Vasodilator-Stimulated Phosphoprotein Biomarkers Are Associated with Invasion and Metastasis in Colorectal Cancer
Background and Aims: The benefit of adjuvant chemotherapy for stage II colorectal cancer (CRC) patients remains unclear, emphasizing the need for improved prognostic biomarkers to identify patients at risk of metastatic recurrence. To address this unmet clinical need, we examined the expression and...
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creator | Pitari, Giovanni M Cotzia, Paolo Ali, Mehboob Birbe, Ruth Rizzo, Wendy Bombonati, Alessandro Palazzo, Juan Solomides, Charalambos Shuber, Anthony P Sinicrope, Frank A Zuzga, David S |
description | Background and Aims:
The benefit of adjuvant chemotherapy for stage II colorectal cancer (CRC) patients remains unclear, emphasizing the need for improved prognostic biomarkers to identify patients at risk of metastatic recurrence. To address this unmet clinical need, we examined the expression and phosphorylation status of the vasodilator-stimulated phosphoprotein (VASP) in CRC tumor progression. VASP, a processive actin polymerase, promotes the formation of invasive membrane structures leading to extracellular matrix remodeling and tumor invasion. Phosphorylation of VASP serine (Ser) residues 157 and 239 regulate VASP function, directing subcellular localization and inhibiting actin polymerization, respectively.
Methods:
The expression levels of VASP protein, pSer157-VASP, and pSer239-VASP were determined by immunohistochemistry in tumors and matched normal adjacent tissue from 141 CRC patients, divided into 2 cohorts, and the association of VASP biomarker expression with clinicopathologic features and disease recurrence was examined.
Results:
We report that changes in VASP expression and phosphorylation were significantly associated with tumor invasion and disease recurrence. Furthermore, we disclose a novel 2-tiered methodology to maximize VASP positive and negative predictive value performance for prognostication.
Conclusion:
VASP biomarkers may serve as prognostic biomarkers in CRC and should be evaluated in a larger clinical study. |
doi_str_mv | 10.1177/1179299X18774551 |
format | Article |
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The benefit of adjuvant chemotherapy for stage II colorectal cancer (CRC) patients remains unclear, emphasizing the need for improved prognostic biomarkers to identify patients at risk of metastatic recurrence. To address this unmet clinical need, we examined the expression and phosphorylation status of the vasodilator-stimulated phosphoprotein (VASP) in CRC tumor progression. VASP, a processive actin polymerase, promotes the formation of invasive membrane structures leading to extracellular matrix remodeling and tumor invasion. Phosphorylation of VASP serine (Ser) residues 157 and 239 regulate VASP function, directing subcellular localization and inhibiting actin polymerization, respectively.
Methods:
The expression levels of VASP protein, pSer157-VASP, and pSer239-VASP were determined by immunohistochemistry in tumors and matched normal adjacent tissue from 141 CRC patients, divided into 2 cohorts, and the association of VASP biomarker expression with clinicopathologic features and disease recurrence was examined.
Results:
We report that changes in VASP expression and phosphorylation were significantly associated with tumor invasion and disease recurrence. Furthermore, we disclose a novel 2-tiered methodology to maximize VASP positive and negative predictive value performance for prognostication.
Conclusion:
VASP biomarkers may serve as prognostic biomarkers in CRC and should be evaluated in a larger clinical study.</description><identifier>ISSN: 1179-299X</identifier><identifier>EISSN: 1179-299X</identifier><identifier>DOI: 10.1177/1179299X18774551</identifier><identifier>PMID: 30911223</identifier><language>eng</language><publisher>London, England: SAGE Publications</publisher><subject>Actin ; Authorship ; Biomarkers ; Chemotherapy ; Colorectal cancer ; Colorectal carcinoma ; Extracellular matrix ; Immunohistochemistry ; Invasiveness ; Localization ; Lymphatic system ; Medical research ; Metastases ; Metastasis ; Patients ; Phosphorylation ; Polymerization ; Rapid Communication ; Serine ; Stockholders ; Studies ; Tumors ; Vasodilator-stimulated phosphoprotein</subject><ispartof>Biomarkers in cancer, 2018, Vol.10, p.1179299X18774551</ispartof><rights>The Author(s) 2018</rights><rights>The Author(s) 2018 2018 SAGE Publications Ltd unless otherwise noted. Manuscript content on this site is licensed under Creative Commons Licenses</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c3071-712175eb56e06e06707e1e534a88cc7ff31869793a89613b8e261071943cd563</citedby><cites>FETCH-LOGICAL-c3071-712175eb56e06e06707e1e534a88cc7ff31869793a89613b8e261071943cd563</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/PMC6419247/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC6419247/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,724,777,781,882,4011,27905,27906,27907,53773,53775</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/30911223$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Pitari, Giovanni M</creatorcontrib><creatorcontrib>Cotzia, Paolo</creatorcontrib><creatorcontrib>Ali, Mehboob</creatorcontrib><creatorcontrib>Birbe, Ruth</creatorcontrib><creatorcontrib>Rizzo, Wendy</creatorcontrib><creatorcontrib>Bombonati, Alessandro</creatorcontrib><creatorcontrib>Palazzo, Juan</creatorcontrib><creatorcontrib>Solomides, Charalambos</creatorcontrib><creatorcontrib>Shuber, Anthony P</creatorcontrib><creatorcontrib>Sinicrope, Frank A</creatorcontrib><creatorcontrib>Zuzga, David S</creatorcontrib><title>Vasodilator-Stimulated Phosphoprotein Biomarkers Are Associated with Invasion and Metastasis in Colorectal Cancer</title><title>Biomarkers in cancer</title><addtitle>Biomark Cancer</addtitle><description>Background and Aims:
The benefit of adjuvant chemotherapy for stage II colorectal cancer (CRC) patients remains unclear, emphasizing the need for improved prognostic biomarkers to identify patients at risk of metastatic recurrence. To address this unmet clinical need, we examined the expression and phosphorylation status of the vasodilator-stimulated phosphoprotein (VASP) in CRC tumor progression. VASP, a processive actin polymerase, promotes the formation of invasive membrane structures leading to extracellular matrix remodeling and tumor invasion. Phosphorylation of VASP serine (Ser) residues 157 and 239 regulate VASP function, directing subcellular localization and inhibiting actin polymerization, respectively.
