Gene expression of somatostatin receptor 4 predicts clinical outcome of patients with metastatic neuroendocrine tumors treated with somatostatin analogs.
Identifieur interne : 001970 ( Main/Exploration ); précédent : 001969; suivant : 001971Gene expression of somatostatin receptor 4 predicts clinical outcome of patients with metastatic neuroendocrine tumors treated with somatostatin analogs.
Auteurs : RBID : pubmed:20423238English descriptors
- KwdEn :
- Adult, Aged, Aged, 80 and over, Antineoplastic Agents, Hormonal (therapeutic use), Female, Follow-Up Studies, Gene Expression (drug effects), Humans, Indium Radioisotopes (diagnostic use), Liver Neoplasms (drug therapy), Liver Neoplasms (genetics), Liver Neoplasms (secondary), Lymphatic Metastasis, Male, Mediastinal Neoplasms (drug therapy), Mediastinal Neoplasms (genetics), Mediastinal Neoplasms (secondary), Middle Aged, Neuroendocrine Tumors (drug therapy), Neuroendocrine Tumors (genetics), Neuroendocrine Tumors (pathology), Octreotide (therapeutic use), Peritoneal Neoplasms (drug therapy), Peritoneal Neoplasms (genetics), Peritoneal Neoplasms (secondary), RNA, Messenger (genetics), Receptors, Somatostatin (genetics), Reverse Transcriptase Polymerase Chain Reaction, Survival Rate, Treatment Outcome.
- MESH :
- chemical , diagnostic use : Indium Radioisotopes.
- chemical , genetics : RNA, Messenger, Receptors, Somatostatin.
- chemical , therapeutic use : Antineoplastic Agents, Hormonal, Octreotide.
- drug effects : Gene Expression.
- drug therapy : Liver Neoplasms, Mediastinal Neoplasms, Neuroendocrine Tumors, Peritoneal Neoplasms.
- genetics : Liver Neoplasms, Mediastinal Neoplasms, Neuroendocrine Tumors, Peritoneal Neoplasms.
- pathology : Neuroendocrine Tumors.
- secondary : Liver Neoplasms, Mediastinal Neoplasms, Peritoneal Neoplasms.
- Adult, Aged, Aged, 80 and over, Female, Follow-Up Studies, Humans, Lymphatic Metastasis, Male, Middle Aged, Reverse Transcriptase Polymerase Chain Reaction, Survival Rate, Treatment Outcome.
Abstract
Somatostatin analogs (SSA) are the standard diagnostic and treatment tools in the clinical management of patients with neuroendocrine tumors (NETs) expressing somatostatin receptors (SSTRs). Although symptomatic and biochemical control is obtained with SSA in the majority of functional NETs, antineoplastic effects of SSA are partial and of limited duration. The aim of this study was to quantify expression levels of five SSTR subtypes (SSTR1-SSTR5) and correlate them with the clinical outcomes of patients with NETs who underwent SSA therapy. The expression levels were analyzed using real-time polymerase chain reaction in a series of 22 metastatic NETs with a median time of 10 months on the SSA therapy (range 2-82 months). The median duration of disease stabilization in patients who developed progression (n = 14) was 9 months (range 3-92 months). The median survival period for all patients was 44 months (range 3-175 months). According to RECIST criteria, one (5%) partial objective tumor response was obtained, disease stabilization was achieved in 10 (45%) patients, and progressive disease was observed in 11 (50%). Analysis of mRNA expression of the SSTR subtypes showed that SSTR2 and SSTR5 were expressed in all of the studied NETs; SSTR1 and SSTR4 in all but 3 tumors (86%); and SSTR3 in only 10 NETs (49%). Interestingly, our preliminary data suggest that only the levels of SSTR4, though it has the lowest affinity for SSA of all SSTR subtypes, were significantly associated with the stabilization of disease during SSA therapy (p = 0.0357). These levels correlated with time to progression (p = 0.0015) and overall survival (p = 0.0017) in NET patients.
