Impact of Clinicopathological Characteristics and Tissue Inhibitor of Metalloproteinase-3 Polymorphism Rs9619311 on Biochemical Recurrence in Taiwanese Patients with Prostate Cancer
The tissue inhibitors of metalloproteinases-3 (TIMP3) are not only endogenous regulators of matrix metalloproteinases (MMPs), but also induce apoptosis and inhibit endothelial cell migration and angiogenesis. The focus of this study was to investigate the relationship between TIMP3 genetic polymorph...
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| Veröffentlicht in: | International journal of environmental research and public health 2022-12, Vol.20 (1), p.306 |
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| creator | Hsieh, Chun-Yu Lin, Chia-Yen Wang, Shian-Shiang Chou, Ying-Erh Chien, Ming-Hsien Wen, Yu-Ching Hsieh, Ming-Ju Yang, Shun-Fa |
| description | The tissue inhibitors of metalloproteinases-3 (TIMP3) are not only endogenous regulators of matrix metalloproteinases (MMPs), but also induce apoptosis and inhibit endothelial cell migration and angiogenesis. The focus of this study was to investigate the relationship between TIMP3 genetic polymorphisms and biochemical recurrence and clinicopathological features of prostate cancer. The TIMP3 rs9619311, rs9862, and rs11547635 genetic polymorphisms were analyzed by real-time polymerase chain reaction to determine their genotypic distributions in 579 patients with prostate cancer. This study found that individuals with the TIMP3 rs9619311 TC or TC + CC genotypes have a significantly higher risk of biochemical recurrence of prostate cancer (
= 0.036 and 0.033, respectively). Moreover, in the multivariate analysis, our results showed that pathologic Gleason grade, pathologic T stage, seminal vesicle invasion, lymphovascular invasion, and TIMP3 rs9619311 were associated with increased odds of biochemical recurrence. Patients with a PSA concentration under 7 ng/mL that were found to have the TIMP3 rs9619311 genetic polymorphism were associated with Gleason total score upgrade (
= 0.012) and grade group upgrade (
= 0.023). Compared with the CC homozygous, the TIMP3 rs9862 CT + TT polymorphic variant was found to be associated with clinically advanced tumor stage (
= 0.030) and Gleason total score upgrade (
= 0.002) in prostate cancer patients. In conclusion, the results of our study demonstrated that the TIMP3 rs9619311 genetic polymorphism was significantly associated with susceptibility to biochemical recurrence of prostate cancer. TIMP3 genetic polymorphisms, especially rs9619311, can serve as key predictors of biochemical recurrence and disease prognosis of prostate cancer. |
| doi_str_mv | 10.3390/ijerph20010306 |
| format | Article |
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= 0.036 and 0.033, respectively). Moreover, in the multivariate analysis, our results showed that pathologic Gleason grade, pathologic T stage, seminal vesicle invasion, lymphovascular invasion, and TIMP3 rs9619311 were associated with increased odds of biochemical recurrence. Patients with a PSA concentration under 7 ng/mL that were found to have the TIMP3 rs9619311 genetic polymorphism were associated with Gleason total score upgrade (
= 0.012) and grade group upgrade (
= 0.023). Compared with the CC homozygous, the TIMP3 rs9862 CT + TT polymorphic variant was found to be associated with clinically advanced tumor stage (
= 0.030) and Gleason total score upgrade (
= 0.002) in prostate cancer patients. In conclusion, the results of our study demonstrated that the TIMP3 rs9619311 genetic polymorphism was significantly associated with susceptibility to biochemical recurrence of prostate cancer. TIMP3 genetic polymorphisms, especially rs9619311, can serve as key predictors of biochemical recurrence and disease prognosis of prostate cancer.