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Transcriptomic and immunohistochemical approaches identify HLA-G as a predictive biomarker of gestational choriocarcinoma resistance to monochemotherapy
Using a transcriptional approach on tissue samples, we sought to identify predictive biomarkers of post molar malignant transformation, and of choriocarcinoma chemosensitivity to mono- (methotrexate or actinomycin D) or polychemotherapy [EMA(Etoposide, Methotrexate, Actinomycin D)-CO(Cyclophosphamid...
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| Published in: | Gynecologic oncology 2020-09, Vol.158 (3), p.785-793 |
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| creator | Bolze, Pierre-Adrien Lopez, Jonathan Allias, Fabienne Hajri, Touria Patrier, Sophie Devouassoux-Shisheboran, Mojgan Massardier, Jérôme You, Benoit Golfier, François Mallet, François |
| description | Using a transcriptional approach on tissue samples, we sought to identify predictive biomarkers of post molar malignant transformation, and of choriocarcinoma chemosensitivity to mono- (methotrexate or actinomycin D) or polychemotherapy [EMA(Etoposide, Methotrexate, Actinomycin D)-CO(Cyclophosphamide, Vincristine) and EMA-EP(Etoposide, Cisplatine)] regimens.
We studied the expression of a 760-gene panel (PanCancer Pathway) related to oncogenesis and immune tolerance in tissue samples of complete hydatidiform moles and gestational choriocarcinoma.
We did not identify any differentially expressed gene between moles with post molar malignant transformation in choriocarcinoma (n = 14) and moles with remission (n = 20). In monochemoresistant choriocarcinoma (n = 34), four genes (HLA-G, COL27A1, IL1R2 and GLI3) had a significantly reduced expression and one (THEM4) had an increased expression [FDR (false discovery rate) adjusted p-value ≤ 0.05] when compared to monochemosensitive choriocarcinoma (n = 9). The proportion of trophoblast cells and the intensity of immunohistochemical HLA-G expression were reduced in monochemoresistant choriocarcinoma (p |
| doi_str_mv | 10.1016/j.ygyno.2020.05.042 |
| format | article |
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We studied the expression of a 760-gene panel (PanCancer Pathway) related to oncogenesis and immune tolerance in tissue samples of complete hydatidiform moles and gestational choriocarcinoma.
We did not identify any differentially expressed gene between moles with post molar malignant transformation in choriocarcinoma (n = 14) and moles with remission (n = 20). In monochemoresistant choriocarcinoma (n = 34), four genes (HLA-G, COL27A1, IL1R2 and GLI3) had a significantly reduced expression and one (THEM4) had an increased expression [FDR (false discovery rate) adjusted p-value ≤ 0.05] when compared to monochemosensitive choriocarcinoma (n = 9). The proportion of trophoblast cells and the intensity of immunohistochemical HLA-G expression were reduced in monochemoresistant choriocarcinoma (p < 0.05). In polychemoresistant choriocarcinoma (n = 20) we did not identify differentially expressed genes with an FDR adjusted p-value ≤ 0.05 when compared to polychemosensitive choriocarcinoma (n = 15). Gene pathway analysis revealed a predicted activation of IFN ᵞ in monochemoresistant choriocarcinoma and inhibited IL2 and TNF in polychemoresistant choriocarcinoma. The main biological functions predicted to be altered in chemoresistant choriocarcinoma were related to immunological homeostasis and leukopoiesis.
HLA-G is a strong candidate gene to predict choriocarcinoma resistance to monochemotherapy and that further studies are required to implement its routine quantification in the decision process for the management of gestational choriocarcinoma.
