Stathmin 1 is highly expressed and associated with survival outcome in malignant adrenocortical tumours
Adrenocortical carcinoma (ACC) is an aggressive endocrine cancer with few molecular predictors of malignancy and survival, especially in paediatric patients. Stathmin 1 (STMN1) regulates microtubule dynamics and has been involved in the malignant phenotype of cancer cells. Recently, it was reported...
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| Veröffentlicht in: | Investigational new drugs 2020-06, Vol.38 (3), p.899-908 |
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| creator | dos Santos Passaia, Bárbara Lima, Keli Kremer, Jean Lucas da Conceição, Barbara Brito de Paula Mariani, Beatriz Marinho da Silva, Jean Carlos Lipreri Zerbini, Maria Claudia Nogueira Fragoso, Maria Candida Barisson Villares Machado-Neto, João Agostinho Lotfi, Claudimara Ferini Pacicco |
| description | Adrenocortical carcinoma (ACC) is an aggressive endocrine cancer with few molecular predictors of malignancy and survival, especially in paediatric patients. Stathmin 1 (STMN1) regulates microtubule dynamics and has been involved in the malignant phenotype of cancer cells. Recently, it was reported that STMN1 is highly expressed in ACC patients, and STMN1 silencing reduces the clonogenicity and migration of ACC cell lines. However, the prognostic significance of STMN1 and its therapeutic potential remain undefined in ACC. In the present study,
STMN1
mRNA levels were significantly higher (
p
|
| doi_str_mv | 10.1007/s10637-019-00846-9 |
| format | Article |
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STMN1
mRNA levels were significantly higher (
p
< 0.05) in ACC patients, especially in an advanced stage, and correlated with
BUB1B
and
PINK1
expression, the prognostic-related genes in ACC. In paediatric tumours, high
STMN1
expression was observed in both adrenocortical carcinoma and adrenocortical adenoma patients. Among the adult malignant tumours,
STMN1
level was an independent predictor of survival outcomes (overall survival: hazard ratio = 6.08,
p
= 0.002; disease-free survival: hazard ratio = 4.65,
p
< 0.0001). Paclitaxel, a microtubule-stabilizing drug, reduces the activation of STMN1 and significantly decreases cell migration and invasion in ACC cell lines and ACC cells from secondary cell culture (all
p
< 0.0001). In summary, STMN1 expression may be of great value to clinical and pathological findings in therapeutic trials and deserves future studies in ACC.</description><identifier>ISSN: 0167-6997</identifier><identifier>EISSN: 1573-0646</identifier><identifier>DOI: 10.1007/s10637-019-00846-9</identifier><identifier>PMID: 31441020</identifier><language>eng</language><publisher>New York: Springer US</publisher><subject>Adenoma ; Biotechnology ; Cancer ; Cell adhesion & migration ; Cell culture ; Cell migration ; Clinical trials ; Gene expression ; Malignancy ; Medicine ; Medicine & Public Health ; mRNA ; Neuroendocrine tumors ; Oncology ; Paclitaxel ; Pediatrics ; Pharmacology/Toxicology ; Phenotypes ; PTEN-induced putative kinase ; Short Report ; Stathmin ; Survival ; Tumors</subject><ispartof>Investigational new drugs, 2020-06, Vol.38 (3), p.899-908</ispartof><rights>Springer Science+Business Media, LLC, part of Springer Nature 2019</rights><rights>Springer Science+Business Media, LLC, part of Springer Nature 2019.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c375t-802d5247e6869003bae8f3ef42a734fa1f0cd68b108e2180f499c27ed2e0b7e03</citedby><cites>FETCH-LOGICAL-c375t-802d5247e6869003bae8f3ef42a734fa1f0cd68b108e2180f499c27ed2e0b7e03</cites><orcidid>0000-0002-9881-7099</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1007/s10637-019-00846-9$$EPDF$$P50$$Gspringer$$H</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1007/s10637-019-00846-9$$EHTML$$P50$$Gspringer$$H</linktohtml><link.rule.ids>314,780,784,27923,27924,41487,42556,51318</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/31441020$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>dos Santos Passaia, Bárbara</creatorcontrib><creatorcontrib>Lima, Keli</creatorcontrib><creatorcontrib>Kremer, Jean