Low expression of the putative tumour suppressor spinophilin is associated with higher proliferative activity and poor prognosis in patients with hepatocellular carcinoma
Background: Spinophilin, a multifunctional intracellular scaffold protein, is reduced in certain types of cancer and is regarded as a novel putative tumour suppressor protein. However, the role of spinophilin in hepatocellular carcinoma (HCC) has never been explored before. Methods: In this study, w...
Gespeichert in:
| Veröffentlicht in: | British journal of cancer 2013-05, Vol.108 (9), p.1830-1837 |
|---|---|
| Hauptverfasser: | , , , , , , , , , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | 1837 |
|---|---|
| container_issue | 9 |
| container_start_page | 1830 |
| container_title | British journal of cancer |
| container_volume | 108 |
| creator | Aigelsreiter, A Ress, A L Bettermann, K Schauer, S Koller, K Eisner, F Kiesslich, T Stojakovic, T Samonigg, H Kornprat, P Lackner, C Haybaeck, J Pichler, M |
| description | Background:
Spinophilin, a multifunctional intracellular scaffold protein, is reduced in certain types of cancer and is regarded as a novel putative tumour suppressor protein. However, the role of spinophilin in hepatocellular carcinoma (HCC) has never been explored before.
Methods:
In this study, we determined for the first time the expression pattern of spinophilin in human HCC by immunohistochemistry and quantitative reverse transcriptase–PCR analysis. In addition, we performed immunohistochemical analysis of p53, p14
ARF
and the proliferation marker Ki-67. Kaplan–Meier curves and multivariate Cox proportional models were used to study the impact on clinical outcome. Small interfering RNA (siRNA) was used to silence spinophilin and to explore the effects of reduced spinophilin expression on cellular growth.
Results:
In our study, complete loss of spinophilin immunoreactivity was found in 44 of 104 HCCs (42.3%) and reduced levels were found in an additional 37 (35.6%) cases. After adjusting for other prognostic factors, multivariate Cox regression analysis identified low expression of spinophilin as an independent prognostic factor with respect to disease-free (hazard ratio (HR)=1.8; 95% confidence interval (CI)=1.04–3.40;
P
=0.043) and cancer-specific survival (HR=2.0; CI=1.1–3.8;
P
=0.025). Reduced spinophilin expression significantly correlated with higher Ki-67 index in HCC (
P
=0.014). Reducing spinophilin levels by siRNA induced a higher cellular growth rate and increased cyclin D2 expression in tumour cells (
P |
| doi_str_mv | 10.1038/bjc.2013.165 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_pubme</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_3658515</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>1367488045</sourcerecordid><originalsourceid>FETCH-LOGICAL-c513t-187edd91008fbe820517b8afc344df0d2cf518831623c092ebb0c7688039b9e3</originalsourceid><addsrcrecordid>eNqNkstu1DAUhi0EosPAjjWyhJBYkMGXOHY2SKjiJo3EpnvLcZyJRxk72ElLX6lP2ZPOUApiwco-Pp_-c_GP0EtKNpRw9b7Z2w0jlG9oJR6hFRWcFVQx-RitCCGyIDUjZ-hZznsIa6LkU3TGuKgprasVutnGK-x-jsnl7GPAscNT7_A4T2bylw5P8yHOCed5vEMiXEcf4tj7wQfsMzbwaL2ZXIuv_NTj3u96l_CY4uA7l44qxsLhp2tsQovHGO_yuxAzCIDMCJQLUz4pOIijdcMwDyZha5KFigfzHD3pzJDdi9O5RhefP12cfy223798O_-4LaygfILZpWvbmhKiusYpRgSVjTKd5WXZdqRlthNUKU4rxi0sxzUNsbJSivC6qR1fow9H2XFuDq610Fgygx6TP5h0raPx-s9M8L3exUvNK6EErH-N3p4EUvwxuzzpg8_LOCa4OGdNeSVLKFf-DyoYk0rUBNDXf6F7-JgAi1goUlNJqhKod0fKpphzct1935ToxS4a7KIXu2iwC-CvHs56D__yBwBvToDJ1gxdMsH6_JuTXMhaLXWLI5chFXYuPejuX4VvAV9w3JQ</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>1350917064</pqid></control><display><type>article</type><title>Low expression of the putative tumour suppressor spinophilin is associated with higher proliferative activity and poor prognosis in patients with hepatocellular carcinoma</title><source>MEDLINE</source><source>Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals</source><source>Nature Journals Online</source><source>PubMed Central</source><creator>Aigelsreiter, A ; Ress, A L ; Bettermann, K ; Schauer, S ; Koller, K ; Eisner, F ; Kiesslich, T ; Stojakovic, T ; Samonigg, H ; Kornprat, P ; Lackner, C ; Haybaeck, J ; Pichler, M</creator><creatorcontrib>Aigelsreiter, A ; Ress, A L ; Bettermann, K ; Schauer, S ; Koller, K ; Eisner, F ; Kiesslich, T ; Stojakovic, T ; Samonigg, H ; Kornprat, P ; Lackner, C ; Haybaeck, J ; Pichler, M</creatorcontrib><description>Background:
Spinophilin, a multifunctional intracellular scaffold protein, is reduced in certain types of cancer and is regarded as a novel putative tumour suppressor protein. However, the role of spinophilin in hepatocellular carcinoma (HCC) has never been explored before.