•Moles with post-curettage choriocarcinoma evolution and those with remission show similar transcriptomic profiles.•HLA-G is under-expressed in monochemotherapy resistant gestational choriocarcinoma.•Polychemosensitive and polychemoresistant choriocarcinoma show similar transcriptomic profiles.</description><identifier>ISSN: 0090-8258</identifier><identifier>EISSN: 1095-6859</identifier><identifier>DOI: 10.1016/j.ygyno.2020.05.042</identifier><identifier>PMID: 32513563</identifier><language>eng</language><publisher>United States: Elsevier Inc</publisher><subject>Adult ; Antineoplastic Agents - administration & dosage ; Antineoplastic Agents - pharmacology ; Antineoplastic Combined Chemotherapy Protocols - administration & dosage ; Antineoplastic Combined Chemotherapy Protocols - pharmacology ; Biomarkers, Tumor - genetics ; Biomarkers, Tumor - metabolism ; Chemoresistance ; Choriocarcinoma - drug therapy ; Choriocarcinoma - genetics ; Choriocarcinoma - metabolism ; Drug Resistance, Neoplasm ; Female ; Gestational choriocarcinoma ; Gestational trophoblastic neoplasia ; HLA-G ; HLA-G Antigens - genetics ; HLA-G Antigens - metabolism ; Humans ; Hydatidiform Mole - drug therapy ; Hydatidiform Mole - genetics ; Hydatidiform Mole - metabolism ; Hydatidiform moles ; Immunohistochemistry ; Life Sciences ; Methotrexate ; Middle Aged ; Predictive Value of Tests ; Pregnancy ; Transcriptome ; Uterine Neoplasms - drug therapy ; Uterine Neoplasms - genetics ; Young Adult</subject><ispartof>Gynecologic oncology, 2020-09, Vol.158 (3), p.785-793</ispartof><rights>2020 Elsevier Inc.</rights><rights>Copyright © 2020 Elsevier Inc. All rights reserved.</rights><rights>Attribution - NonCommercial</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c438t-a127a9ba2ca93b7e7630fcdd261f34b769f8310f18f71ab994822a05d9afae823</citedby><cites>FETCH-LOGICAL-c438t-a127a9ba2ca93b7e7630fcdd261f34b769f8310f18f71ab994822a05d9afae823</cites><orcidid>0000-0003-3768-2378 ; 0000-0002-1331-096X ; 0000-0002-4988-9723</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>230,314,776,780,881,27901,27902</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/32513563$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink><backlink>$$Uhttps://hal.science/hal-03492199$$DView record in HAL$$Hfree_for_read</backlink></links><search><creatorcontrib>Bolze, Pierre-Adrien</creatorcontrib><creatorcontrib>Lopez, Jonathan</creatorcontrib><creatorcontrib>Allias, Fabienne</creatorcontrib><creatorcontrib>Hajri, Touria</creatorcontrib><creatorcontrib>Patrier, Sophie</creatorcontrib><creatorcontrib>Devouassoux-Shisheboran, Mojgan</creatorcontrib><creatorcontrib>Massardier, Jérôme</creatorcontrib><creatorcontrib>You, Benoit</creatorcontrib><creatorcontrib>Golfier, François</creatorcontrib><creatorcontrib>Mallet, François</creatorcontrib><title>Transcriptomic and immunohistochemical approaches identify HLA-G as a predictive biomarker of gestational choriocarcinoma resistance to monochemotherapy</title><title>Gynecologic oncology</title><addtitle>Gynecol Oncol</addtitle><description>Using a transcriptional approach on tissue samples, we sought to identify predictive biomarkers of post molar malignant transformation, and of choriocarcinoma chemosensitivity to mono- (methotrexate or actinomycin D) or polychemotherapy [EMA(Etoposide, Methotrexate, Actinomycin D)-CO(Cyclophosphamide, Vincristine) and EMA-EP(Etoposide, Cisplatine)] regimens.
We studied the expression of a 760-gene panel (PanCancer Pathway) related to oncogenesis and immune tolerance in tissue samples of complete hydatidiform moles and gestational choriocarcinoma.
We did not identify any differentially expressed gene between moles with post molar malignant transformation in choriocarcinoma (n = 14) and moles with remission (n = 20). In monochemoresistant choriocarcinoma (n = 34), four genes (HLA-G, COL27A1, IL1R2 and GLI3) had a significantly reduced expression and one (THEM4) had an increased expression [FDR (false discovery rate) adjusted p-value ≤ 0.05] when compared to monochemosensitive choriocarcinoma (n = 9). The proportion of trophoblast cells and the intensity of immunohistochemical HLA-G expression were reduced in monochemoresistant choriocarcinoma (p < 0.05). In polychemoresistant choriocarcinoma (n = 20) we did not identify differentially expressed genes with an FDR adjusted p-value ≤ 0.05 when compared to polychemosensitive choriocarcinoma (n = 15). Gene pathway analysis revealed a predicted activation of IFN ᵞ in monochemoresistant choriocarcinoma and inhibited IL2 and TNF in polychemoresistant choriocarcinoma. The main biological functions predicted to be altered in chemoresistant choriocarcinoma were related to immunological homeostasis and leukopoiesis.