</description><identifier>ISSN: 1660-4601</identifier><identifier>ISSN: 1661-7827</identifier><identifier>EISSN: 1660-4601</identifier><identifier>DOI: 10.3390/ijerph20010306</identifier><identifier>PMID: 36612628</identifier><language>eng</language><publisher>Switzerland: MDPI AG</publisher><subject>Age ; Angiogenesis ; Apoptosis ; Asian people ; Biochemistry ; Cervical cancer ; Endothelial cells ; Extracellular matrix ; Gene expression ; Gene polymorphism ; Genotype ; Genotypes ; Humans ; Liver cancer ; Male ; Matrix metalloproteinase ; Matrix metalloproteinases ; Medical prognosis ; Metalloproteases - genetics ; Metalloproteinase ; Multivariate analysis ; Polymerase chain reaction ; Polymorphism ; Polymorphism, Genetic ; Prostate cancer ; Prostate-Specific Antigen ; Prostatic Neoplasms - genetics ; Prostatic Neoplasms - pathology ; Seminal vesicle ; Software ; Tissue inhibitor of metalloproteinase 3 ; Tissue Inhibitor of Metalloproteinase-3 - genetics ; Tumors</subject><ispartof>International journal of environmental research and public health, 2022-12, Vol.20 (1), p.306</ispartof><rights>2022 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2022 by the authors. 2022</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><cites>FETCH-LOGICAL-c373t-a669590e6544841429e627b494337e388551dcdc9dd3c4921e745b0694bb8c5a3</cites><orcidid>0000-0002-0084-7231 ; 0000-0002-6303-2187 ; 0000-0003-3032-0198 ; 0000-0001-9726-3234 ; 0000-0002-0365-7927</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC9819570/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC9819570/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,881,27901,27902,53766,53768</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/36612628$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Hsieh, Chun-Yu</creatorcontrib><creatorcontrib>Lin, Chia-Yen</creatorcontrib><creatorcontrib>Wang, Shian-Shiang</creatorcontrib><creatorcontrib>Chou, Ying-Erh</creatorcontrib><creatorcontrib>Chien, Ming-Hsien</creatorcontrib><creatorcontrib>Wen, Yu-Ching</creatorcontrib><creatorcontrib>Hsieh, Ming-Ju</creatorcontrib><creatorcontrib>Yang, Shun-Fa</creatorcontrib><title>Impact of Clinicopathological Characteristics and Tissue Inhibitor of Metalloproteinase-3 Polymorphism Rs9619311 on Biochemical Recurrence in Taiwanese Patients with Prostate Cancer</title><title>International journal of environmental research and public health</title><addtitle>Int J Environ Res Public Health</addtitle><description>The tissue inhibitors of metalloproteinases-3 (TIMP3) are not only endogenous regulators of matrix metalloproteinases (MMPs), but also induce apoptosis and inhibit endothelial cell migration and angiogenesis. The focus of this study was to investigate the relationship between TIMP3 genetic polymorphisms and biochemical recurrence and clinicopathological features of prostate cancer. The TIMP3 rs9619311, rs9862, and rs11547635 genetic polymorphisms were analyzed by real-time polymerase chain reaction to determine their genotypic distributions in 579 patients with prostate cancer. This study found that individuals with the TIMP3 rs9619311 TC or TC + CC genotypes have a significantly higher risk of biochemical recurrence of prostate cancer (
= 0.036 and 0.033, respectively). Moreover, in the multivariate analysis, our results showed that pathologic Gleason grade, pathologic T stage, seminal vesicle invasion, lymphovascular invasion, and TIMP3 rs9619311 were associated with increased odds of biochemical recurrence. Patients with a PSA concentration under 7 ng/mL that were found to have the TIMP3 rs9619311 genetic polymorphism were associated with Gleason total score upgrade (
= 0.012) and grade group upgrade (
= 0.023). Compared with the CC homozygous, the TIMP3 rs9862 CT + TT polymorphic variant was found to be associated with clinically advanced tumor stage (
= 0.030) and Gleason total score upgrade (
