Comparative and Targeted Proteomic Analyses of Urinary Microparticles from Bladder Cancer and Hernia Patients
Bladder cancer is a common urologic cancer whose incidence continues to rise annually. Urinary microparticles are an attractive material for noninvasive bladder cancer biomarker discovery. In this study, we applied isotopic dimethylation labeling coupled with liquid chromatography-tandem mass spectr...
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| Veröffentlicht in: | Journal of proteome research 2012-12, Vol.11 (12), p.5611-5629 |
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| creator | Chen, Chien-Lun Lai, Yue-Fan Tang, Petrus Chien, Kun-Yi Yu, Jau-Song Tsai, Cheng-Han Chen, Hsiao-Wei Wu, Chih-Ching Chung, Ting Hsu, Chia-Wei Chen, Chi-De Chang, Yu-Sun Chang, Phei-Lang Chen, Yi-Ting |
| description | Bladder cancer is a common urologic cancer whose incidence continues to rise annually. Urinary microparticles are an attractive material for noninvasive bladder cancer biomarker discovery. In this study, we applied isotopic dimethylation labeling coupled with liquid chromatography-tandem mass spectrometry (LC–MS/MS) to discover bladder cancer biomarkers in urinary microparticles isolated from hernia (control) and bladder cancer patients. This approach identified 2964 proteins based on more than two distinct peptides, of which 2058 had not previously been reported as constituents of human urine exosomes/microparticles. A total of 107 differentially expressed proteins were identified as candidate biomarkers. Differences in the concentrations of 29 proteins (41 signature peptides) were precisely quantified by LC–MRM/MS in 48 urine samples of bladder cancer, hernia, and urinary tract infection/hematuria. Concentrations of 24 proteins changed significantly (p < 0.05) between bladder cancer (n = 28) and hernia (n = 12), with area-under-the-curve values ranging from 0.702 to 0.896. Finally, we quantified tumor-associated calcium-signal transducer 2 (TACSTD2) in raw urine specimens (n = 221) using a commercial ELISA and confirmed its potential value for diagnosis of bladder cancer. Our study reveals a strong association of TACSTD2 with bladder cancer and highlights the potential of human urinary microparticles in the noninvasive diagnosis of bladder cancer. |
| doi_str_mv | 10.1021/pr3008732 |
| format | Article |
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Urinary microparticles are an attractive material for noninvasive bladder cancer biomarker discovery. In this study, we applied isotopic dimethylation labeling coupled with liquid chromatography-tandem mass spectrometry (LC–MS/MS) to discover bladder cancer biomarkers in urinary microparticles isolated from hernia (control) and bladder cancer patients. This approach identified 2964 proteins based on more than two distinct peptides, of which 2058 had not previously been reported as constituents of human urine exosomes/microparticles. A total of 107 differentially expressed proteins were identified as candidate biomarkers. Differences in the concentrations of 29 proteins (41 signature peptides) were precisely quantified by LC–MRM/MS in 48 urine samples of bladder cancer, hernia, and urinary tract infection/hematuria. Concentrations of 24 proteins changed significantly (p < 0.05) between bladder cancer (n = 28) and hernia (n = 12), with area-under-the-curve values ranging from 0.702 to 0.896. Finally, we quantified tumor-associated calcium-signal transducer 2 (TACSTD2) in raw urine specimens (n = 221) using a commercial ELISA and confirmed its potential value for diagnosis of bladder cancer. Our study reveals a strong association of TACSTD2 with bladder cancer and highlights the potential of human urinary microparticles in the noninvasive diagnosis of bladder cancer.