DOI: 10.1089/cbr.2009.0708
PubMed: 20423238
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<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Gene expression of somatostatin receptor 4 predicts clinical outcome of patients with metastatic neuroendocrine tumors treated with somatostatin analogs.</title><author><name sortKey="Slaby, Ondrej" uniqKey="Slaby O">Ondrej Slaby</name><affiliation wicri:level="1"><nlm:affiliation>Department of Comprehensive Cancer Care, Masaryk Memorial Cancer Institute, Brno, Czech Republic. slaby@mou.cz</nlm:affiliation><country xml:lang="fr">République tchèque</country><wicri:regionArea>Department of Comprehensive Cancer Care, Masaryk Memorial Cancer Institute, Brno</wicri:regionArea></affiliation></author><author><name sortKey="Sachlova, Milana" uniqKey="Sachlova M">Milana Sachlova</name></author><author><name sortKey="Bednarikova, Marketa" uniqKey="Bednarikova M">Marketa Bednarikova</name></author><author><name sortKey="Fabian, Pavel" uniqKey="Fabian P">Pavel Fabian</name></author><author><name sortKey="Svoboda, Marek" uniqKey="Svoboda M">Marek Svoboda</name></author><author><name sortKey="Vytopilova, Simona" uniqKey="Vytopilova S">Simona Vytopilova</name></author><author><name sortKey="Valik, Dalibor" uniqKey="Valik D">Dalibor Valik</name></author><author><name sortKey="Vyzula, Rostislav" uniqKey="Vyzula R">Rostislav Vyzula</name></author></titleStmt><publicationStmt><date when="2010">2010</date><idno type="doi">10.1089/cbr.2009.0708</idno><idno type="RBID">pubmed:20423238</idno><idno type="pmid">20423238</idno><idno type="wicri:Area/Main/Corpus">001953</idno><idno type="wicri:Area/Main/Curation">001953</idno><idno type="wicri:Area/Main/Exploration">001970</idno></publicationStmt></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Adult</term><term>Aged</term><term>Aged, 80 and over</term><term>Antineoplastic Agents, Hormonal (therapeutic use)</term><term>Female</term><term>Follow-Up Studies</term><term>Gene Expression (drug effects)</term><term>Humans</term><term>Indium Radioisotopes (diagnostic use)</term><term>Liver Neoplasms (drug therapy)</term><term>Liver Neoplasms (genetics)</term><term>Liver Neoplasms (secondary)</term><term>Lymphatic Metastasis</term><term>Male</term><term>Mediastinal Neoplasms (drug therapy)</term><term>Mediastinal Neoplasms (genetics)</term><term>Mediastinal Neoplasms (secondary)</term><term>Middle Aged</term><term>Neuroendocrine Tumors (drug therapy)</term><term>Neuroendocrine Tumors (genetics)</term><term>Neuroendocrine Tumors (pathology)</term><term>Octreotide (therapeutic use)</term><term>Peritoneal Neoplasms (drug therapy)</term><term>Peritoneal Neoplasms (genetics)</term><term>Peritoneal Neoplasms (secondary)</term><term>RNA, Messenger (genetics)</term><term>Receptors, Somatostatin (genetics)</term><term>Reverse Transcriptase Polymerase Chain Reaction</term><term>Survival Rate</term><term>Treatment Outcome</term></keywords><keywords scheme="MESH" type="chemical" qualifier="diagnostic use" xml:lang="en"><term>Indium Radioisotopes</term></keywords><keywords scheme="MESH" type="chemical" qualifier="genetics" xml:lang="en"><term>RNA, Messenger</term><term>Receptors, Somatostatin</term></keywords><keywords scheme="MESH" type="chemical" qualifier="therapeutic use" xml:lang="en"><term>Antineoplastic Agents, Hormonal</term><term>Octreotide</term></keywords><keywords scheme="MESH" qualifier="drug effects" xml:lang="en"><term>Gene Expression</term></keywords><keywords scheme="MESH" qualifier="drug therapy" xml:lang="en"><term>Liver Neoplasms</term><term>Mediastinal Neoplasms</term><term>Neuroendocrine Tumors</term><term>Peritoneal Neoplasms</term></keywords><keywords scheme="MESH" qualifier="genetics" xml:lang="en"><term>Liver Neoplasms</term><term>Mediastinal Neoplasms</term><term>Neuroendocrine Tumors</term><term>Peritoneal Neoplasms</term></keywords><keywords scheme="MESH" qualifier="pathology" xml:lang="en"><term>Neuroendocrine Tumors</term></keywords><keywords scheme="MESH" qualifier="secondary" xml:lang="en"><term>Liver Neoplasms</term><term>Mediastinal Neoplasms</term><term>Peritoneal Neoplasms</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Adult</term><term>Aged</term><term>Aged, 80 and over</term><term>Female</term><term>Follow-Up Studies</term><term>Humans</term><term>Lymphatic Metastasis</term><term>Male</term><term>Middle Aged</term><term>Reverse Transcriptase Polymerase Chain Reaction</term><term>Survival Rate</term><term>Treatment