Epithelial Membrane Protein 2 Is a Prognostic Indictor for Patients with Urothelial Carcinoma of the Upper Urinary Tract
Upper urinary tract urothelial carcinoma is a relatively uncommon disease and is diagnosed more frequently at advanced stages. The prognosis of these patients mainly has been related to tumor stage and grade. As a result, the definition of prognostic indicators enabling precise patient selection is...
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| Veröffentlicht in: | The American journal of pathology 2013-09, Vol.183 (3), p.709-719 |
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| creator | Wang, Yi-Wen Li, Wei-Ming Wu, Wen-Jeng Chai, Chee-Yin Chang, Tsuey-Yu Sun, Yin Cheng, Chih-Jen Shiue, Yow-Ling Su, Shu-Jem Cheng, Hong-Lin Liu, Hsiao-Sheng Chow, Nan-Haw |
| description | Upper urinary tract urothelial carcinoma is a relatively uncommon disease and is diagnosed more frequently at advanced stages. The prognosis of these patients mainly has been related to tumor stage and grade. As a result, the definition of prognostic indicators enabling precise patient selection is mandatory for neoadjuvant or adjuvant therapies. The epithelial membrane protein (EMP2) was identified as one of the up-regulated genes by isoflavones. EMP2 overexpression suppressed foci formation, anchorage-independent growth in vitro , and tumorigenicity in severe combined immunodeficiency mice (all P < 0.05). In addition, a cross-talk between EMP2 and integrins αV and β3 was shown in the regulation of cell adhesion and migration. Higher EMP2 expression was associated with a better progression-free survival ( P = 0.008) and cancer-related death ( P < 0.001). EMP2 was identified as a tumor-suppressor gene in urinary tract urothelial carcinoma and may be an innovative co-targeting candidate for designing integrin-based cancer therapy. |
| doi_str_mv | 10.1016/j.ajpath.2013.05.015 |
| format | Article |
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The prognosis of these patients mainly has been related to tumor stage and grade. As a result, the definition of prognostic indicators enabling precise patient selection is mandatory for neoadjuvant or adjuvant therapies. The epithelial membrane protein (EMP2) was identified as one of the up-regulated genes by isoflavones. EMP2 overexpression suppressed foci formation, anchorage-independent growth in vitro , and tumorigenicity in severe combined immunodeficiency mice (all P < 0.05). In addition, a cross-talk between EMP2 and integrins αV and β3 was shown in the regulation of cell adhesion and migration. Higher EMP2 expression was associated with a better progression-free survival ( P = 0.008) and cancer-related death ( P < 0.001). EMP2 was identified as a tumor-suppressor gene in urinary tract urothelial carcinoma and may be an innovative co-targeting candidate for designing integrin-based cancer therapy.</description><identifier>ISSN: 0002-9440</identifier><identifier>EISSN: 1525-2191</identifier><identifier>DOI: 10.1016/j.ajpath.2013.05.015</identifier><identifier>PMID: 23838430</identifier><language>eng</language><publisher>United States: Elsevier Inc</publisher><subject>Adult ; Aged ; Aged, 80 and over ; Animals ; Carcinogenesis - drug effects ; Carcinogenesis - metabolism ; Carcinogenesis - pathology ; Cell Adhesion - drug effects ; Cell Line, Tumor ; Cell Movement - drug effects ; Cell Proliferation - drug effects ; Epithelial Cells - drug effects ; Epithelial Cells - metabolism ; Epithelial Cells - pathology ; Female ; Gene Expression Regulation, Neoplastic - drug effects ; HEK293 Cells ; Humans ; Integrins - metabolism ; Isoflavones - pharmacology ; Male ; Membrane Glycoproteins - genetics ; Membrane Glycoproteins - metabolism ; Mice ; Middle Aged ; Pathology ; Prognosis ; Proportional Hazards Models ; Protein Transport - drug effects ; Urologic Neoplasms - genetics ; Urologic Neoplasms - metabolism ; Urologic Neoplasms - pathology ; Urothelium - drug effects ; Urothelium - metabolism ; Urothelium - pathology ; Young Adult</subject><ispartof>The American journal of pathology, 2013-09, Vol.183 (3), p.709-719</ispartof><rights>American Society for Investigative Pathology</rights><rights>2013 American Society for Investigative Pathology</rights><rights>Copyright © 2013 American Society for Investigative Pathology. Published by Elsevier Inc. 