Prognostic Implication of Urothelial Stem Cell Markers Differs According to Primary Tumour Location in Non-Muscle-Invasive Bladder Cancer
Background/Aims: This study aimed to validate the value of urothelial stem cell (USC) markers ΔNp63, integrin β4, CD47, and CD44v6 in predicting the prognosis of non-muscle invasive bladder cancer (NMIBC) located in different anatomic regions of bladder. Methods: The study reviewed the clinicopathol...
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| Veröffentlicht in: | Cellular Physiology and Biochemistry 2018-08, Vol.48 (6), p.2364-2373 |
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| creator | Wang, Longwang Zhao, Jun Yang, Chenlu Kuang, Renrui Kazobinka, Gallina Pang, Zili Hou, Teng |
| description | Background/Aims: This study aimed to validate the value of urothelial stem cell (USC) markers ΔNp63, integrin β4, CD47, and CD44v6 in predicting the prognosis of non-muscle invasive bladder cancer (NMIBC) located in different anatomic regions of bladder. Methods: The study reviewed the clinicopathologic data of 169 patients with NMIBC. Using real-time PCR and immunohistochemistry, the expression of ΔNp63, integrin β4, CD47, and CD44v6 in archived specimens of patients with NMIBC were validated. Kaplan–Meier analysis and Cox proportional hazards model were used to assess the prognostic impact of USC markers for recurrent-free survival (RFS). Results: The Real-time PCR data showed that the expression of USC markers were higher in tumors located in the trigone and posterior wall than that in other regions of bladder (P< 0.05). Statistical analysis showed that high expression of ΔNp63 was correlated with tumor stage (P=0.023) and tumor size (P=0.001), that high expression of integrin β4 was correlated with tumor stage (P=0.026), tumor grade (P=0.005) and tumor size (P=0.003), and that high integrin β4, CD47, and CD44v6 expression were significantly associated with tumor recurrence (P=0.032, P=0.010, and P=0.043, respectively). Moreover, high expression of ΔNp63 and integrin β4 was correlated with poor RFS in patients with tumors located in the trigone (P=0.025 and P=0.023, respectively). High expression of integrin β4, CD47, and CD44v6 was correlated with poor RFS in patients with tumors in the posterior wall (P=0.017, P=0.033 and P=0.047, respectively). High expression of integrin β4 and CD47 was correlated with poor RFS in patients with tumors in the trigone/posterior wall area (P=0.002 and P=0.005, respectively). Conclusion: Our results suggest that USC markers are linked with poor prognosis of NMIBC patients, especially in patients with tumors in the trigone and posterior wall. |
| doi_str_mv | 10.1159/000492652 |
| format | Article |
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Methods: The study reviewed the clinicopathologic data of 169 patients with NMIBC. Using real-time PCR and immunohistochemistry, the expression of ΔNp63, integrin β4, CD47, and CD44v6 in archived specimens of patients with NMIBC were validated. Kaplan–Meier analysis and Cox proportional hazards model were used to assess the prognostic impact of USC markers for recurrent-free survival (RFS). Results: The Real-time PCR data showed that the expression of USC markers were higher in tumors located in the trigone and posterior wall than that in other regions of bladder (P< 0.05). Statistical analysis showed that high expression of ΔNp63 was correlated with tumor stage (P=0.023) and tumor size (P=0.001), that high expression of integrin β4 was correlated with tumor stage (P=0.026), tumor grade (P=0.005) and tumor size (P=0.003), and that high integrin β4, CD47, and CD44v6 expression were significantly associated with tumor recurrence (P=0.032, P=0.010, and P=0.043, respectively). Moreover, high expression of ΔNp63 and integrin β4 was correlated with poor RFS in patients with tumors located in the trigone (P=0.025 and P=0.023, respectively). High expression of integrin β4, CD47, and CD44v6 was correlated with poor RFS in patients with tumors in the posterior wall (P=0.017, P=0.033 and P=0.047, respectively). High expression of integrin β4 and CD47 was correlated with poor RFS in patients with tumors in the trigone/posterior wall area (P=0.002 and P=0.005, respectively). Conclusion: Our results suggest that USC markers are linked with poor prognosis of NMIBC patients, especially in patients with tumors in the trigone and posterior wall.</description><identifier>ISSN: 1015-8987</identifier><identifier>EISSN: 1421-9778</identifier><identifier>DOI: 10.1159/000492652</identifier><identifier>PMID: 30114689</identifier><language>eng</language><publisher>Basel, Switzerland: S. Karger AG</publisher><subject>Biomarkers ; Biomarkers, Tumor - genetics ; Biomarkers, Tumor - metabolism ; Bladder cancer ; Breast cancer ; Cancer therapies ; CD47 Antigen - genetics ; CD47 Antigen - metabolism ; Chemotherapy ; Disease-Free Survival ; Female ; Health aspects ; Humans ; Hyaluronan Receptors - genetics ; Hyaluronan Receptors - metabolism ; Immunohistochemistry ; Integrin beta4 - genetics ; Integrin beta4 - metabolism ; Kaplan-Meier Estimate ; Male ; Medical prognosis ; Middle Aged ; Morphology ; Neoplasm Staging ; NMIBC ; Original Paper ; Physiological aspects ; Posterior wall ; Prognosis ; Proportional Hazards Models ; RFS ; Stem cell marker ; Stem cells ; Transcription Factors - genetics ; Transcription Factors - metabolism ; Trigone ; Tumor Suppressor Proteins - genetics ; Tumor Suppressor Proteins - metabolism ; Tumorigenesis ; Urinary Bladder Neoplasms - metabolism ; Urinary Bladder Neoplasms - mortality ; Urinary Bladder Neoplasms - pathology</subject><ispartof>Cellular Physiology and Biochemistry, 2018-08, Vol.48 (6), p.2364-2373</ispartof><rights>2018 The Author(s). Published by S. Karger AG, Basel</rights><rights>2018 The Author(s). Published by S. Karger AG, Basel.</rights><rights>COPYRIGHT 2018 S. Karger AG</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c502t-aabf8bb106c21c24f4f542d5a092a08d9a8a28f1674577cc31eda808b09d7ea33</citedby></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,777,781,861,2096,27616,27905,27906</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/30114689$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Wang, Longwang</creatorcontrib><creatorcontrib>Zhao, Jun</creatorcontrib><creatorcontrib>Yang, Chenlu</creatorcontrib><creatorcontrib>Kuang, Renrui</creatorcontrib><creatorcontrib>Kazobinka, Gallina</creatorcontrib><creatorcontrib>Pang, Zili</creatorcontrib><creatorcontrib>Hou, Teng</creatorcontrib><title>Prognostic Implication of Urothelial Stem Cell Markers Differs According to Primary Tumour Location in Non-Muscle-Invasive Bladder Cancer</title><title>Cellular Physiology and Biochemistry</title><addtitle>Cell Physiol Biochem</addtitle><description>Background/Aims: This study aimed to validate the value of urothelial stem cell (USC) markers ΔNp63, integrin β4, CD47, and CD44v6 in predicting the prognosis of non-muscle invasive bladder cancer (NMIBC) located in different anatomic regions of bladder. Methods: The study reviewed the clinicopathologic data of 169 patients with NMIBC. Using real-time PCR and immunohistochemistry, the expression of ΔNp63, integrin β4, CD47, and CD44v6 in archived specimens of patients with NMIBC were validated. Kaplan–Meier analysis and Cox proportional hazards model were used to assess the prognostic impact of USC markers for