Outcome</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Somatostatin analogs (SSA) are the standard diagnostic and treatment tools in the clinical management of patients with neuroendocrine tumors (NETs) expressing somatostatin receptors (SSTRs). Although symptomatic and biochemical control is obtained with SSA in the majority of functional NETs, antineoplastic effects of SSA are partial and of limited duration. The aim of this study was to quantify expression levels of five SSTR subtypes (SSTR1-SSTR5) and correlate them with the clinical outcomes of patients with NETs who underwent SSA therapy. The expression levels were analyzed using real-time polymerase chain reaction in a series of 22 metastatic NETs with a median time of 10 months on the SSA therapy (range 2-82 months). The median duration of disease stabilization in patients who developed progression (n = 14) was 9 months (range 3-92 months). The median survival period for all patients was 44 months (range 3-175 months). According to RECIST criteria, one (5%) partial objective tumor response was obtained, disease stabilization was achieved in 10 (45%) patients, and progressive disease was observed in 11 (50%). Analysis of mRNA expression of the SSTR subtypes showed that SSTR2 and SSTR5 were expressed in all of the studied NETs; SSTR1 and SSTR4 in all but 3 tumors (86%); and SSTR3 in only 10 NETs (49%). Interestingly, our preliminary data suggest that only the levels of SSTR4, though it has the lowest affinity for SSA of all SSTR subtypes, were significantly associated with the stabilization of disease during SSA therapy (p = 0.0357). These levels correlated with time to progression (p = 0.0015) and overall survival (p = 0.0017) in NET patients.</div></front></TEI><pubmed><MedlineCitation Owner="NLM" Status="MEDLINE"><PMID Version="1">20423238</PMID><DateCreated><Year>2010</Year><Month>04</Month><Day>28</Day></DateCreated><DateCompleted><Year>2010</Year><Month>08</Month><Day>10</Day></DateCompleted><DateRevised><Year>2013</Year><Month>11</Month><Day>21</Day></DateRevised><Article PubModel="Print"><Journal><ISSN IssnType="Electronic">1557-8852</ISSN><JournalIssue CitedMedium="Internet"><Volume>25</Volume><Issue>2</Issue><PubDate><Year>2010</Year><Month>Apr</Month></PubDate></JournalIssue><Title>Cancer biotherapy & radiopharmaceuticals</Title><ISOAbbreviation>Cancer Biother. Radiopharm.</ISOAbbreviation></Journal><ArticleTitle>Gene expression of somatostatin receptor 4 predicts clinical outcome of patients with metastatic neuroendocrine tumors treated with somatostatin analogs.</ArticleTitle><Pagination><MedlinePgn>237-43</MedlinePgn></Pagination><ELocationID EIdType="doi" ValidYN="Y">10.1089/cbr.2009.0708</ELocationID><Abstract><AbstractText>Somatostatin analogs (SSA) are the standard diagnostic and treatment tools in the clinical management of patients with neuroendocrine tumors (NETs) expressing somatostatin receptors (SSTRs). Although symptomatic and biochemical control is obtained with SSA in the majority of functional NETs, antineoplastic effects of SSA are partial and of limited duration. The aim of this study was to quantify expression levels of five SSTR subtypes (SSTR1-SSTR5) and correlate them with the clinical outcomes of patients with NETs who underwent SSA therapy. The expression levels were analyzed using real-time polymerase chain reaction in a series of 22 metastatic NETs with a median time of 10 months on the SSA therapy (range 2-82 months). The median duration of disease stabilization in patients who developed progression (n = 14) was 9 months (range 3-92 months). The median survival period for all patients was 44 months (range 3-175 months). According to RECIST criteria, one (5%) partial objective tumor response was obtained, disease stabilization was achieved in 10 (45%) patients, and progressive disease was observed in 11 (50%). Analysis of mRNA expression of the SSTR subtypes showed that SSTR2 and SSTR5 were expressed in all of the studied NETs; SSTR1 and SSTR4 in all but 3 tumors (86%); and SSTR3 in only 10 NETs (49%). Interestingly, our preliminary data suggest that only the levels of SSTR4, though it has the lowest affinity for SSA of all SSTR subtypes, were significantly associated with the stabilization of disease during SSA therapy (p = 0.0357). These levels correlated with time to progression (p = 0.0015) and overall survival (p = 0.0017) in NET patients.