= 0.002) in prostate cancer patients. In conclusion, the results of our study demonstrated that the TIMP3 rs9619311 genetic polymorphism was significantly associated with susceptibility to biochemical recurrence of prostate cancer. TIMP3 genetic polymorphisms, especially rs9619311, can serve as key predictors of biochemical recurrence and disease prognosis of prostate cancer.</description><subject>Age</subject><subject>Angiogenesis</subject><subject>Apoptosis</subject><subject>Asian people</subject><subject>Biochemistry</subject><subject>Cervical cancer</subject><subject>Endothelial cells</subject><subject>Extracellular matrix</subject><subject>Gene expression</subject><subject>Gene polymorphism</subject><subject>Genotype</subject><subject>Genotypes</subject><subject>Humans</subject><subject>Liver cancer</subject><subject>Male</subject><subject>Matrix metalloproteinase</subject><subject>Matrix metalloproteinases</subject><subject>Medical prognosis</subject><subject>Metalloproteases - genetics</subject><subject>Metalloproteinase</subject><subject>Multivariate analysis</subject><subject>Polymerase chain reaction</subject><subject>Polymorphism</subject><subject>Polymorphism, Genetic</subject><subject>Prostate cancer</subject><subject>Prostate-Specific Antigen</subject><subject>Prostatic Neoplasms - genetics</subject><subject>Prostatic Neoplasms - pathology</subject><subject>Seminal vesicle</subject><subject>Software</subject><subject>Tissue inhibitor of metalloproteinase 3</subject><subject>Tissue Inhibitor of Metalloproteinase-3 - genetics</subject><subject>Tumors</subject><issn>1660-4601</issn><issn>1661-7827</issn><issn>1660-4601</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2022</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>BENPR</sourceid><recordid>eNpdkk9v1DAQxSMEon_gyhFZ4sIlxY4dJ74gwYrCSkWsquUcOc5sMyvHDrZD1Q_G98PblqrlZEvzmzfvjaYo3jB6xrmiH3APYR4rShnlVD4rjpmUtBSSsueP_kfFSYx7SnkrpHpZHHEpWSWr9rj4s55mbRLxO7Ky6ND4WafRW3-FRluyGnXIZQgYE5pItBvIFmNcgKzdiD0mHw693yFpa_0cfAJ0OkLJycbbm8lndxgnchmVZIozRrwjn9GbEabbCZdglhDAGSDoyFbjtXYQgWx0QnApkmtMI9kEH5NOQFY6k-FV8WKnbYTX9-9p8fP8y3b1rbz48XW9-nRRGt7wVGopVa0oyFqIVjBRKZBV0wslOG-At21ds8EMRg0DN0JVDBpR91Qq0fetqTU_LT7e6c5LP8FgsqGgbTcHnHS46bzG7mnF4dhd-d-dapmqG5oF3t8LBP9rgZi6CaMBa3NIv8SuavJWmsPojL77D937Jbgc75ZiraTtgTq7o0zeSAywezDDaHe4iO7pReSGt48jPOD_ToD_BQgDtZ4</recordid><startdate>20221225</startdate><enddate>20221225</enddate><creator>Hsieh, Chun-Yu</creator><creator>Lin, Chia-Yen</creator><creator>Wang, Shian-Shiang</creator><creator>Chou, Ying-Erh</creator><creator>Chien, Ming-Hsien</creator><creator>Wen, Yu-Ching</creator><creator>Hsieh, Ming-Ju</creator><creator>Yang, Shun-Fa</creator><general>MDPI AG</general><general>MDPI</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>3V.</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8C1</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BENPR</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>K9.</scope><scope>M0S</scope><scope>M1P</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>7X8</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0002-0084-7231</orcidid><orcidid>https://orcid.org/0000-0002-6303-2187</orcidid><orcidid>https://orcid.org/0000-0003-3032-0198</orcidid><orcidid>https://orcid.org/0000-0001-9726-3234</orcidid><orcidid>https://orcid.org/0000-0002-0365-7927</orcidid></search><sort><creationdate>20221225</creationdate><title>Impact of Clinicopathological Characteristics and Tissue Inhibitor of Metalloproteinase-3 Polymorphism Rs9619311 on Biochemical Recurrence in Taiwanese Patients with Prostate Cancer</title><author>Hsieh, Chun-Yu ; Lin, Chia-Yen ; Wang, Shian-Shiang ; Chou, Ying-Erh ; Chien, Ming-Hsien ; Wen, Yu-Ching ; Hsieh, Ming-Ju ; Yang, Shun-Fa</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c373t-a669590e6544841429e627b494337e388551dcdc9dd3c4921e745b0694bb8c5a3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2022</creationdate><topic>Age</topic><topic>Angiogenesis</topic><topic>Apoptosis</topic><topic>Asian people</topic><topic>Biochemistry</topic><topic>Cervical cancer</topic><topic>Endothelial cells</topic><topic>Extracellular matrix</topic><topic>Gene expression</topic><topic>Gene polymorphism</topic><topic>Genotype</topic><topic>Genotypes</topic><topic>Humans</topic><topic>Liver cancer</topic><topic>Male</topic><topic>Matrix metalloproteinase</topic><topic>Matrix metalloproteinases</topic><topic>Medical prognosis</topic><topic>Metalloproteases - genetics</topic><topic>Metalloproteinase</topic><topic>Multivariate analysis</topic><topic>Polymerase chain