recurrent-free survival (RFS). Results: The Real-time PCR data showed that the expression of USC markers were higher in tumors located in the trigone and posterior wall than that in other regions of bladder (P< 0.05). Statistical analysis showed that high expression of ΔNp63 was correlated with tumor stage (P=0.023) and tumor size (P=0.001), that high expression of integrin β4 was correlated with tumor stage (P=0.026), tumor grade (P=0.005) and tumor size (P=0.003), and that high integrin β4, CD47, and CD44v6 expression were significantly associated with tumor recurrence (P=0.032, P=0.010, and P=0.043, respectively). Moreover, high expression of ΔNp63 and integrin β4 was correlated with poor RFS in patients with tumors located in the trigone (P=0.025 and P=0.023, respectively). High expression of integrin β4, CD47, and CD44v6 was correlated with poor RFS in patients with tumors in the posterior wall (P=0.017, P=0.033 and P=0.047, respectively). High expression of integrin β4 and CD47 was correlated with poor RFS in patients with tumors in the trigone/posterior wall area (P=0.002 and P=0.005, respectively). Conclusion: Our results suggest that USC markers are linked with poor prognosis of NMIBC patients, especially in patients with tumors in the trigone and posterior wall.</description><subject>Biomarkers</subject><subject>Biomarkers, Tumor - genetics</subject><subject>Biomarkers, Tumor - metabolism</subject><subject>Bladder cancer</subject><subject>Breast cancer</subject><subject>Cancer therapies</subject><subject>CD47 Antigen - genetics</subject><subject>CD47 Antigen - metabolism</subject><subject>Chemotherapy</subject><subject>Disease-Free Survival</subject><subject>Female</subject><subject>Health aspects</subject><subject>Humans</subject><subject>Hyaluronan Receptors - genetics</subject><subject>Hyaluronan Receptors - metabolism</subject><subject>Immunohistochemistry</subject><subject>Integrin beta4 - genetics</subject><subject>Integrin beta4 - metabolism</subject><subject>Kaplan-Meier Estimate</subject><subject>Male</subject><subject>Medical prognosis</subject><subject>Middle Aged</subject><subject>Morphology</subject><subject>Neoplasm Staging</subject><subject>NMIBC</subject><subject>Original Paper</subject><subject>Physiological aspects</subject><subject>Posterior wall</subject><subject>Prognosis</subject><subject>Proportional Hazards Models</subject><subject>RFS</subject><subject>Stem cell marker</subject><subject>Stem cells</subject><subject>Transcription Factors - genetics</subject><subject>Transcription Factors - metabolism</subject><subject>Trigone</subject><subject>Tumor Suppressor Proteins - genetics</subject><subject>Tumor Suppressor Proteins - metabolism</subject><subject>Tumorigenesis</subject><subject>Urinary Bladder Neoplasms - metabolism</subject><subject>Urinary Bladder Neoplasms - mortality</subject><subject>Urinary Bladder Neoplasms - pathology</subject><issn>1015-8987</issn><issn>1421-9778</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2018</creationdate><recordtype>article</recordtype><sourceid>M--</sourceid><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DOA</sourceid><recordid>eNpdkk1v1DAQhiMEoh9w4I6QJS5wSLGdOLaPy_K10hYq0Z6jiT-Ct4m9tZNK_Qn8a1yy7AH5MLb1zDszr6YoXhF8QQiTHzDGtaQNo0-KU1JTUkrOxdN8x4SVQgp-UpyltMP5ySV9XpxUmJC6EfK0-H0VQ-9DmpxCm3E_OAWTCx4Fi25imH6ZwcGAfk5mRGszDOgS4q2JCX1y1j7GlVIhaud7NAV0Fd0I8QFdz2OYI9qGg5jz6Hvw5eWc1GDKjb-H5O4N-jiA1iaiNXhl4ovimYUhmZeHeF7cfPl8vf5Wbn983axX21IxTKcSoLOi6whuFCWK1ra2rKaaAZYUsNASBFBhScNrxrlSFTEaBBYdlpobqKrzYrPo6gC7dr-03AZw7d-PEPsWYrZjMK0mnJJGdYJ3pqaYSiYYbXCnFOFKqi5rvVu09jHczSZN7eiSyj6BN2FOLcXZfcZFQzP69j90lz3yedKWklwHE05Ypi4Wqodc33kbpggqH21Gp4I31uX_VVNxRqVsSE54vySoGFKKxh4nIrh9XI72uByZfXNoYe5Go4_kv23IwOsFuIXYm3gEDvl_AHC0vHg</recordid><startdate>20180801</startdate><enddate>20180801</enddate><creator>Wang, Longwang</creator><creator>Zhao, Jun</creator><creator>Yang, Chenlu</creator><creator>Kuang, Renrui</creator><creator>Kazobinka, Gallina</creator><creator>Pang, Zili</creator><creator>Hou, Teng</creator><general>S. Karger AG</general><general>Cell Physiol Biochem Press GmbH & Co KG</general><scope>M--</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>IAO</scope><scope>3V.