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The prognosis of these patients mainly has been related to tumor stage and grade. As a result, the definition of prognostic indicators enabling precise patient selection is mandatory for neoadjuvant or adjuvant therapies. The epithelial membrane protein (EMP2) was identified as one of the up-regulated genes by isoflavones. EMP2 overexpression suppressed foci formation, anchorage-independent growth in vitro , and tumorigenicity in severe combined immunodeficiency mice (all P < 0.05). In addition, a cross-talk between EMP2 and integrins αV and β3 was shown in the regulation of cell adhesion and migration. Higher EMP2 expression was associated with a better progression-free survival ( P = 0.008) and cancer-related death ( P < 0.001). EMP2 was identified as a tumor-suppressor gene in urinary tract urothelial carcinoma and may be an innovative co-targeting candidate for designing integrin-based cancer therapy.</description><subject>Adult</subject><subject>Aged</subject><subject>Aged, 80 and over</subject><subject>Animals</subject><subject>Carcinogenesis - drug effects</subject><subject>Carcinogenesis - metabolism</subject><subject>Carcinogenesis - pathology</subject><subject>Cell Adhesion - drug effects</subject><subject>Cell Line, Tumor</subject><subject>Cell Movement - drug effects</subject><subject>Cell Proliferation - drug effects</subject><subject>Epithelial Cells - drug effects</subject><subject>Epithelial Cells - metabolism</subject><subject>Epithelial Cells - pathology</subject><subject>Female</subject><subject>Gene Expression Regulation, Neoplastic - drug effects</subject><subject>HEK293 Cells</subject><subject>Humans</subject><subject>Integrins - metabolism</subject><subject>Isoflavones - pharmacology</subject><subject>Male</subject><subject>Membrane Glycoproteins - genetics</subject><subject>Membrane Glycoproteins - metabolism</subject><subject>Mice</subject><subject>Middle Aged</subject><subject>Pathology</subject><subject>Prognosis</subject><subject>Proportional Hazards Models</subject><subject>Protein Transport - drug effects</subject><subject>Urologic Neoplasms - genetics</subject><subject>Urologic Neoplasms - metabolism</subject><subject>Urologic Neoplasms - pathology</subject><subject>Urothelium - drug effects</subject><subject>Urothelium - metabolism</subject><subject>Urothelium - pathology</subject><subject>Young Adult</subject><issn>0002-9440</issn><issn>1525-2191</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2013</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkU-P0zAQxS0EYsvCN0DIRy4J4z9J3QsSqhaotIiV2ErcLNuZsA5pHGx3Yb89jlo4cOFgW2O998bzMyEvGdQMWPtmqM0wm3xXc2CihqYG1jwiK9bwpuJswx6TFQDwaiMlXJBnKQ2lbIWCp-SCCyWUFLAiv65mn-9w9Gakn_Bgo5mQ3sSQ0U-U012iZim_TSFl7-hu6rzLIdK-rBuTPU450Z8lgu6L6Ry0NdH5KRwMDT0tl3Q_zxiLwk8mPtDbaFx-Tp70Zkz44nxekv37q9vtx-r684fd9t115WQrcuUauXENNxZayyyHtV0Dt4pzjkZ2RihrwViFXPQI0nZK9IxL1zvbdqqYxSV5fcqdY_hxxJT1wSeH41gGDcekmeSKr2GtoEjlSepiSClir-foD-XFmoFemOtBn5jrhbmGRhfmxfbq3OFoD9j9Nf2BXARvTwIsc957jDq5As5h5yO6rLvg_9fh3wA3-sk7M37HB0xDOMapMNRMJ65Bf1n-ffl2JgDK_lX8BsiBqk8</recordid><startdate>20130901</startdate><enddate>20130901</enddate><creator>Wang, Yi-Wen</creator><creator>Li, Wei-Ming</creator><creator>Wu, Wen-Jeng</creator><creator>Chai, Chee-Yin</creator><creator>Chang, Tsuey-Yu</creator><creator>Sun, Yin</creator><creator>Cheng, Chih-Jen</creator><creator>Shiue, Yow-Ling</creator><creator>Su, Shu-Jem</creator><creator>Cheng, Hong-Lin</creator><creator>Liu, Hsiao-Sheng</creator><creator>Chow, Nan-Haw</creator><general>Elsevier Inc</general><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>20130901</creationdate><title>Epithelial Membrane Protein 2 Is a Prognostic Indictor for Patients with Urothelial Carcinoma of the Upper Urinary Tract</title><author>Wang, Yi-Wen ; Li, Wei-Ming ; Wu, Wen-Jeng ; Chai, Chee-Yin ; Chang, Tsuey-Yu ; Sun, Yin ; Cheng, Chih-Jen ; Shiue, Yow-Ling ; Su, Shu-Jem ; Cheng, Hong-Lin ; Liu, Hsiao-Sheng ; Chow, Nan-Haw</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c463t-c549c52ab06b1b207b702b8222ea4da38bb0ab8e23fe04bd83f124cfcb6d8c543</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2013</creationdate><topic>Adult</topic><topic>Aged</topic><topic>Aged, 80 and over</topic><topic>Animals</topic><topic>Carcinogenesis - drug effects</topic><topic>Carcinogenesis - metabolism</topic><topic>Carcinogenesis - pathology</topic><topic>Cell Adhesion - drug