Lucas</creatorcontrib><creatorcontrib>da Conceição, Barbara Brito</creatorcontrib><creatorcontrib>de Paula Mariani, Beatriz Marinho</creatorcontrib><creatorcontrib>da Silva, Jean Carlos Lipreri</creatorcontrib><creatorcontrib>Zerbini, Maria Claudia Nogueira</creatorcontrib><creatorcontrib>Fragoso, Maria Candida Barisson Villares</creatorcontrib><creatorcontrib>Machado-Neto, João Agostinho</creatorcontrib><creatorcontrib>Lotfi, Claudimara Ferini Pacicco</creatorcontrib><title>Stathmin 1 is highly expressed and associated with survival outcome in malignant adrenocortical tumours</title><title>Investigational new drugs</title><addtitle>Invest New Drugs</addtitle><addtitle>Invest New Drugs</addtitle><description>Adrenocortical carcinoma (ACC) is an aggressive endocrine cancer with few molecular predictors of malignancy and survival, especially in paediatric patients. Stathmin 1 (STMN1) regulates microtubule dynamics and has been involved in the malignant phenotype of cancer cells. Recently, it was reported that STMN1 is highly expressed in ACC patients, and STMN1 silencing reduces the clonogenicity and migration of ACC cell lines. However, the prognostic significance of STMN1 and its therapeutic potential remain undefined in ACC. In the present study,
STMN1
mRNA levels were significantly higher (
p
< 0.05) in ACC patients, especially in an advanced stage, and correlated with
BUB1B
and
PINK1
expression, the prognostic-related genes in ACC. In paediatric tumours, high
STMN1
expression was observed in both adrenocortical carcinoma and adrenocortical adenoma patients. Among the adult malignant tumours,
STMN1
level was an independent predictor of survival outcomes (overall survival: hazard ratio = 6.08,
p
= 0.002; disease-free survival: hazard ratio = 4.65,
p
< 0.0001). Paclitaxel, a microtubule-stabilizing drug, reduces the activation of STMN1 and significantly decreases cell migration and invasion in ACC cell lines and ACC cells from secondary cell culture (all
p
< 0.0001). In summary, STMN1 expression may be of great value to clinical and pathological findings in therapeutic trials and deserves future studies in ACC.</description><subject>Adenoma</subject><subject>Biotechnology</subject><subject>Cancer</subject><subject>Cell adhesion & migration</subject><subject>Cell culture</subject><subject>Cell migration</subject><subject>Clinical trials</subject><subject>Gene expression</subject><subject>Malignancy</subject><subject>Medicine</subject><subject>Medicine & Public Health</subject><subject>mRNA</subject><subject>Neuroendocrine tumors</subject><subject>Oncology</subject><subject>Paclitaxel</subject><subject>Pediatrics</subject><subject>Pharmacology/Toxicology</subject><subject>Phenotypes</subject><subject>PTEN-induced putative kinase</subject><subject>Short 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Bárbara</creator><creator>Lima, Keli</creator><creator>Kremer, Jean Lucas</creator><creator>da Conceição, Barbara Brito</creator><creator>de Paula Mariani, Beatriz Marinho</creator><creator>da Silva, Jean Carlos Lipreri</creator><creator>Zerbini, Maria Claudia Nogueira</creator><creator>Fragoso, Maria Candida Barisson Villares</creator><creator>Machado-Neto, João Agostinho</creator><creator>Lotfi, Claudimara Ferini Pacicco</creator><general>Springer US</general><general>Springer Nature 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1 is highly expressed and associated with survival outcome in malignant adrenocortical tumours</title><author>dos Santos Passaia, Bárbara ; Lima, Keli ; Kremer, Jean Lucas ; da Conceição, Barbara Brito ; de Paula Mariani, Beatriz Marinho ; da Silva, Jean Carlos Lipreri ; Zerbini, Maria Claudia Nogueira ; Fragoso, Maria Candida Barisson Villares ; Machado-Neto, João Agostinho ; Lotfi, Claudimara Ferini Pacicco</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c375t-802d5247e6869003bae8f3ef42a734fa1f0cd68b108e2180f499c27ed2e0b7e03</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2020</creationdate><topic>Adenoma</topic><topic>Biotechnology</topic><topic>Cancer</topic><topic>Cell adhesion & migration</topic><topic>Cell