Resistance to platinum-based chemotherapy is associated with epithelial to mesenchymal transition in epithelial ovarian cancer
Abstract Background The present study is aimed to identify genetic pathways correlated with chemoresistance in epithelial ovarian cancer (EOC). Methods We compared the molecular profiles of 23 tumour biopsies of stage III–IV (training set) at primary surgery, before chemotherapy, to the profile from...
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| Veröffentlicht in: | European journal of cancer (1990) 2013-01, Vol.49 (2), p.520-530 |
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| container_title | European journal of cancer (1990) |
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| creator | Marchini, Sergio Fruscio, Robert Clivio, Luca Beltrame, Luca Porcu, Luca Nerini, Ilaria Fuso Cavalieri, Duccio Chiorino, Giovanna Cattoretti, Giorgio Mangioni, Costantino Milani, Rodolfo Torri, Valter Romualdi, Chiara Zambelli, Alberto Romano, Michela Signorelli, Mauro Giandomenico, Silvana di D’Incalci, Maurizio |
| description | Abstract Background The present study is aimed to identify genetic pathways correlated with chemoresistance in epithelial ovarian cancer (EOC). Methods We compared the molecular profiles of 23 tumour biopsies of stage III–IV (training set) at primary surgery, before chemotherapy, to the profile from the same patients at second surgery, after several lines of platinum (Pt)-based chemotherapy when the tumours were resistant. In the hypothesis that identified markers were related to Pt-resistance and to prognosis, we validated this signature in 52 EOC taken at primary surgery (validation set) selected to be either very sensitive to the first line therapy, i.e. not relapsing before one year from the end of therapy, or resistant, i.e. relapsing within 6 months from the end of therapy. Results In the training set, we identified a resistance signature indicative of the activation of epithelial to mesenchymal transition (EMT) by transforming growth factor (TGF)-beta pathway. We then validated this signature in 52 EOC taken at primary surgery (validation set). Some genes involved in EMT, such as B MP and a ctivin m embrane- b ound i nhibitor (BAMBI), and mir-141 resulted in association with overall or progression free survival. Conclusion Some genes involved in EMT were associated to overall or progression free survival, suggesting EMT as vital to the resistance mechanisms. |
| doi_str_mv | 10.1016/j.ejca.2012.06.026 |
| format | Article |
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Methods We compared the molecular profiles of 23 tumour biopsies of stage III–IV (training set) at primary surgery, before chemotherapy, to the profile from the same patients at second surgery, after several lines of platinum (Pt)-based chemotherapy when the tumours were resistant. In the hypothesis that identified markers were related to Pt-resistance and to prognosis, we validated this signature in 52 EOC taken at primary surgery (validation set) selected to be either very sensitive to the first line therapy, i.e. not relapsing before one year from the end of therapy, or resistant, i.e. relapsing within 6 months from the end of therapy. Results In the training set, we identified a resistance signature indicative of the activation of epithelial to mesenchymal transition (EMT) by transforming growth factor (TGF)-beta pathway. We then validated this signature in 52 EOC taken at primary surgery (validation set). Some genes involved in EMT, such as B MP and a ctivin m embrane- b ound i nhibitor (BAMBI), and mir-141 resulted in association with overall or progression free survival. Conclusion Some genes involved in EMT were associated to overall or progression free survival, suggesting EMT as vital to the resistance mechanisms.