Methods:
In this study, we determined for the first time the expression pattern of spinophilin in human HCC by immunohistochemistry and quantitative reverse transcriptase–PCR analysis. In addition, we performed immunohistochemical analysis of p53, p14
ARF
and the proliferation marker Ki-67. Kaplan–Meier curves and multivariate Cox proportional models were used to study the impact on clinical outcome. Small interfering RNA (siRNA) was used to silence spinophilin and to explore the effects of reduced spinophilin expression on cellular growth.
Results:
In our study, complete loss of spinophilin immunoreactivity was found in 44 of 104 HCCs (42.3%) and reduced levels were found in an additional 37 (35.6%) cases. After adjusting for other prognostic factors, multivariate Cox regression analysis identified low expression of spinophilin as an independent prognostic factor with respect to disease-free (hazard ratio (HR)=1.8; 95% confidence interval (CI)=1.04–3.40;
P
=0.043) and cancer-specific survival (HR=2.0; CI=1.1–3.8;
P
=0.025). Reduced spinophilin expression significantly correlated with higher Ki-67 index in HCC (
P
=0.014). Reducing spinophilin levels by siRNA induced a higher cellular growth rate and increased cyclin D2 expression in tumour cells (
P
<0.05).
Conclusion:
This is the first study of the expression pattern and distribution of spinophilin in HCC. According to our data, the loss of spinophilin is associated with higher proliferation and might be useful as a prognostic marker in patients with HCC.</description><identifier>ISSN: 0007-0920</identifier><identifier>EISSN: 1532-1827</identifier><identifier>DOI: 10.1038/bjc.2013.165</identifier><identifier>PMID: 23591196</identifier><identifier>CODEN: BJCAAI</identifier><language>eng</language><publisher>London: Nature Publishing Group UK</publisher><subject>692/699/67/1504/1610 ; 692/699/67/1857 ; 692/699/67/581 ; 692/700/1750 ; Biological and medical sciences ; Biomarkers ; Biomarkers, Tumor - metabolism ; Biomedical and Life Sciences ; Biomedicine ; Cancer Research ; Carcinoma, Hepatocellular - metabolism ; Carcinoma, Hepatocellular - mortality ; Cell Line, Tumor ; Cell Proliferation ; Cyclin D2 - biosynthesis ; Disease-Free Survival ; Drug Resistance ; Epidemiology ; Female ; Gastroenterology. Liver. Pancreas. Abdomen ; Hep G2 Cells ; Humans ; Internal medicine ; Kaplan-Meier Estimate ; Ki-67 Antigen - metabolism ; Liver cancer ; Liver Neoplasms - metabolism ; Liver Neoplasms - mortality ; Liver. Biliary tract. Portal circulation. Exocrine pancreas ; Male ; Medical prognosis ; Medical sciences ; Microfilament Proteins - genetics ; Microfilament Proteins - metabolism ; Molecular Diagnostics ; Molecular Medicine ; Multiple tumors. Solid tumors. Tumors in childhood (general aspects) ; Nerve Tissue Proteins - genetics ; Nerve Tissue Proteins - metabolism ; Oncology ; Prognosis ; Proportional Hazards Models ; Proteins ; RNA Interference ; RNA, Small Interfering ; Surveillance ; Survival Rate ; Tumor Suppressor Protein p14ARF - metabolism ; Tumor Suppressor Protein p53 - metabolism ; Tumor Suppressor Proteins - genetics ; Tumor Suppressor Proteins - metabolism ; Tumors</subject><ispartof>British journal of cancer, 2013-05, Vol.108 (9), p.1830-1837</ispartof><rights>The Author(s) 2013</rights><rights>2014 INIST-CNRS</rights><rights>Copyright Nature Publishing Group May 14, 2013</rights><rights>Copyright © 2013 Cancer Research UK 2013 Cancer Research UK</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c513t-187edd91008fbe820517b8afc344df0d2cf518831623c092ebb0c7688039b9e3</citedby><cites>FETCH-LOGICAL-c513t-187edd91008fbe820517b8afc344df0d2cf518831623c092ebb0c7688039b9e3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3658515/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3658515/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,315,729,782,786,887,27931,27932,53798,53800</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=27357984$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/23591196$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Aigelsreiter, A</creatorcontrib><creatorcontrib>Ress, A L</creatorcontrib><creatorcontrib>Bettermann, K</creatorcontrib><creatorcontrib>Schauer, S</creatorcontrib><creatorcontrib>Koller, K</creatorcontrib><creatorcontrib>Eisner, F</creatorcontrib><creatorcontrib>Kiesslich, T</creatorcontrib><creatorcontrib>Stojakovic, T</creatorcontrib><creatorcontrib>Samonigg, H</creatorcontrib><creatorcontrib>Kornprat, P</creatorcontrib><creatorcontrib>Lackner, C</creatorcontrib><creatorcontrib>Haybaeck, J</creatorcontrib><creatorcontrib>Pichler, M</creatorcontrib><title>Low expression of the putative tumour suppressor spinophilin is associated with higher proliferative activity and poor prognosis in patients with hepatocellular carcinoma</title><title>British journal of cancer</title><addtitle>Br J Cancer</addtitle><addtitle>Br J Cancer</addtitle><description>Background:
Spinophilin, a multifunctional intracellular scaffold protein, is reduced in certain types of cancer and is regarded as a novel putative tumour suppressor protein. However, the role of spinophilin in hepatocellular carcinoma (HCC) has never been explored before.
Methods:
In this study, we determined for the first time the expression pattern of spinophilin in human HCC by immunohistochemistry and quantitative reverse transcriptase–PCR analysis. In addition, we performed immunohistochemical analysis of p53, p14
ARF
and the proliferation marker Ki-67. Kaplan–Meier curves and multivariate Cox proportional models were used to study the impact on clinical outcome. Small interfering RNA (siRNA) was used to silence spinophilin and to explore the effects of reduced spinophilin expression on cellular growth.
Results:
In our study, complete loss of spinophilin immunoreactivity was found in 44 of 104 HCCs (42.3%) and reduced levels were found in an additional 37 (35.6%) cases. After adjusting for other prognostic factors, multivariate Cox regression analysis identified low expression of spinophilin as an independent prognostic factor with respect to disease-free (hazard ratio (HR)=1.8; 95% confidence interval (CI)=1.04–3.40;
P
=0.043) and cancer-specific survival (HR=2.0; CI=1.1–3.8;
P
=0.025). Reduced spinophilin expression significantly correlated with higher Ki-67 index in HCC (
P
=0.014). Reducing spinophilin levels by siRNA induced a higher cellular growth rate and increased cyclin D2 expression in tumour cells (
P
<0.05).