</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>BENPR</scope><scope>CCPQU</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>K9.</scope><scope>M0S</scope><scope>M1P</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>7X8</scope><scope>DOA</scope></search><sort><creationdate>20180801</creationdate><title>Prognostic Implication of Urothelial Stem Cell Markers Differs According to Primary Tumour Location in Non-Muscle-Invasive Bladder Cancer</title><author>Wang, Longwang ; Zhao, Jun ; Yang, Chenlu ; Kuang, Renrui ; Kazobinka, Gallina ; Pang, Zili ; Hou, Teng</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c502t-aabf8bb106c21c24f4f542d5a092a08d9a8a28f1674577cc31eda808b09d7ea33</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2018</creationdate><topic>Biomarkers</topic><topic>Biomarkers, Tumor - genetics</topic><topic>Biomarkers, Tumor - metabolism</topic><topic>Bladder cancer</topic><topic>Breast cancer</topic><topic>Cancer therapies</topic><topic>CD47 Antigen - genetics</topic><topic>CD47 Antigen - metabolism</topic><topic>Chemotherapy</topic><topic>Disease-Free Survival</topic><topic>Female</topic><topic>Health aspects</topic><topic>Humans</topic><topic>Hyaluronan Receptors - genetics</topic><topic>Hyaluronan Receptors - metabolism</topic><topic>Immunohistochemistry</topic><topic>Integrin beta4 - genetics</topic><topic>Integrin beta4 - metabolism</topic><topic>Kaplan-Meier Estimate</topic><topic>Male</topic><topic>Medical prognosis</topic><topic>Middle Aged</topic><topic>Morphology</topic><topic>Neoplasm Staging</topic><topic>NMIBC</topic><topic>Original Paper</topic><topic>Physiological aspects</topic><topic>Posterior wall</topic><topic>Prognosis</topic><topic>Proportional Hazards Models</topic><topic>RFS</topic><topic>Stem cell marker</topic><topic>Stem cells</topic><topic>Transcription Factors - genetics</topic><topic>Transcription Factors - metabolism</topic><topic>Trigone</topic><topic>Tumor Suppressor Proteins - genetics</topic><topic>Tumor Suppressor Proteins - metabolism</topic><topic>Tumorigenesis</topic><topic>Urinary Bladder Neoplasms - metabolism</topic><topic>Urinary Bladder Neoplasms - mortality</topic><topic>Urinary Bladder Neoplasms - pathology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Wang, Longwang</creatorcontrib><creatorcontrib>Zhao, Jun</creatorcontrib><creatorcontrib>Yang, Chenlu</creatorcontrib><creatorcontrib>Kuang, Renrui</creatorcontrib><creatorcontrib>Kazobinka, Gallina</creatorcontrib><creatorcontrib>Pang, Zili</creatorcontrib><creatorcontrib>Hou, Teng</creatorcontrib><collection>Karger Open Access</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Gale Academic OneFile</collection><collection>ProQuest Central (Corporate)</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</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>ProQuest Central</collection><collection>ProQuest One Community College</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical 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>DOAJ Directory of Open Access Journals</collection><jtitle>Cellular Physiology and