</description><identifier>ISSN: 0959-8049</identifier><identifier>EISSN: 1879-0852</identifier><identifier>DOI: 10.1016/j.ejca.2012.06.026</identifier><identifier>PMID: 22897840</identifier><language>eng</language><publisher>Kidlington: Elsevier Ltd</publisher><subject>Adult ; Aged ; Antineoplastic Combined Chemotherapy Protocols - therapeutic use ; Biological and medical sciences ; Biopsy ; Carcinoma, Ovarian Epithelial ; Disease-Free Survival ; Drug Resistance, Neoplasm ; Epithelial ovarian cancer ; Epithelial to mesenchymal transition ; Epithelial-Mesenchymal Transition - genetics ; Female ; Hematology, Oncology and Palliative Medicine ; Humans ; Medical sciences ; Middle Aged ; Neoplasm Staging ; Neoplasms, Glandular and Epithelial - drug therapy ; Neoplasms, Glandular and Epithelial - genetics ; Neoplasms, Glandular and Epithelial - pathology ; Organoplatinum Compounds - administration & dosage ; Ovarian Neoplasms - drug therapy ; Ovarian Neoplasms - genetics ; Ovarian Neoplasms - pathology ; Pharmacology. Drug treatments ; Platinum-resistance ; Signal Transduction ; Treatment Outcome ; Tumors</subject><ispartof>European journal of cancer (1990), 2013-01, Vol.49 (2), p.520-530</ispartof><rights>Elsevier Ltd</rights><rights>2012 Elsevier Ltd</rights><rights>2014 INIST-CNRS</rights><rights>Copyright © 2012 Elsevier Ltd. All rights reserved.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c441t-5d96abb0227eac462538553c0b8699ee43d8af06092f8214d5a029783f800dca3</citedby><cites>FETCH-LOGICAL-c441t-5d96abb0227eac462538553c0b8699ee43d8af06092f8214d5a029783f800dca3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.sciencedirect.com/science/article/pii/S095980491200562X$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,776,780,3537,27901,27902,65306</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=26849542$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/22897840$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Marchini, Sergio</creatorcontrib><creatorcontrib>Fruscio, Robert</creatorcontrib><creatorcontrib>Clivio, Luca</creatorcontrib><creatorcontrib>Beltrame, Luca</creatorcontrib><creatorcontrib>Porcu, Luca</creatorcontrib><creatorcontrib>Nerini, Ilaria Fuso</creatorcontrib><creatorcontrib>Cavalieri, Duccio</creatorcontrib><creatorcontrib>Chiorino, Giovanna</creatorcontrib><creatorcontrib>Cattoretti, Giorgio</creatorcontrib><creatorcontrib>Mangioni, Costantino</creatorcontrib><creatorcontrib>Milani, Rodolfo</creatorcontrib><creatorcontrib>Torri, Valter</creatorcontrib><creatorcontrib>Romualdi, Chiara</creatorcontrib><creatorcontrib>Zambelli, Alberto</creatorcontrib><creatorcontrib>Romano, Michela</creatorcontrib><creatorcontrib>Signorelli, Mauro</creatorcontrib><creatorcontrib>Giandomenico, Silvana di</creatorcontrib><creatorcontrib>D’Incalci, Maurizio</creatorcontrib><title>Resistance to platinum-based chemotherapy is associated with epithelial to mesenchymal transition in epithelial ovarian cancer</title><title>European journal of cancer (1990)</title><addtitle>Eur J Cancer</addtitle><description>Abstract Background The present study is aimed to identify genetic pathways correlated with chemoresistance in epithelial ovarian cancer (EOC). Methods We compared the molecular profiles of 23 tumour biopsies of stage III–IV (training set) at primary surgery, before chemotherapy, to the profile from the same patients at second surgery, after several lines of platinum (Pt)-based chemotherapy when the tumours were resistant. In the hypothesis that identified markers were related to Pt-resistance and to prognosis, we validated this signature in 52 EOC taken at primary surgery (validation set) selected to be either very sensitive to the first line therapy, i.e. not relapsing before one year from the end of therapy, or resistant, i.e. relapsing within 6 months from the end of therapy. Results In the training set, we identified a resistance signature indicative of the activation of epithelial to mesenchymal transition (EMT) by transforming growth factor (TGF)-beta pathway. We then validated this signature in 52 EOC taken at primary surgery (validation set). Some genes involved in EMT, such as B MP and a ctivin m embrane- b ound i nhibitor (BAMBI), and mir-141 resulted in association with overall or progression free survival. Conclusion Some genes involved in EMT were associated to overall or progression free survival, suggesting EMT as vital to the resistance mechanisms.