Conclusion:
This is the first study of the expression pattern and distribution of spinophilin in HCC. According to our data, the loss of spinophilin is associated with higher proliferation and might be useful as a prognostic marker in patients with HCC.</description><subject>692/699/67/1504/1610</subject><subject>692/699/67/1857</subject><subject>692/699/67/581</subject><subject>692/700/1750</subject><subject>Biological and medical sciences</subject><subject>Biomarkers</subject><subject>Biomarkers, Tumor - metabolism</subject><subject>Biomedical and Life Sciences</subject><subject>Biomedicine</subject><subject>Cancer Research</subject><subject>Carcinoma, Hepatocellular - metabolism</subject><subject>Carcinoma, Hepatocellular - mortality</subject><subject>Cell Line, Tumor</subject><subject>Cell Proliferation</subject><subject>Cyclin D2 - biosynthesis</subject><subject>Disease-Free Survival</subject><subject>Drug Resistance</subject><subject>Epidemiology</subject><subject>Female</subject><subject>Gastroenterology. Liver. Pancreas. Abdomen</subject><subject>Hep G2 Cells</subject><subject>Humans</subject><subject>Internal medicine</subject><subject>Kaplan-Meier Estimate</subject><subject>Ki-67 Antigen - metabolism</subject><subject>Liver cancer</subject><subject>Liver Neoplasms - metabolism</subject><subject>Liver Neoplasms - mortality</subject><subject>Liver. Biliary tract. Portal circulation. Exocrine pancreas</subject><subject>Male</subject><subject>Medical prognosis</subject><subject>Medical sciences</subject><subject>Microfilament Proteins - genetics</subject><subject>Microfilament Proteins - metabolism</subject><subject>Molecular Diagnostics</subject><subject>Molecular Medicine</subject><subject>Multiple tumors. Solid tumors. Tumors in childhood (general aspects)</subject><subject>Nerve Tissue Proteins - genetics</subject><subject>Nerve Tissue Proteins - metabolism</subject><subject>Oncology</subject><subject>Prognosis</subject><subject>Proportional Hazards Models</subject><subject>Proteins</subject><subject>RNA Interference</subject><subject>RNA, Small Interfering</subject><subject>Surveillance</subject><subject>Survival Rate</subject><subject>Tumor Suppressor Protein p14ARF - metabolism</subject><subject>Tumor Suppressor Protein p53 - metabolism</subject><subject>Tumor Suppressor Proteins - genetics</subject><subject>Tumor Suppressor Proteins - metabolism</subject><subject>Tumors</subject><issn>0007-0920</issn><issn>1532-1827</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2013</creationdate><recordtype>article</recordtype><sourceid>C6C</sourceid><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><recordid>eNqNkstu1DAUhi0EosPAjjWyhJBYkMGXOHY2SKjiJo3EpnvLcZyJRxk72ElLX6lP2ZPOUApiwco-Pp_-c_GP0EtKNpRw9b7Z2w0jlG9oJR6hFRWcFVQx-RitCCGyIDUjZ-hZznsIa6LkU3TGuKgprasVutnGK-x-jsnl7GPAscNT7_A4T2bylw5P8yHOCed5vEMiXEcf4tj7wQfsMzbwaL2ZXIuv_NTj3u96l_CY4uA7l44qxsLhp2tsQovHGO_yuxAzCIDMCJQLUz4pOIijdcMwDyZha5KFigfzHD3pzJDdi9O5RhefP12cfy223798O_-4LaygfILZpWvbmhKiusYpRgSVjTKd5WXZdqRlthNUKU4rxi0sxzUNsbJSivC6qR1fow9H2XFuDq610Fgygx6TP5h0raPx-s9M8L3exUvNK6EErH-N3p4EUvwxuzzpg8_LOCa4OGdNeSVLKFf-DyoYk0rUBNDXf6F7-JgAi1goUlNJqhKod0fKpphzct1935ToxS4a7KIXu2iwC-CvHs56D__yBwBvToDJ1gxdMsH6_JuTXMhaLXWLI5chFXYuPejuX4VvAV9w3JQ</recordid><startdate>20130514</startdate><enddate>20130514</enddate><creator>Aigelsreiter, A</creator><creator>Ress, A L</creator><creator>Bettermann, K</creator><creator>Schauer, S</creator><creator>Koller, K</creator><creator>Eisner, F</creator><creator>Kiesslich, T</creator><creator>Stojakovic, T</creator><creator>Samonigg, H</creator><creator>Kornprat, P</creator><creator>Lackner, C</creator><creator>Haybaeck, J</creator><creator>Pichler, M</creator><general>Nature Publishing Group UK</general><general>Nature Publishing Group</general><scope>C6C</scope><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>3V.</scope><scope>7RV</scope><scope>7TO</scope><scope>7U9</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AN0</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>KB0</scope><scope>LK8</scope><scope>M0S</scope><scope>M1P</scope><scope>M7P</scope><scope>NAPCQ</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>20130514</creationdate><title>Low expression of the putative tumour suppressor spinophilin is associated with higher proliferative activity and poor prognosis in patients with hepatocellular carcinoma</title><author>Aigelsreiter, A ; Ress, A L ; Bettermann, K ; Schauer, S ; Koller, K ; Eisner, F ; Kiesslich, T ; Stojakovic, T ; Samonigg, H ; Kornprat, P ; Lackner, C ; Haybaeck, J ; Pichler, M</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c513t-187edd91008fbe820517b8afc344df0d2cf518831623c092ebb0c7688039b9e3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2013</creationdate><topic>692/699/67/1504/1610</topic><topic>692/699/67/1857</topic><topic>692/699/67/581</topic><topic>692/700/1750</topic><topic>Biological and medical sciences</topic><topic>Biomarkers</topic><topic>Biomarkers, Tumor - metabolism</topic><topic>Biomedical and Life Sciences</topic><topic>Biomedicine</topic><topic>Cancer Research</topic><topic>Carcinoma, Hepatocellular - metabolism</topic><topic>Carcinoma, Hepatocellular - mortality</topic><topic>Cell Line, Tumor</topic><topic>Cell Proliferation</topic><topic>Cyclin D2 - biosynthesis</topic><topic>Disease-Free Survival</topic><topic>Drug Resistance</topic><topic>Epidemiology</topic><topic>Female</topic><topic>Gastroenterology. Liver. Pancreas. Abdomen</topic><topic>Hep G2 Cells</topic><topic>Humans</topic><topic>Internal medicine</topic><topic>Kaplan-Meier Estimate</topic><topic>Ki-67 Antigen - metabolism</topic><topic>Liver cancer</topic><topic>Liver Neoplasms - metabolism</topic><topic>Liver Neoplasms - mortality</topic><topic>Liver. Biliary tract. Portal circulation. Exocrine pancreas</topic><topic>Male</topic><topic>Medical prognosis</topic><topic>Medical sciences</topic><topic>Microfilament Proteins - genetics</topic><topic>Microfilament Proteins - metabolism</topic><topic>Molecular Diagnostics</topic><topic>Molecular Medicine</topic><topic>Multiple tumors. Solid tumors. Tumors in childhood (general aspects)</topic><topic>Nerve Tissue Proteins - genetics</topic><topic>Nerve Tissue Proteins - metabolism</topic><topic>Oncology</topic><topic>Prognosis</topic><topic>Proportional Hazards Models</topic><topic>Proteins</topic><topic>RNA Interference</topic><topic>RNA, Small Interfering</topic><topic>Surveillance</topic><topic>Survival Rate</topic><topic>Tumor Suppressor Protein p14ARF - metabolism</topic><topic>Tumor Suppressor Protein p53 - metabolism</topic><topic>Tumor Suppressor Proteins - genetics</topic><topic>Tumor Suppressor Proteins - metabolism</topic><topic>Tumors</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Aigelsreiter, A</creatorcontrib><creatorcontrib>Ress, A L</creatorcontrib><creatorcontrib>Bettermann, K</creatorcontrib><creatorcontrib>Schauer, S</creatorcontrib><creatorcontrib>Koller, K</creatorcontrib><creatorcontrib>Eisner, F</creatorcontrib><creatorcontrib>Kiesslich, T</creatorcontrib><creatorcontrib>Stojakovic, T</creatorcontrib><creatorcontrib>Samonigg, H</creatorcontrib><creatorcontrib>Kornprat, P</creatorcontrib><creatorcontrib>Lackner, C</creatorcontrib><creatorcontrib>Haybaeck, J</creatorcontrib><creatorcontrib>Pichler, M</creatorcontrib><collection>Springer Nature OA/Free Journals</collection><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>ProQuest Central (Corporate)</collection><collection>Nursing & Allied Health Database</collection><collection>Oncogenes and Growth Factors Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>Public Health Database</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>British Nursing Database</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Natural Science Collection</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Nursing & Allied Health Database (Alumni Edition)</collection><collection>ProQuest Biological Science Collection</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Biological Science Database</collection><collection>Nursing & Allied Health Premium</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>British journal of cancer</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Aigelsreiter, A</au><au>Ress, A L</au><au>Bettermann, K</au><au>Schauer, S</au><au>Koller, K</au><au>Eisner, F</au><au>Kiesslich, T</au><au>Stojakovic, T</au><au>Samonigg, H</au><au>Kornprat, P</au><au>Lackner, C</au><au>Haybaeck, J</au><au>Pichler, M</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Low expression of the putative tumour suppressor spinophilin is associated with higher proliferative activity and poor prognosis in patients with hepatocellular carcinoma</atitle><jtitle>British journal of cancer</jtitle><stitle>Br J Cancer</stitle><addtitle>Br J Cancer</addtitle><date>2013-05-14</date><risdate>2013</risdate><volume>108</volume><issue>9</issue><spage>1830</spage><epage>1837</epage><pages>1830-1837</pages><issn>0007-0920</issn><eissn>1532-1827</eissn><coden>BJCAAI</coden><abstract>Background:
Spinophilin, a multifunctional intracellular scaffold protein, is reduced in certain types of cancer and is regarded as a novel putative tumour suppressor protein. However, the role of spinophilin in hepatocellular carcinoma (HCC) has never been explored before.
