUSIONS\nIn an analysis of HCC samples from 956 patients, we found almost 25% to express markers of an inflammatory response. We identified 2 subclasses, characterized by adaptive or exhausted immune responses. These findings indicate that some HCCs might be susceptible to therapeutic agents designed to block the regulatory pathways in T cells, such as programmed death-ligand 1, programmed cell death 1, or transforming growth factor beta 1 inhibitors.},\n bibtype = {article},\n author = {Sia, Daniela and Jiao, Yang and Martinez-Quetglas, Iris and Kuchuk, Olga and Villacorta-Martin, Carlos and Castro de Moura, Manuel and Putra, Juan and Camprecios, Genis and Bassaganyas, Laia and Akers, Nicholas and Losic, Bojan and Waxman, Samuel and Thung, Swan N. and Mazzaferro, Vincenzo and Esteller, Manel and Friedman, Scott L. and Schwartz, Myron and Villanueva, Augusto and Llovet, Josep M.},\n journal = {Gastroenterology},\n number = {3}\n}","author_short":["Sia, D.","Jiao, Y.","Martinez-Quetglas, I.","Kuchuk, O.","Villacorta-Martin, C.","Castro de Moura, M.","Putra, J.","Camprecios, G.","Bassaganyas, L.","Akers, N.","Losic, B.","Waxman, S.","Thung, S., N.","Mazzaferro, V.","Esteller, M.","Friedman, S., L.","Schwartz, M.","Villanueva, A.","Llovet, J., M."],"urls":{"Paper":"https://bibbase.org/service/mendeley/b63e8b24-ed73-38a0-835d-fc93fa76b2df/file/16790cf0-af30-1d4b-34a4-d4c8aaf8b730/2017-Identification_of_an_Immune-specific_Class_of_Hepatocellular_Carcinoma_Based_on_Molecular_Features.pdf.pdf","Website":"https://www.sciencedirect.com/science/article/pii/S0016508517357414"},"bibbaseid":"sia-jiao-martinezquetglas-kuchuk-villacortamartin-castrodemoura-putra-camprecios-etal-identificationofanimmunespecificclassofhepatocellularcarcinomabasedonmolecularfeatures-2017","role":"author","downloads":0,"html":""},"search_terms":["identification","immune","specific","class","hepatocellular","carcinoma","based","molecular","features","sia","jiao","martinez-quetglas","kuchuk","villacorta-martin","castro de moura","putra","camprecios","bassaganyas","akers","losic","waxman","thung","mazzaferro","esteller","friedman","schwartz","villanueva","llovet"],"keywords":[],"authorIDs":[]}