</description><subject>Adult</subject><subject>Aged</subject><subject>Antineoplastic Combined Chemotherapy Protocols - therapeutic use</subject><subject>Biological and medical sciences</subject><subject>Biopsy</subject><subject>Carcinoma, Ovarian Epithelial</subject><subject>Disease-Free Survival</subject><subject>Drug Resistance, Neoplasm</subject><subject>Epithelial ovarian cancer</subject><subject>Epithelial to mesenchymal transition</subject><subject>Epithelial-Mesenchymal Transition - genetics</subject><subject>Female</subject><subject>Hematology, Oncology and Palliative Medicine</subject><subject>Humans</subject><subject>Medical sciences</subject><subject>Middle Aged</subject><subject>Neoplasm Staging</subject><subject>Neoplasms, Glandular and Epithelial - drug therapy</subject><subject>Neoplasms, Glandular and Epithelial - genetics</subject><subject>Neoplasms, Glandular and Epithelial - pathology</subject><subject>Organoplatinum Compounds - administration & dosage</subject><subject>Ovarian Neoplasms - drug therapy</subject><subject>Ovarian Neoplasms - genetics</subject><subject>Ovarian Neoplasms - pathology</subject><subject>Pharmacology. Drug treatments</subject><subject>Platinum-resistance</subject><subject>Signal Transduction</subject><subject>Treatment Outcome</subject><subject>Tumors</subject><issn>0959-8049</issn><issn>1879-0852</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2013</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9ksuL1TAUh4soznX0H3Ah3QhuWk_SpDcFEYbBFwwIPsBdOE1Pual9mdOO3I1_uyn3-sCFmzzI9zsn-UiSPBaQCxDl8y6nzmEuQcgcyhxkeSfZCbOvMjBa3k12UOkqM6Cqi-QBcwcAe6PgfnIhpam25S758YHY84Kjo3SZ0rnHxY_rkNXI1KTuQMO0HCjgfEw9p8g8OY9LPPrul0NKcxyp99hv4YGYRnc4Dts24Mh-8dOY-vFvbrrF4HFM3dYyPEzutdgzPTrPl8nn168-Xb_Nbt6_eXd9dZM5pcSS6aYqsa5Byj2hU6XUhdG6cFCbsqqIVNEYbKGESrZGCtVoBBlfWLQGoHFYXCbPTnXnMH1biRc7eHbU9zjStLIVcl8UWopCRVSeUBcm5kCtnYMfMBytALt5t53dvNvNu4XSRu8x9ORcf60Han5HfomOwNMzgOywb6Me5_kPVxpVaSUj9-LEUbRx6ylYdj5apcYHcottJv__e7z8J-56P_rY8SsdibtpDWP0bIXlmLEftx-yfRAhAXQpvxQ_AQyCt_k</recordid><startdate>20130101</startdate><enddate>20130101</enddate><creator>Marchini, Sergio</creator><creator>Fruscio, Robert</creator><creator>Clivio, Luca</creator><creator>Beltrame, Luca</creator><creator>Porcu, Luca</creator><creator>Nerini, Ilaria Fuso</creator><creator>Cavalieri, Duccio</creator><creator>Chiorino, Giovanna</creator><creator>Cattoretti, Giorgio</creator><creator>Mangioni, Costantino</creator><creator>Milani, Rodolfo</creator><creator>Torri, Valter</creator><creator>Romualdi, Chiara</creator><creator>Zambelli, Alberto</creator><creator>Romano, Michela</creator><creator>Signorelli, Mauro</creator><creator>Giandomenico, Silvana di</creator><creator>D’Incalci, Maurizio</creator><general>Elsevier Ltd</general><general>Elsevier</general><scope>IQODW</scope><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></search><sort><creationdate>20130101</creationdate><title>Resistance to platinum-based chemotherapy is associated with epithelial to mesenchymal transition in epithelial ovarian cancer</title><author>Marchini, Sergio ; Fruscio, Robert ; Clivio, Luca ; Beltrame, Luca ; Porcu, Luca ; Nerini, Ilaria Fuso ; Cavalieri, Duccio ; Chiorino, Giovanna ; Cattoretti, Giorgio ; Mangioni, Costantino ; Milani, Rodolfo ; Torri, Valter ; Romualdi, Chiara ; Zambelli, Alberto ; Romano, Michela ; Signorelli, Mauro ; Giandomenico, Silvana di ; D’Incalci, Maurizio</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c441t-5d96abb0227eac462538553c0b8699ee43d8af06092f8214d5a029783f800dca3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2013</creationdate><topic>Adult</topic><topic>Aged</topic><topic>Antineoplastic Combined Chemotherapy Protocols - therapeutic use</topic><topic>Biological and medical sciences</topic><topic>Biopsy</topic><topic>Carcinoma, Ovarian Epithelial</topic><topic>Disease-Free Survival</topic><topic>Drug Resistance, Neoplasm</topic><topic>Epithelial ovarian cancer</topic><topic>Epithelial to mesenchymal transition</topic><topic>Epithelial-Mesenchymal Transition - genetics</topic><topic>Female</topic><topic>Hematology, Oncology and Palliative Medicine</topic><topic>Humans</topic><topic>Medical sciences</topic><topic>Middle Aged</topic><topic>Neoplasm Staging</topic><topic>Neoplasms, Glandular and Epithelial - drug therapy</topic><topic>Neoplasms, Glandular and Epithelial - genetics</topic><topic>Neoplasms, Glandular and Epithelial - pathology</topic><topic>Organoplatinum Compounds - administration & dosage</topic><topic>Ovarian Neoplasms - drug therapy</topic><topic>Ovarian Neoplasms - genetics</topic><topic>Ovarian Neoplasms - pathology</topic><topic>Pharmacology. Drug treatments</topic><topic>Platinum-resistance</topic><topic>Signal Transduction</topic><topic>Treatment Outcome</topic><topic>Tumors</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Marchini, Sergio</creatorcontrib><creatorcontrib>Fruscio, Robert</creatorcontrib><creatorcontrib>Clivio, Luca</creatorcontrib><creatorcontrib>Beltrame, Luca</creatorcontrib><creatorcontrib>Porcu, Luca</creatorcontrib><creatorcontrib>Nerini, Ilaria