Methods:
In this study, we determined for the first time the expression pattern of spinophilin in human HCC by immunohistochemistry and quantitative reverse transcriptase–PCR analysis. In addition, we performed immunohistochemical analysis of p53, p14
ARF
and the proliferation marker Ki-67. Kaplan–Meier curves and multivariate Cox proportional models were used to study the impact on clinical outcome. Small interfering RNA (siRNA) was used to silence spinophilin and to explore the effects of reduced spinophilin expression on cellular growth.
Results:
In our study, complete loss of spinophilin immunoreactivity was found in 44 of 104 HCCs (42.3%) and reduced levels were found in an additional 37 (35.6%) cases. After adjusting for other prognostic factors, multivariate Cox regression analysis identified low expression of spinophilin as an independent prognostic factor with respect to disease-free (hazard ratio (HR)=1.8; 95% confidence interval (CI)=1.04–3.40;
P
=0.043) and cancer-specific survival (HR=2.0; CI=1.1–3.8;
P
=0.025). Reduced spinophilin expression significantly correlated with higher Ki-67 index in HCC (
P
=0.014). Reducing spinophilin levels by siRNA induced a higher cellular growth rate and increased cyclin D2 expression in tumour cells (
P
<0.05).
Conclusion:
This is the first study of the expression pattern and distribution of spinophilin in HCC. According to our data, the loss of spinophilin is associated with higher proliferation and might be useful as a prognostic marker in patients with HCC.</abstract><cop>London</cop><pub>Nature Publishing Group UK</pub><pmid>23591196</pmid><doi>10.1038/bjc.2013.165</doi><tpages>8</tpages><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0007-0920 |
| ispartof | British journal of cancer, 2013-05, Vol.108 (9), p.1830-1837 |
| issn | 0007-0920 1532-1827 |
| language | eng |
| recordid | cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_3658515 |
| source | MEDLINE; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; Nature Journals Online; PubMed Central |
| subjects | 692/699/67/1504/1610 692/699/67/1857 692/699/67/581 692/700/1750 Biological and medical sciences Biomarkers Biomarkers, Tumor - metabolism Biomedical and Life Sciences Biomedicine Cancer Research Carcinoma, Hepatocellular - metabolism Carcinoma, Hepatocellular - mortality Cell Line, Tumor Cell Proliferation Cyclin D2 - biosynthesis Disease-Free Survival Drug Resistance Epidemiology Female Gastroenterology. Liver. Pancreas. Abdomen Hep G2 Cells Humans Internal medicine Kaplan-Meier Estimate Ki-67 Antigen - metabolism Liver cancer Liver Neoplasms - metabolism Liver Neoplasms - mortality Liver. Biliary tract. Portal circulation. Exocrine pancreas Male Medical prognosis Medical sciences Microfilament Proteins - genetics Microfilament Proteins - metabolism Molecular Diagnostics Molecular Medicine Multiple tumors. Solid tumors. Tumors in childhood (general aspects) Nerve Tissue Proteins - genetics Nerve Tissue Proteins - metabolism Oncology Prognosis Proportional Hazards Models Proteins RNA Interference RNA, Small Interfering Surveillance Survival Rate Tumor Suppressor Protein p14ARF - metabolism Tumor Suppressor Protein p53 - metabolism Tumor Suppressor Proteins - genetics Tumor Suppressor Proteins - metabolism Tumors |
| title | Low expression of the putative tumour suppressor spinophilin is associated with higher proliferative activity and poor prognosis in patients with hepatocellular carcinoma |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2024-12-04T23%3A08%3A34IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_pubme&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Low%20expression%20of%20the%20putative%20tumour%20suppressor%20spinophilin%20is%20associated%20with%20higher%20proliferative%20activity%20and%20poor%20prognosis%20in%20patients%20with%20hepatocellular%20carcinoma&rft.jtitle=British%20journal%20of%20cancer&rft.au=Aigelsreiter,%20A&rft.date=2013-05-14&rft.volume=108&rft.issue=9&rft.spage=1830&rft.epage=1837&rft.pages=1830-1837&rft.issn=0007-0920&rft.eissn=1532-1827&rft.coden=BJCAAI&rft_id=info:doi/10.1038/bjc.2013.165&rft_dat=%3Cproquest_pubme%3E1367488045%3C/proquest_pubme%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=1350917064&rft_id=info:pmid/23591196&rfr_iscdi=true |