</description><identifier>ISSN: 1535-3893</identifier><identifier>EISSN: 1535-3907</identifier><identifier>DOI: 10.1021/pr3008732</identifier><identifier>PMID: 23082778</identifier><language>eng</language><publisher>United States: American Chemical Society</publisher><subject>Adult ; Aged ; Aged, 80 and over ; Amino Acid Sequence ; Antigens, Neoplasm - urine ; Area Under Curve ; Biomarkers, Tumor - urine ; Case-Control Studies ; Cell Adhesion Molecules - urine ; Chromatography, Liquid - methods ; Enzyme-Linked Immunosorbent Assay ; Exosomes - chemistry ; Female ; Hematuria - diagnosis ; Hernia - diagnosis ; Humans ; Isotope Labeling ; Male ; Mass Spectrometry - methods ; Middle Aged ; Molecular Sequence Data ; Neoplasm Proteins - urine ; Proteome - analysis ; Proteomics - methods ; Reproducibility of Results ; Urinary Bladder Neoplasms - chemistry ; Urinary Bladder Neoplasms - diagnosis</subject><ispartof>Journal of proteome research, 2012-12, Vol.11 (12), p.5611-5629</ispartof><rights>Copyright © 2012 American Chemical Society</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-a315t-9ef37b8aa55ba816fbcd10899bb9899983163586a07c222c85d66e870d7fd64f3</citedby><cites>FETCH-LOGICAL-a315t-9ef37b8aa55ba816fbcd10899bb9899983163586a07c222c85d66e870d7fd64f3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://pubs.acs.org/doi/pdf/10.1021/pr3008732$$EPDF$$P50$$Gacs$$H</linktopdf><linktohtml>$$Uhttps://pubs.acs.org/doi/10.1021/pr3008732$$EHTML$$P50$$Gacs$$H</linktohtml><link.rule.ids>314,780,784,2765,27076,27924,27925,56738,56788</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/23082778$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Chen, Chien-Lun</creatorcontrib><creatorcontrib>Lai, Yue-Fan</creatorcontrib><creatorcontrib>Tang, Petrus</creatorcontrib><creatorcontrib>Chien, Kun-Yi</creatorcontrib><creatorcontrib>Yu, Jau-Song</creatorcontrib><creatorcontrib>Tsai, Cheng-Han</creatorcontrib><creatorcontrib>Chen, Hsiao-Wei</creatorcontrib><creatorcontrib>Wu, Chih-Ching</creatorcontrib><creatorcontrib>Chung, Ting</creatorcontrib><creatorcontrib>Hsu, Chia-Wei</creatorcontrib><creatorcontrib>Chen, Chi-De</creatorcontrib><creatorcontrib>Chang, Yu-Sun</creatorcontrib><creatorcontrib>Chang, Phei-Lang</creatorcontrib><creatorcontrib>Chen, Yi-Ting</creatorcontrib><title>Comparative and Targeted Proteomic Analyses of Urinary Microparticles from Bladder Cancer and Hernia Patients</title><title>Journal of proteome research</title><addtitle>J. Proteome Res</addtitle><description>Bladder cancer is a common urologic cancer whose incidence continues to rise annually. Urinary microparticles are an attractive material for noninvasive bladder cancer biomarker discovery. In this study, we applied isotopic dimethylation labeling coupled with liquid chromatography-tandem mass spectrometry (LC–MS/MS) to discover bladder cancer biomarkers in urinary microparticles isolated from hernia (control) and bladder cancer patients. This approach identified 2964 proteins based on more than two distinct peptides, of which 2058 had not previously been reported as constituents of human urine exosomes/microparticles. A total of 107 differentially expressed proteins were identified as candidate biomarkers. Differences in the concentrations of 29 proteins (41 signature peptides) were precisely quantified by LC–MRM/MS in 48 urine samples of bladder cancer, hernia, and urinary tract infection/hematuria. Concentrations of 24 proteins changed significantly (p < 0.05) between bladder cancer (n = 28) and hernia (n = 12), with area-under-the-curve values ranging from 0.702 to 0.896. Finally, we quantified tumor-associated calcium-signal transducer 2 (TACSTD2) in raw urine specimens (n = 221) using a commercial ELISA and confirmed its potential value for diagnosis of bladder cancer. Our study reveals a strong association of TACSTD2 with bladder cancer and highlights the potential of human urinary microparticles in the noninvasive diagnosis of bladder cancer.