Methods:
The expression levels of VASP protein, pSer157-VASP, and pSer239-VASP were determined by immunohistochemistry in tumors and matched normal adjacent tissue from 141 CRC patients, divided into 2 cohorts, and the association of VASP biomarker expression with clinicopathologic features and disease recurrence was examined.
Results:
We report that changes in VASP expression and phosphorylation were significantly associated with tumor invasion and disease recurrence. Furthermore, we disclose a novel 2-tiered methodology to maximize VASP positive and negative predictive value performance for prognostication.
Conclusion:
VASP biomarkers may serve as prognostic biomarkers in CRC and should be evaluated in a larger clinical study.</description><subject>Actin</subject><subject>Authorship</subject><subject>Biomarkers</subject><subject>Chemotherapy</subject><subject>Colorectal cancer</subject><subject>Colorectal carcinoma</subject><subject>Extracellular matrix</subject><subject>Immunohistochemistry</subject><subject>Invasiveness</subject><subject>Localization</subject><subject>Lymphatic system</subject><subject>Medical research</subject><subject>Metastases</subject><subject>Metastasis</subject><subject>Patients</subject><subject>Phosphorylation</subject><subject>Polymerization</subject><subject>Rapid Communication</subject><subject>Serine</subject><subject>Stockholders</subject><subject>Studies</subject><subject>Tumors</subject><subject>Vasodilator-stimulated phosphoprotein</subject><issn>1179-299X</issn><issn>1179-299X</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2018</creationdate><recordtype>article</recordtype><sourceid>AFRWT</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><recordid>eNp1kd9rHCEQx6UkNOGa9z4VoS952dbR3VVfAtejaQMpCTSUvonnzuVM9_Siuyn57-v18hsigw76-X51HELeA_sEIOXnMmmu9W9QUtZNA2_I_mar2uztPMn3yEHOV6yMmoFumrdkTzANwLnYJ9e_bI6d7-0QU_Vz8KuxpNjR82XM62VcpzigD_SLjyub_mDKdJqQTnOOzv8H__phSU_Cjc0-BmpDR3_gYHMJn2lRzmIfE7rB9nRmg8P0juwubJ_x4G6dkIvjrxez79Xp2beT2fS0coJJqCRwkA3OmxbZJiSTCNiI2irlnFwsBKhWSy2s0i2IuULeQhHqWriuacWEHG1t1-N8hZ3DMCTbm3XypZBbE603z0-CX5rLeGPaGjSvZTE4vDNI8XrEPJiVzw773gaMYzYctFS65uUbJ-TjC_QqjimU6grVKsUZU3Wh2JZyKeaccPHwGGBm01HzsqNF8uFpEQ-C-_4VoNoC2V7i462vGv4DuhSpdQ</recordid><startdate>2018</startdate><enddate>2018</enddate><creator>Pitari, Giovanni M</creator><creator>Cotzia, Paolo</creator><creator>Ali, Mehboob</creator><creator>Birbe, Ruth</creator><creator>Rizzo, Wendy</creator><creator>Bombonati, Alessandro</creator><creator>Palazzo, Juan</creator><creator>Solomides, Charalambos</creator><creator>Shuber, Anthony P</creator><creator>Sinicrope, Frank A</creator><creator>Zuzga, David S</creator><general>SAGE Publications</general><general>Sage Publications Ltd</general><scope>AFRWT</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7T5</scope><scope>7TO</scope><scope>8FE</scope><scope>8FH</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AYAGU</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>GNUQQ</scope><scope>H94</scope><scope>HCIFZ</scope><scope>LK8</scope><scope>M7P</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>2018</creationdate><title>Vasodilator-Stimulated Phosphoprotein Biomarkers Are Associated with Invasion and Metastasis in Colorectal Cancer</title><author>Pitari, Giovanni M ; Cotzia, Paolo ; Ali, Mehboob ; Birbe, Ruth ; Rizzo, Wendy ; Bombonati, Alessandro ; Palazzo, Juan ; Solomides, Charalambos ; Shuber, Anthony P ; Sinicrope, Frank A ; Zuzga, David S</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c3071-712175eb56e06e06707e1e534a88cc7ff31869793a89613b8e261071943cd563</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2018</creationdate><topic>Actin</topic><topic>Authorship</topic><topic>Biomarkers</topic><topic>Chemotherapy</topic><topic>Colorectal cancer</topic><topic>Colorectal carcinoma</topic><topic>Extracellular matrix</topic><topic>Immunohistochemistry</topic><topic>Invasiveness</topic><topic>Localization</topic><topic>Lymphatic system</topic><topic>Medical research</topic><topic>Metastases</topic><topic>Metastasis</topic><topic>Patients</topic><topic>Phosphorylation</topic><topic>Polymerization</topic><topic>Rapid