effects</topic><topic>Cell Line, Tumor</topic><topic>Cell Movement - drug effects</topic><topic>Cell Proliferation - drug effects</topic><topic>Epithelial Cells - drug effects</topic><topic>Epithelial Cells - metabolism</topic><topic>Epithelial Cells - pathology</topic><topic>Female</topic><topic>Gene Expression Regulation, Neoplastic - drug effects</topic><topic>HEK293 Cells</topic><topic>Humans</topic><topic>Integrins - metabolism</topic><topic>Isoflavones - pharmacology</topic><topic>Male</topic><topic>Membrane Glycoproteins - genetics</topic><topic>Membrane Glycoproteins - metabolism</topic><topic>Mice</topic><topic>Middle Aged</topic><topic>Pathology</topic><topic>Prognosis</topic><topic>Proportional Hazards Models</topic><topic>Protein Transport - drug effects</topic><topic>Urologic Neoplasms - genetics</topic><topic>Urologic Neoplasms - metabolism</topic><topic>Urologic Neoplasms - pathology</topic><topic>Urothelium - drug effects</topic><topic>Urothelium - metabolism</topic><topic>Urothelium - pathology</topic><topic>Young Adult</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Wang, Yi-Wen</creatorcontrib><creatorcontrib>Li, Wei-Ming</creatorcontrib><creatorcontrib>Wu, Wen-Jeng</creatorcontrib><creatorcontrib>Chai, Chee-Yin</creatorcontrib><creatorcontrib>Chang, Tsuey-Yu</creatorcontrib><creatorcontrib>Sun, Yin</creatorcontrib><creatorcontrib>Cheng, Chih-Jen</creatorcontrib><creatorcontrib>Shiue, Yow-Ling</creatorcontrib><creatorcontrib>Su, Shu-Jem</creatorcontrib><creatorcontrib>Cheng, Hong-Lin</creatorcontrib><creatorcontrib>Liu, Hsiao-Sheng</creatorcontrib><creatorcontrib>Chow, Nan-Haw</creatorcontrib><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>The American journal of pathology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Wang, Yi-Wen</au><au>Li, Wei-Ming</au><au>Wu, Wen-Jeng</au><au>Chai, Chee-Yin</au><au>Chang, Tsuey-Yu</au><au>Sun, Yin</au><au>Cheng, Chih-Jen</au><au>Shiue, Yow-Ling</au><au>Su, Shu-Jem</au><au>Cheng, Hong-Lin</au><au>Liu, Hsiao-Sheng</au><au>Chow, Nan-Haw</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Epithelial Membrane Protein 2 Is a Prognostic Indictor for Patients with Urothelial Carcinoma of the Upper Urinary Tract</atitle><jtitle>The American journal of pathology</jtitle><addtitle>Am J Pathol</addtitle><date>2013-09-01</date><risdate>2013</risdate><volume>183</volume><issue>3</issue><spage>709</spage><epage>719</epage><pages>709-719</pages><issn>0002-9440</issn><eissn>1525-2191</eissn><abstract>Upper urinary tract urothelial carcinoma is a relatively uncommon disease and is diagnosed more frequently at advanced stages. The prognosis of these patients mainly has been related to tumor stage and grade. As a result, the definition of prognostic indicators enabling precise patient selection is mandatory for neoadjuvant or adjuvant therapies. The epithelial membrane protein (EMP2) was identified as one of the up-regulated genes by isoflavones. EMP2 overexpression suppressed foci formation, anchorage-independent growth in vitro , and tumorigenicity in severe combined immunodeficiency mice (all P < 0.05). In addition, a cross-talk between EMP2 and integrins αV and β3 was shown in the regulation of cell adhesion and migration. Higher EMP2 expression was associated with a better progression-free survival ( P = 0.008) and cancer-related death ( P < 0.001). 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| subjects | Adult Aged Aged, 80 and over Animals Carcinogenesis - drug effects Carcinogenesis - metabolism Carcinogenesis - pathology Cell Adhesion - drug effects Cell Line, Tumor Cell Movement - drug effects Cell Proliferation - drug effects Epithelial Cells - drug effects Epithelial Cells - metabolism Epithelial Cells - pathology Female Gene Expression Regulation, Neoplastic - drug effects HEK293 Cells Humans Integrins - metabolism Isoflavones - pharmacology Male Membrane Glycoproteins - genetics Membrane Glycoproteins - metabolism Mice Middle Aged Pathology Prognosis Proportional Hazards Models Protein Transport - drug effects Urologic Neoplasms - genetics Urologic Neoplasms - metabolism Urologic Neoplasms - pathology Urothelium - drug effects Urothelium - metabolism Urothelium - pathology Young Adult |
| title | Epithelial Membrane Protein 2 Is a Prognostic Indictor for Patients with Urothelial Carcinoma of the Upper Urinary Tract |
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