Biochemistry</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Wang, Longwang</au><au>Zhao, Jun</au><au>Yang, Chenlu</au><au>Kuang, Renrui</au><au>Kazobinka, Gallina</au><au>Pang, Zili</au><au>Hou, Teng</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Prognostic Implication of Urothelial Stem Cell Markers Differs According to Primary Tumour Location in Non-Muscle-Invasive Bladder Cancer</atitle><jtitle>Cellular Physiology and Biochemistry</jtitle><addtitle>Cell Physiol Biochem</addtitle><date>2018-08-01</date><risdate>2018</risdate><volume>48</volume><issue>6</issue><spage>2364</spage><epage>2373</epage><pages>2364-2373</pages><issn>1015-8987</issn><eissn>1421-9778</eissn><abstract>Background/Aims: This study aimed to validate the value of urothelial stem cell (USC) markers ΔNp63, integrin β4, CD47, and CD44v6 in predicting the prognosis of non-muscle invasive bladder cancer (NMIBC) located in different anatomic regions of bladder. Methods: The study reviewed the clinicopathologic data of 169 patients with NMIBC. Using real-time PCR and immunohistochemistry, the expression of ΔNp63, integrin β4, CD47, and CD44v6 in archived specimens of patients with NMIBC were validated. Kaplan–Meier analysis and Cox proportional hazards model were used to assess the prognostic impact of USC markers for recurrent-free survival (RFS). Results: The Real-time PCR data showed that the expression of USC markers were higher in tumors located in the trigone and posterior wall than that in other regions of bladder (P< 0.05). Statistical analysis showed that high expression of ΔNp63 was correlated with tumor stage (P=0.023) and tumor size (P=0.001), that high expression of integrin β4 was correlated with tumor stage (P=0.026), tumor grade (P=0.005) and tumor size (P=0.003), and that high integrin β4, CD47, and CD44v6 expression were significantly associated with tumor recurrence (P=0.032, P=0.010, and P=0.043, respectively). Moreover, high expression of ΔNp63 and integrin β4 was correlated with poor RFS in patients with tumors located in the trigone (P=0.025 and P=0.023, respectively). High expression of integrin β4, CD47, and CD44v6 was correlated with poor RFS in patients with tumors in the posterior wall (P=0.017, P=0.033 and P=0.047, respectively). High expression of integrin β4 and CD47 was correlated with poor RFS in patients with tumors in the trigone/posterior wall area (P=0.002 and P=0.005, respectively). Conclusion: Our results suggest that USC markers are linked with poor prognosis of NMIBC patients, especially in patients with tumors in the trigone and posterior wall.</abstract><cop>Basel, Switzerland</cop><pub>S. Karger AG</pub><pmid>30114689</pmid><doi>10.1159/000492652</doi><tpages>10</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Biomarkers Biomarkers, Tumor - genetics Biomarkers, Tumor - metabolism Bladder cancer Breast cancer Cancer therapies CD47 Antigen - genetics CD47 Antigen - metabolism Chemotherapy Disease-Free Survival Female Health aspects Humans Hyaluronan Receptors - genetics Hyaluronan Receptors - metabolism Immunohistochemistry Integrin beta4 - genetics Integrin beta4 - metabolism Kaplan-Meier Estimate Male Medical prognosis Middle Aged Morphology Neoplasm Staging NMIBC Original Paper Physiological aspects Posterior wall Prognosis Proportional Hazards Models RFS Stem cell marker Stem cells Transcription Factors - genetics Transcription Factors - metabolism Trigone Tumor Suppressor Proteins - genetics Tumor Suppressor Proteins - metabolism Tumorigenesis Urinary Bladder Neoplasms - metabolism Urinary Bladder Neoplasms - mortality Urinary Bladder Neoplasms - pathology |
| title | Prognostic Implication of Urothelial Stem Cell Markers Differs According to Primary Tumour Location in Non-Muscle-Invasive Bladder Cancer |
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