Fuso</creatorcontrib><creatorcontrib>Cavalieri, Duccio</creatorcontrib><creatorcontrib>Chiorino, Giovanna</creatorcontrib><creatorcontrib>Cattoretti, Giorgio</creatorcontrib><creatorcontrib>Mangioni, Costantino</creatorcontrib><creatorcontrib>Milani, Rodolfo</creatorcontrib><creatorcontrib>Torri, Valter</creatorcontrib><creatorcontrib>Romualdi, Chiara</creatorcontrib><creatorcontrib>Zambelli, Alberto</creatorcontrib><creatorcontrib>Romano, Michela</creatorcontrib><creatorcontrib>Signorelli, Mauro</creatorcontrib><creatorcontrib>Giandomenico, Silvana di</creatorcontrib><creatorcontrib>D’Incalci, Maurizio</creatorcontrib><collection>Pascal-Francis</collection><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><jtitle>European journal of cancer (1990)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Marchini, Sergio</au><au>Fruscio, Robert</au><au>Clivio, Luca</au><au>Beltrame, Luca</au><au>Porcu, Luca</au><au>Nerini, Ilaria Fuso</au><au>Cavalieri, Duccio</au><au>Chiorino, Giovanna</au><au>Cattoretti, Giorgio</au><au>Mangioni, Costantino</au><au>Milani, Rodolfo</au><au>Torri, Valter</au><au>Romualdi, Chiara</au><au>Zambelli, Alberto</au><au>Romano, Michela</au><au>Signorelli, Mauro</au><au>Giandomenico, Silvana di</au><au>D’Incalci, Maurizio</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Resistance to platinum-based chemotherapy is associated with epithelial to mesenchymal transition in epithelial ovarian cancer</atitle><jtitle>European journal of cancer (1990)</jtitle><addtitle>Eur J Cancer</addtitle><date>2013-01-01</date><risdate>2013</risdate><volume>49</volume><issue>2</issue><spage>520</spage><epage>530</epage><pages>520-530</pages><issn>0959-8049</issn><eissn>1879-0852</eissn><abstract>Abstract Background The present study is aimed to identify genetic pathways correlated with chemoresistance in epithelial ovarian cancer (EOC). Methods We compared the molecular profiles of 23 tumour biopsies of stage III–IV (training set) at primary surgery, before chemotherapy, to the profile from the same patients at second surgery, after several lines of platinum (Pt)-based chemotherapy when the tumours were resistant. In the hypothesis that identified markers were related to Pt-resistance and to prognosis, we validated this signature in 52 EOC taken at primary surgery (validation set) selected to be either very sensitive to the first line therapy, i.e. not relapsing before one year from the end of therapy, or resistant, i.e. relapsing within 6 months from the end of therapy. Results In the training set, we identified a resistance signature indicative of the activation of epithelial to mesenchymal transition (EMT) by transforming growth factor (TGF)-beta pathway. We then validated this signature in 52 EOC taken at primary surgery (validation set). Some genes involved in EMT, such as B MP and a ctivin m embrane- b ound i nhibitor (BAMBI), and mir-141 resulted in association with overall or progression free survival. Conclusion Some genes involved in EMT were associated to overall or progression free survival, suggesting EMT as vital to the resistance mechanisms.</abstract><cop>Kidlington</cop><pub>Elsevier Ltd</pub><pmid>22897840</pmid><doi>10.1016/j.ejca.2012.06.026</doi><tpages>11</tpages></addata></record> |
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| subjects | Adult Aged Antineoplastic Combined Chemotherapy Protocols - therapeutic use Biological and medical sciences Biopsy Carcinoma, Ovarian Epithelial Disease-Free Survival Drug Resistance, Neoplasm Epithelial ovarian cancer Epithelial to mesenchymal transition Epithelial-Mesenchymal Transition - genetics Female Hematology, Oncology and Palliative Medicine Humans Medical sciences Middle Aged Neoplasm Staging Neoplasms, Glandular and Epithelial - drug therapy Neoplasms, Glandular and Epithelial - genetics Neoplasms, Glandular and Epithelial - pathology Organoplatinum Compounds - administration & dosage Ovarian Neoplasms - drug therapy Ovarian Neoplasms - genetics Ovarian Neoplasms - pathology Pharmacology. Drug treatments Platinum-resistance Signal Transduction Treatment Outcome Tumors |
| title | Resistance to platinum-based chemotherapy is associated with epithelial to mesenchymal transition in epithelial ovarian cancer |
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