culture</topic><topic>Cell migration</topic><topic>Clinical trials</topic><topic>Gene expression</topic><topic>Malignancy</topic><topic>Medicine</topic><topic>Medicine & Public Health</topic><topic>mRNA</topic><topic>Neuroendocrine tumors</topic><topic>Oncology</topic><topic>Paclitaxel</topic><topic>Pediatrics</topic><topic>Pharmacology/Toxicology</topic><topic>Phenotypes</topic><topic>PTEN-induced putative kinase</topic><topic>Short Report</topic><topic>Stathmin</topic><topic>Survival</topic><topic>Tumors</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>dos Santos Passaia, Bárbara</creatorcontrib><creatorcontrib>Lima, Keli</creatorcontrib><creatorcontrib>Kremer, Jean Lucas</creatorcontrib><creatorcontrib>da Conceição, Barbara Brito</creatorcontrib><creatorcontrib>de Paula Mariani, Beatriz Marinho</creatorcontrib><creatorcontrib>da Silva, Jean Carlos Lipreri</creatorcontrib><creatorcontrib>Zerbini, Maria Claudia Nogueira</creatorcontrib><creatorcontrib>Fragoso, Maria Candida Barisson Villares</creatorcontrib><creatorcontrib>Machado-Neto, João Agostinho</creatorcontrib><creatorcontrib>Lotfi, Claudimara Ferini 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Paula Mariani, Beatriz Marinho</au><au>da Silva, Jean Carlos Lipreri</au><au>Zerbini, Maria Claudia Nogueira</au><au>Fragoso, Maria Candida Barisson Villares</au><au>Machado-Neto, João Agostinho</au><au>Lotfi, Claudimara Ferini Pacicco</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Stathmin 1 is highly expressed and associated with survival outcome in malignant adrenocortical tumours</atitle><jtitle>Investigational new drugs</jtitle><stitle>Invest New Drugs</stitle><addtitle>Invest New Drugs</addtitle><date>2020-06-01</date><risdate>2020</risdate><volume>38</volume><issue>3</issue><spage>899</spage><epage>908</epage><pages>899-908</pages><issn>0167-6997</issn><eissn>1573-0646</eissn><abstract>Adrenocortical carcinoma (ACC) is an aggressive endocrine cancer with few molecular predictors of malignancy and survival, especially in paediatric patients. Stathmin 1 (STMN1) regulates microtubule dynamics and has been involved in the malignant phenotype of cancer cells. Recently, it was reported that STMN1 is highly expressed in ACC patients, and STMN1 silencing reduces the clonogenicity and migration of ACC cell lines. However, the prognostic significance of STMN1 and its therapeutic potential remain undefined in ACC. In the present study,
STMN1
mRNA levels were significantly higher (
p
< 0.05) in ACC patients, especially in an advanced stage, and correlated with
BUB1B
and
PINK1
expression, the prognostic-related genes in ACC. In paediatric tumours, high
STMN1
expression was observed in both adrenocortical carcinoma and adrenocortical adenoma patients. Among the adult malignant tumours,
STMN1
level was an independent predictor of survival outcomes (overall survival: hazard ratio = 6.08,
p
= 0.002; disease-free survival: hazard ratio = 4.65,
p
< 0.0001). Paclitaxel, a microtubule-stabilizing drug, reduces the activation of STMN1 and significantly decreases cell migration and invasion in ACC cell lines and ACC cells from secondary cell culture (all
p
< 0.0001). In summary, STMN1 expression may be of great value to clinical and pathological findings in therapeutic trials and deserves future studies in ACC.</abstract><cop>New York</cop><pub>Springer US</pub><pmid>31441020</pmid><doi>10.1007/s10637-019-00846-9</doi><tpages>10</tpages><orcidid>https://orcid.org/0000-0002-9881-7099</orcidid></addata></record> |
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| language | eng |
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| subjects | Adenoma Biotechnology Cancer Cell adhesion & migration Cell culture Cell migration Clinical trials Gene expression Malignancy Medicine Medicine & Public Health mRNA Neuroendocrine tumors Oncology Paclitaxel Pediatrics Pharmacology/Toxicology Phenotypes PTEN-induced putative kinase Short Report Stathmin Survival Tumors |
| title | Stathmin 1 is highly expressed and associated with survival outcome in malignant adrenocortical tumours |
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