</AbstractText></Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Slaby</LastName><ForeName>Ondrej</ForeName><Initials>O</Initials><Affiliation>Department of Comprehensive Cancer Care, Masaryk Memorial Cancer Institute, Brno, Czech Republic. slaby@mou.cz</Affiliation></Author><Author ValidYN="Y"><LastName>Sachlova</LastName><ForeName>Milana</ForeName><Initials>M</Initials></Author><Author ValidYN="Y"><LastName>Bednarikova</LastName><ForeName>Marketa</ForeName><Initials>M</Initials></Author><Author ValidYN="Y"><LastName>Fabian</LastName><ForeName>Pavel</ForeName><Initials>P</Initials></Author><Author ValidYN="Y"><LastName>Svoboda</LastName><ForeName>Marek</ForeName><Initials>M</Initials></Author><Author ValidYN="Y"><LastName>Vytopilova</LastName><ForeName>Simona</ForeName><Initials>S</Initials></Author><Author ValidYN="Y"><LastName>Valik</LastName><ForeName>Dalibor</ForeName><Initials>D</Initials></Author><Author ValidYN="Y"><LastName>Vyzula</LastName><ForeName>Rostislav</ForeName><Initials>R</Initials></Author></AuthorList><Language>eng</Language><PublicationTypeList><PublicationType>Journal Article</PublicationType><PublicationType>Research Support, Non-U.S. Gov't</PublicationType></PublicationTypeList></Article><MedlineJournalInfo><Country>United States</Country><MedlineTA>Cancer Biother Radiopharm</MedlineTA><NlmUniqueID>9605408</NlmUniqueID><ISSNLinking>1084-9785</ISSNLinking></MedlineJournalInfo><ChemicalList><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance>Antineoplastic Agents, Hormonal</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance>Indium Radioisotopes</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance>RNA, Messenger</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance>Receptors, Somatostatin</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance>somatostatin receptor subtype-4</NameOfSubstance></Chemical><Chemical><RegistryNumber>RWM8CCW8GP</RegistryNumber><NameOfSubstance>Octreotide</NameOfSubstance></Chemical></ChemicalList><CitationSubset>IM</CitationSubset><MeshHeadingList><MeshHeading><DescriptorName MajorTopicYN="N">Adult</DescriptorName></MeshHeading><MeshHeading><DescriptorName MajorTopicYN="N">Aged</DescriptorName></MeshHeading><MeshHeading><DescriptorName MajorTopicYN="N">Aged, 80 and over</DescriptorName></MeshHeading><MeshHeading><DescriptorName MajorTopicYN="N">Antineoplastic Agents, Hormonal</DescriptorName><QualifierName MajorTopicYN="Y">therapeutic use</QualifierName></MeshHeading><MeshHeading><DescriptorName MajorTopicYN="N">Female</DescriptorName></MeshHeading><MeshHeading><DescriptorName 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MajorTopicYN="N">drug therapy</QualifierName><QualifierName MajorTopicYN="N">genetics</QualifierName><QualifierName MajorTopicYN="N">secondary</QualifierName></MeshHeading><MeshHeading><DescriptorName MajorTopicYN="N">Middle Aged</DescriptorName></MeshHeading><MeshHeading><DescriptorName MajorTopicYN="N">Neuroendocrine Tumors</DescriptorName><QualifierName MajorTopicYN="Y">drug therapy</QualifierName><QualifierName MajorTopicYN="Y">genetics</QualifierName><QualifierName MajorTopicYN="N">pathology</QualifierName></MeshHeading><MeshHeading><DescriptorName MajorTopicYN="N">Octreotide</DescriptorName><QualifierName MajorTopicYN="Y">therapeutic use</QualifierName></MeshHeading><MeshHeading><DescriptorName MajorTopicYN="N">Peritoneal Neoplasms</DescriptorName><QualifierName MajorTopicYN="N">drug therapy</QualifierName><QualifierName MajorTopicYN="N">genetics</QualifierName><QualifierName MajorTopicYN="N">secondary</QualifierName></MeshHeading><MeshHeading><DescriptorName MajorTopicYN="N">RNA, Messenger</DescriptorName><QualifierName MajorTopicYN="N">genetics</QualifierName></MeshHeading><MeshHeading><DescriptorName MajorTopicYN="N">Receptors, Somatostatin</DescriptorName><QualifierName MajorTopicYN="Y">genetics</QualifierName></MeshHeading><MeshHeading><DescriptorName MajorTopicYN="N">Reverse Transcriptase Polymerase Chain Reaction</DescriptorName></MeshHeading><MeshHeading><DescriptorName MajorTopicYN="N">Survival Rate</DescriptorName></MeshHeading><MeshHeading><DescriptorName MajorTopicYN="N">Treatment Outcome</DescriptorName></MeshHeading></MeshHeadingList></MedlineCitation><PubmedData><History><PubMedPubDate PubStatus="entrez"><Year>2010</Year><Month>4</Month><Day>29</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="pubmed"><Year>2010</Year><Month>4</Month><Day>29</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate 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