HLA-G is a strong candidate gene to predict choriocarcinoma resistance to monochemotherapy and that further studies are required to implement its routine quantification in the decision process for the management of gestational choriocarcinoma.
•Moles with post-curettage choriocarcinoma evolution and those with remission show similar transcriptomic profiles.•HLA-G is under-expressed in monochemotherapy resistant gestational choriocarcinoma.•Polychemosensitive and polychemoresistant choriocarcinoma show similar transcriptomic profiles.</description><subject>Adult</subject><subject>Antineoplastic Agents - administration & dosage</subject><subject>Antineoplastic Agents - pharmacology</subject><subject>Antineoplastic Combined Chemotherapy Protocols - administration & dosage</subject><subject>Antineoplastic Combined Chemotherapy Protocols - pharmacology</subject><subject>Biomarkers, Tumor - genetics</subject><subject>Biomarkers, Tumor - metabolism</subject><subject>Chemoresistance</subject><subject>Choriocarcinoma - drug therapy</subject><subject>Choriocarcinoma - genetics</subject><subject>Choriocarcinoma - metabolism</subject><subject>Drug Resistance, Neoplasm</subject><subject>Female</subject><subject>Gestational choriocarcinoma</subject><subject>Gestational trophoblastic neoplasia</subject><subject>HLA-G</subject><subject>HLA-G Antigens - genetics</subject><subject>HLA-G Antigens - metabolism</subject><subject>Humans</subject><subject>Hydatidiform Mole - drug therapy</subject><subject>Hydatidiform Mole - genetics</subject><subject>Hydatidiform Mole - metabolism</subject><subject>Hydatidiform moles</subject><subject>Immunohistochemistry</subject><subject>Life Sciences</subject><subject>Methotrexate</subject><subject>Middle Aged</subject><subject>Predictive Value of Tests</subject><subject>Pregnancy</subject><subject>Transcriptome</subject><subject>Uterine Neoplasms - drug therapy</subject><subject>Uterine Neoplasms - genetics</subject><subject>Young Adult</subject><issn>0090-8258</issn><issn>1095-6859</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2020</creationdate><recordtype>article</recordtype><recordid>eNp9kc2O0zAUhS0EYkrhCZCQl7BIuLbz5wWLagRTpEpshrV14zgTl8QOdlopb8Lj4k6HWbKyfPXdc-xzCHnPIGfAqs_HfH1Ync85cMihzKHgL8iGgSyzqinlS7IBkJA1vGxuyJsYjwAggPHX5EbwkomyEhvy5z6gizrYefGT1RRdR-00nZwfbFy8Hkya4khxnoPHdI3UdsYttl_p_rDL7ihGinQOprN6sWdDW-snDL9MoL6nDyYuuFjvkoQefLBeY9DWJYQGE5MFOm3o4unk3aObXwYTcF7fklc9jtG8ezq35Oe3r_e3--zw4-777e6Q6UI0S4aM1yhb5BqlaGtTVwJ63XW8Yr0o2rqSfSMY9Kzpa4atlEXDOULZSezRNFxsyaer7oCjmoNNb1-VR6v2u4O6zEAUkjMpzyyxH69syuL3KX1NTTZqM47ojD9FxQvGGFQsJbsl4orq4GMMpn_WZqAu9amjeqxPXepTUKpUX9r68GRwaifTPe_86ysBX66ASZGcrQkqamtShJ0NRi-q8_a_Bn8B92mwhg</recordid><startdate>20200901</startdate><enddate>20200901</enddate><creator>Bolze, Pierre-Adrien</creator><creator>Lopez, Jonathan</creator><creator>Allias, Fabienne</creator><creator>Hajri, Touria</creator><creator>Patrier, Sophie</creator><creator>Devouassoux-Shisheboran, Mojgan</creator><creator>Massardier, Jérôme</creator><creator>You, Benoit</creator><creator>Golfier, François</creator><creator>Mallet, François</creator><general>Elsevier Inc</general><general>Elsevier</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope><scope>1XC</scope><scope>VOOES</scope><orcidid>https://orcid.org/0000-0003-3768-2378</orcidid><orcidid>https://orcid.org/0000-0002-1331-096X</orcidid><orcidid>https://orcid.org/0000-0002-4988-9723</orcidid></search><sort><creationdate>20200901</creationdate><title>Transcriptomic and immunohistochemical approaches identify HLA-G as a predictive biomarker of gestational choriocarcinoma