</description><subject>Adult</subject><subject>Aged</subject><subject>Aged, 80 and over</subject><subject>Amino Acid Sequence</subject><subject>Antigens, Neoplasm - urine</subject><subject>Area Under Curve</subject><subject>Biomarkers, Tumor - urine</subject><subject>Case-Control Studies</subject><subject>Cell Adhesion Molecules - urine</subject><subject>Chromatography, Liquid - methods</subject><subject>Enzyme-Linked Immunosorbent Assay</subject><subject>Exosomes - chemistry</subject><subject>Female</subject><subject>Hematuria - diagnosis</subject><subject>Hernia - diagnosis</subject><subject>Humans</subject><subject>Isotope Labeling</subject><subject>Male</subject><subject>Mass Spectrometry - methods</subject><subject>Middle Aged</subject><subject>Molecular Sequence Data</subject><subject>Neoplasm Proteins - urine</subject><subject>Proteome - analysis</subject><subject>Proteomics - methods</subject><subject>Reproducibility of Results</subject><subject>Urinary Bladder Neoplasms - chemistry</subject><subject>Urinary Bladder Neoplasms - diagnosis</subject><issn>1535-3893</issn><issn>1535-3907</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2012</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNptkE1LwzAYgIMobk4P_gHJRdDDNB-mSY9a1AkTd9jO5W2SSkfb1KQV9u_N2MfJS95AnjzwPghdU_JACaOPneeEKMnZCRpTwcWUp0SeHu4q5SN0EcKaECok4edoxDhRTEo1Rk3mmg489NWvxdAavAT_bXtr8MK73rqm0vi5hXoTbMCuxCtfteA3-LPS3sWPfaXr-FJ61-CXGoyxHmfQ6ji2tpn1bQV4Ef227cMlOiuhDvZqPydo9fa6zGbT-df7R_Y8nwKnop-mtuSyUABCFKBoUhbaUKLStCjSeKaK04QLlQCRmjGmlTBJYpUkRpYmeSr5BN3tvJ13P4MNfd5UQdu6hta6IeSUcSkooTHQBN3v0LhPCN6WeeerJq6YU5Jv6-bHupG92WuHorHmSB5yRuB2B4AO-doNPpYL_4j-ALdHgMg</recordid><startdate>20121207</startdate><enddate>20121207</enddate><creator>Chen, Chien-Lun</creator><creator>Lai, Yue-Fan</creator><creator>Tang, Petrus</creator><creator>Chien, Kun-Yi</creator><creator>Yu, Jau-Song</creator><creator>Tsai, Cheng-Han</creator><creator>Chen, Hsiao-Wei</creator><creator>Wu, Chih-Ching</creator><creator>Chung, Ting</creator><creator>Hsu, Chia-Wei</creator><creator>Chen, Chi-De</creator><creator>Chang, Yu-Sun</creator><creator>Chang, Phei-Lang</creator><creator>Chen, Yi-Ting</creator><general>American Chemical Society</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>20121207</creationdate><title>Comparative and Targeted Proteomic Analyses of Urinary Microparticles from Bladder Cancer and Hernia Patients</title><author>Chen, Chien-Lun ; Lai, Yue-Fan ; Tang, Petrus ; Chien, Kun-Yi ; Yu, Jau-Song ; Tsai, Cheng-Han ; Chen, Hsiao-Wei ; Wu, Chih-Ching ; Chung, Ting ; Hsu, Chia-Wei ; Chen, Chi-De ; Chang, Yu-Sun ; Chang, Phei-Lang ; Chen, Yi-Ting</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-a315t-9ef37b8aa55ba816fbcd10899bb9899983163586a07c222c85d66e870d7fd64f3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2012</creationdate><topic>Adult</topic><topic>Aged</topic><topic>Aged, 80 and over</topic><topic>Amino Acid Sequence</topic><topic>Antigens, Neoplasm - urine</topic><topic>Area Under Curve</topic><topic>Biomarkers, Tumor - urine</topic><topic>Case-Control Studies</topic><topic>Cell Adhesion Molecules - urine</topic><topic>Chromatography, Liquid - methods</topic><topic>Enzyme-Linked Immunosorbent Assay</topic><topic>Exosomes - chemistry</topic><topic>Female</topic><topic>Hematuria - diagnosis</topic><topic>Hernia - diagnosis</topic><topic>Humans</topic><topic>Isotope Labeling</topic><topic>Male</topic><topic>Mass Spectrometry - methods</topic><topic>Middle Aged</topic><topic>Molecular Sequence Data</topic><topic>Neoplasm Proteins - urine</topic><topic>Proteome - analysis</topic><topic>Proteomics - methods</topic><topic>Reproducibility of Results</topic><topic>Urinary Bladder Neoplasms - chemistry</topic><topic>Urinary Bladder Neoplasms - diagnosis</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Chen, Chien-Lun</creatorcontrib><creatorcontrib>Lai, Yue-Fan</creatorcontrib><creatorcontrib>Tang, Petrus</creatorcontrib><creatorcontrib>Chien, Kun-Yi</creatorcontrib><creatorcontrib>Yu, Jau-Song</creatorcontrib><creatorcontrib>Tsai, Cheng-Han</creatorcontrib><creatorcontrib>Chen, Hsiao-Wei</creatorcontrib><creatorcontrib>Wu, Chih-Ching</creatorcontrib><creatorcontrib>Chung, Ting</creatorcontrib><creatorcontrib>Hsu, Chia-Wei</creatorcontrib><creatorcontrib>Chen, Chi-De</creatorcontrib><creatorcontrib>Chang, Yu-Sun</creatorcontrib><creatorcontrib>Chang, Phei-Lang</creatorcontrib><creatorcontrib>Chen, Yi-Ting</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>Journal of proteome research</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Chen, Chien-Lun</au><au>Lai, Yue-Fan</au><au>Tang, Petrus</au><au>Chien, Kun-Yi</au><au>Yu, Jau-Song</au><au>Tsai, Cheng-Han</au><au>Chen, Hsiao-Wei</au><au>Wu, Chih-Ching</au><au>Chung, Ting</au><au>Hsu, Chia-Wei</au><au>Chen, Chi-De</au><au>Chang, Yu-Sun</au><au>Chang, Phei-Lang</au><au>Chen, Yi-Ting</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Comparative and Targeted Proteomic Analyses of Urinary Microparticles from Bladder Cancer and Hernia Patients</atitle><jtitle>Journal of proteome research</jtitle><addtitle>J. Proteome Res</addtitle><date>2012-12-07</date><risdate>2012</risdate><volume>11</volume><issue>12</issue><spage>5611</spage><epage>5629</epage><pages>5611-5629</pages><issn>1535-3893</issn><eissn>1535-3907</eissn><abstract>Bladder cancer is a common urologic cancer whose incidence continues to rise annually. Urinary microparticles are an attractive material for noninvasive bladder cancer biomarker discovery. In this study, we applied isotopic dimethylation labeling coupled with liquid chromatography-tandem mass spectrometry (LC–MS/MS) to discover bladder cancer biomarkers in urinary microparticles isolated from hernia (control) and bladder cancer patients. This approach identified 2964 proteins based on more than two distinct peptides, of which 2058 had not previously been reported as constituents of human urine exosomes/microparticles. A total of 107 differentially expressed proteins were identified as candidate biomarkers. Differences in the concentrations of 29 proteins (41 signature peptides) were precisely quantified by LC–MRM/MS in 48 urine samples of bladder cancer, hernia, and urinary tract infection/hematuria. Concentrations of 24 proteins changed significantly (p < 0.05) between bladder cancer (n = 28) and hernia (n = 12), with area-under-the-curve values ranging from 0.702 to 0.896. Finally, we quantified tumor-associated calcium-signal transducer 2 (TACSTD2) in raw urine specimens (n = 221) using a commercial ELISA and confirmed its potential value for diagnosis of bladder cancer. Our study reveals a strong association of TACSTD2 with bladder cancer and highlights the potential of human urinary microparticles in the noninvasive diagnosis of bladder cancer.</abstract><cop>United States</cop><pub>American Chemical Society</pub><pmid>23082778</pmid><doi>10.1021/pr3008732</doi><tpages>19</tpages></addata></record> |
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| ispartof | Journal of proteome research, 2012-12, Vol.11 (12), p.5611-5629 |
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| subjects | Adult Aged Aged, 80 and over Amino Acid Sequence Antigens, Neoplasm - urine Area Under Curve Biomarkers, Tumor - urine Case-Control Studies Cell Adhesion Molecules - urine Chromatography, Liquid - methods Enzyme-Linked Immunosorbent Assay Exosomes - chemistry Female Hematuria - diagnosis Hernia - diagnosis Humans Isotope Labeling Male Mass Spectrometry - methods Middle Aged Molecular Sequence Data Neoplasm Proteins - urine Proteome - analysis Proteomics - methods Reproducibility of Results Urinary Bladder Neoplasms - chemistry Urinary Bladder Neoplasms - diagnosis |
| title | Comparative and Targeted Proteomic Analyses of Urinary Microparticles from Bladder Cancer and Hernia Patients |
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