Communication</topic><topic>Serine</topic><topic>Stockholders</topic><topic>Studies</topic><topic>Tumors</topic><topic>Vasodilator-stimulated phosphoprotein</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Pitari, Giovanni M</creatorcontrib><creatorcontrib>Cotzia, Paolo</creatorcontrib><creatorcontrib>Ali, Mehboob</creatorcontrib><creatorcontrib>Birbe, Ruth</creatorcontrib><creatorcontrib>Rizzo, Wendy</creatorcontrib><creatorcontrib>Bombonati, Alessandro</creatorcontrib><creatorcontrib>Palazzo, Juan</creatorcontrib><creatorcontrib>Solomides, Charalambos</creatorcontrib><creatorcontrib>Shuber, Anthony P</creatorcontrib><creatorcontrib>Sinicrope, Frank A</creatorcontrib><creatorcontrib>Zuzga, David S</creatorcontrib><collection>Sage Journals GOLD Open Access 2024</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Immunology Abstracts</collection><collection>Oncogenes and Growth Factors Abstracts</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>Australia & New Zealand 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>ProQuest Central Student</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Biological Science Collection</collection><collection>Biological Science Database</collection><collection>Publicly Available Content Database</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>Biomarkers in cancer</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Pitari, Giovanni M</au><au>Cotzia, Paolo</au><au>Ali, Mehboob</au><au>Birbe, Ruth</au><au>Rizzo, Wendy</au><au>Bombonati, Alessandro</au><au>Palazzo, Juan</au><au>Solomides, Charalambos</au><au>Shuber, Anthony P</au><au>Sinicrope, Frank A</au><au>Zuzga, David S</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Vasodilator-Stimulated Phosphoprotein Biomarkers Are Associated with Invasion and Metastasis in Colorectal Cancer</atitle><jtitle>Biomarkers in cancer</jtitle><addtitle>Biomark Cancer</addtitle><date>2018</date><risdate>2018</risdate><volume>10</volume><spage>1179299X18774551</spage><pages>1179299X18774551-</pages><issn>1179-299X</issn><eissn>1179-299X</eissn><abstract>Background and Aims:
The benefit of adjuvant chemotherapy for stage II colorectal cancer (CRC) patients remains unclear, emphasizing the need for improved prognostic biomarkers to identify patients at risk of metastatic recurrence. To address this unmet clinical need, we examined the expression and phosphorylation status of the vasodilator-stimulated phosphoprotein (VASP) in CRC tumor progression. VASP, a processive actin polymerase, promotes the formation of invasive membrane structures leading to extracellular matrix remodeling and tumor invasion. Phosphorylation of VASP serine (Ser) residues 157 and 239 regulate VASP function, directing subcellular localization and inhibiting actin polymerization, respectively.
Methods:
The expression levels of VASP protein, pSer157-VASP, and pSer239-VASP were determined by immunohistochemistry in tumors and matched normal adjacent tissue from 141 CRC patients, divided into 2 cohorts, and the association of VASP biomarker expression with clinicopathologic features and disease recurrence was examined.
Results:
We report that changes in VASP expression and phosphorylation were significantly associated with tumor invasion and disease recurrence. Furthermore, we disclose a novel 2-tiered methodology to maximize VASP positive and negative predictive value performance for prognostication.
Conclusion:
VASP biomarkers may serve as prognostic biomarkers in CRC and should be evaluated in a larger clinical study.</abstract><cop>London, England</cop><pub>SAGE Publications</pub><pmid>30911223</pmid><doi>10.1177/1179299X18774551</doi><oa>free_for_read</oa></addata></record> |
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subjects | Actin Authorship Biomarkers Chemotherapy Colorectal cancer Colorectal carcinoma Extracellular matrix Immunohistochemistry Invasiveness Localization Lymphatic system Medical research Metastases Metastasis Patients Phosphorylation Polymerization Rapid Communication Serine Stockholders Studies Tumors Vasodilator-stimulated phosphoprotein |
title | Vasodilator-Stimulated Phosphoprotein Biomarkers Are Associated with Invasion and Metastasis in Colorectal Cancer |
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