resistance to monochemotherapy</title><author>Bolze, Pierre-Adrien ; Lopez, Jonathan ; Allias, Fabienne ; Hajri, Touria ; Patrier, Sophie ; Devouassoux-Shisheboran, Mojgan ; Massardier, Jérôme ; You, Benoit ; Golfier, François ; Mallet, François</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c438t-a127a9ba2ca93b7e7630fcdd261f34b769f8310f18f71ab994822a05d9afae823</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2020</creationdate><topic>Adult</topic><topic>Antineoplastic Agents - administration & dosage</topic><topic>Antineoplastic Agents - pharmacology</topic><topic>Antineoplastic Combined Chemotherapy Protocols - administration & dosage</topic><topic>Antineoplastic Combined Chemotherapy Protocols - pharmacology</topic><topic>Biomarkers, Tumor - genetics</topic><topic>Biomarkers, Tumor - metabolism</topic><topic>Chemoresistance</topic><topic>Choriocarcinoma - drug therapy</topic><topic>Choriocarcinoma - genetics</topic><topic>Choriocarcinoma - metabolism</topic><topic>Drug Resistance, Neoplasm</topic><topic>Female</topic><topic>Gestational choriocarcinoma</topic><topic>Gestational trophoblastic neoplasia</topic><topic>HLA-G</topic><topic>HLA-G Antigens - genetics</topic><topic>HLA-G Antigens - metabolism</topic><topic>Humans</topic><topic>Hydatidiform Mole - drug therapy</topic><topic>Hydatidiform Mole - genetics</topic><topic>Hydatidiform Mole - metabolism</topic><topic>Hydatidiform moles</topic><topic>Immunohistochemistry</topic><topic>Life Sciences</topic><topic>Methotrexate</topic><topic>Middle Aged</topic><topic>Predictive Value of Tests</topic><topic>Pregnancy</topic><topic>Transcriptome</topic><topic>Uterine Neoplasms - drug therapy</topic><topic>Uterine Neoplasms - genetics</topic><topic>Young Adult</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Bolze, Pierre-Adrien</creatorcontrib><creatorcontrib>Lopez, Jonathan</creatorcontrib><creatorcontrib>Allias, Fabienne</creatorcontrib><creatorcontrib>Hajri, Touria</creatorcontrib><creatorcontrib>Patrier, Sophie</creatorcontrib><creatorcontrib>Devouassoux-Shisheboran, Mojgan</creatorcontrib><creatorcontrib>Massardier, Jérôme</creatorcontrib><creatorcontrib>You, Benoit</creatorcontrib><creatorcontrib>Golfier, François</creatorcontrib><creatorcontrib>Mallet, François</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><collection>Hyper Article en Ligne (HAL)</collection><collection>Hyper Article en Ligne (HAL) (Open Access)</collection><jtitle>Gynecologic oncology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Bolze, Pierre-Adrien</au><au>Lopez, Jonathan</au><au>Allias, Fabienne</au><au>Hajri, Touria</au><au>Patrier, Sophie</au><au>Devouassoux-Shisheboran, Mojgan</au><au>Massardier, Jérôme</au><au>You, Benoit</au><au>Golfier, François</au><au>Mallet, François</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Transcriptomic and immunohistochemical approaches identify HLA-G as a predictive biomarker of gestational choriocarcinoma resistance to monochemotherapy</atitle><jtitle>Gynecologic oncology</jtitle><addtitle>Gynecol Oncol</addtitle><date>2020-09-01</date><risdate>2020</risdate><volume>158</volume><issue>3</issue><spage>785</spage><epage>793</epage><pages>785-793</pages><issn>0090-8258</issn><eissn>1095-6859</eissn><abstract>Using a transcriptional approach on tissue samples, we sought to identify predictive biomarkers of post molar malignant transformation, and of choriocarcinoma chemosensitivity to mono- (methotrexate or actinomycin D) or polychemotherapy [EMA(Etoposide, Methotrexate, Actinomycin D)-CO(Cyclophosphamide, Vincristine) and EMA-EP(Etoposide, Cisplatine)] regimens.
We studied the expression of a 760-gene panel (PanCancer Pathway) related to oncogenesis and immune tolerance in tissue samples of complete hydatidiform moles and gestational choriocarcinoma.
We did not identify any differentially expressed gene between moles with post molar malignant transformation in choriocarcinoma (n = 14) and moles with remission (n = 20). In monochemoresistant choriocarcinoma (n = 34), four genes (HLA-G, COL27A1, IL1R2 and GLI3) had a significantly reduced expression and one (THEM4) had an increased expression [FDR (false discovery rate) adjusted p-value ≤ 0.05] when compared to monochemosensitive choriocarcinoma (n = 9). The proportion of trophoblast cells and the intensity of immunohistochemical HLA-G expression were reduced in monochemoresistant choriocarcinoma (p < 0.05). In polychemoresistant choriocarcinoma (n = 20) we did not identify differentially expressed genes with an FDR adjusted p-value ≤ 0.05 when compared to polychemosensitive choriocarcinoma (n = 15). Gene pathway analysis revealed a predicted activation of IFN ᵞ in monochemoresistant choriocarcinoma and inhibited IL2 and TNF in polychemoresistant choriocarcinoma. The main biological functions predicted to be altered in chemoresistant choriocarcinoma were related to immunological homeostasis and leukopoiesis.
HLA-G is a strong candidate gene to predict choriocarcinoma resistance to monochemotherapy and that further studies are required to implement its routine quantification in the decision process for the management of gestational choriocarcinoma.
•Moles with post-curettage choriocarcinoma evolution and those with remission show similar transcriptomic profiles.•HLA-G is under-expressed in monochemotherapy resistant gestational choriocarcinoma.•Polychemosensitive and polychemoresistant choriocarcinoma show similar transcriptomic profiles.</abstract><cop>United States</cop><pub>Elsevier Inc</pub><pmid>32513563</pmid><doi>10.1016/j.ygyno.2020.05.042</doi><tpages>9</tpages><orcidid>https://orcid.org/0000-0003-3768-2378</orcidid><orcidid>https://orcid.org/0000-0002-1331-096X</orcidid><orcidid>https://orcid.org/0000-0002-4988-9723</orcidid><oa>free_for_read</oa></addata></record> |
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| ispartof | Gynecologic oncology, 2020-09, Vol.158 (3), p.785-793 |
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| subjects | Adult Antineoplastic Agents - administration & dosage Antineoplastic Agents - pharmacology Antineoplastic Combined Chemotherapy Protocols - administration & dosage Antineoplastic Combined Chemotherapy Protocols - pharmacology Biomarkers, Tumor - genetics Biomarkers, Tumor - metabolism Chemoresistance Choriocarcinoma - drug therapy Choriocarcinoma - genetics Choriocarcinoma - metabolism Drug Resistance, Neoplasm Female Gestational choriocarcinoma Gestational trophoblastic neoplasia HLA-G HLA-G Antigens - genetics HLA-G Antigens - metabolism Humans Hydatidiform Mole - drug therapy Hydatidiform Mole - genetics Hydatidiform Mole - metabolism Hydatidiform moles Immunohistochemistry Life Sciences Methotrexate Middle Aged Predictive Value of Tests Pregnancy Transcriptome Uterine Neoplasms - drug therapy Uterine Neoplasms - genetics Young Adult |
| title | Transcriptomic and immunohistochemical approaches identify HLA-G as a predictive biomarker of gestational choriocarcinoma resistance to monochemotherapy |
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