reaction</topic><topic>Polymorphism</topic><topic>Polymorphism, Genetic</topic><topic>Prostate cancer</topic><topic>Prostate-Specific Antigen</topic><topic>Prostatic Neoplasms - genetics</topic><topic>Prostatic Neoplasms - pathology</topic><topic>Seminal vesicle</topic><topic>Software</topic><topic>Tissue inhibitor of metalloproteinase 3</topic><topic>Tissue Inhibitor of Metalloproteinase-3 - genetics</topic><topic>Tumors</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Hsieh, Chun-Yu</creatorcontrib><creatorcontrib>Lin, Chia-Yen</creatorcontrib><creatorcontrib>Wang, Shian-Shiang</creatorcontrib><creatorcontrib>Chou, Ying-Erh</creatorcontrib><creatorcontrib>Chien, Ming-Hsien</creatorcontrib><creatorcontrib>Wen, Yu-Ching</creatorcontrib><creatorcontrib>Hsieh, Ming-Ju</creatorcontrib><creatorcontrib>Yang, Shun-Fa</creatorcontrib><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>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>Public Health Database</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 Essentials</collection><collection>ProQuest Central</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 Health & Medical Complete (Alumni)</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical 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>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>International journal of environmental research and public health</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Hsieh, Chun-Yu</au><au>Lin, Chia-Yen</au><au>Wang, Shian-Shiang</au><au>Chou, Ying-Erh</au><au>Chien, Ming-Hsien</au><au>Wen, Yu-Ching</au><au>Hsieh, Ming-Ju</au><au>Yang, Shun-Fa</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Impact of Clinicopathological Characteristics and Tissue Inhibitor of Metalloproteinase-3 Polymorphism Rs9619311 on Biochemical Recurrence in Taiwanese Patients with Prostate Cancer</atitle><jtitle>International journal of environmental research and public health</jtitle><addtitle>Int J Environ Res Public Health</addtitle><date>2022-12-25</date><risdate>2022</risdate><volume>20</volume><issue>1</issue><spage>306</spage><pages>306-</pages><issn>1660-4601</issn><issn>1661-7827</issn><eissn>1660-4601</eissn><abstract>The tissue inhibitors of metalloproteinases-3 (TIMP3) are not only endogenous regulators of matrix metalloproteinases (MMPs), but also induce apoptosis and inhibit endothelial cell migration and angiogenesis. The focus of this study was to investigate the relationship between TIMP3 genetic polymorphisms and biochemical recurrence and clinicopathological features of prostate cancer. The TIMP3 rs9619311, rs9862, and rs11547635 genetic polymorphisms were analyzed by real-time polymerase chain reaction to determine their genotypic distributions in 579 patients with prostate cancer. This study found that individuals with the TIMP3 rs9619311 TC or TC + CC genotypes have a significantly higher risk of biochemical recurrence of prostate cancer (
= 0.036 and 0.033, respectively). Moreover, in the multivariate analysis, our results showed that pathologic Gleason grade, pathologic T stage, seminal vesicle invasion, lymphovascular invasion, and TIMP3 rs9619311 were associated with increased odds of biochemical recurrence. Patients with a PSA concentration under 7 ng/mL that were found to have the TIMP3 rs9619311 genetic polymorphism were associated with Gleason total score upgrade (
= 0.012) and grade group upgrade (
= 0.023). Compared with the CC homozygous, the TIMP3 rs9862 CT + TT polymorphic variant was found to be associated with clinically advanced tumor stage (
= 0.030) and Gleason total score upgrade (
= 0.002) in prostate cancer patients. In conclusion, the results of our study demonstrated that the TIMP3 rs9619311 genetic polymorphism was significantly associated with susceptibility to biochemical recurrence of prostate cancer. TIMP3 genetic polymorphisms, especially rs9619311, can serve as key predictors of biochemical recurrence and disease prognosis of prostate cancer.</abstract><cop>Switzerland</cop><pub>MDPI AG</pub><pmid>36612628</pmid><doi>10.3390/ijerph20010306</doi><orcidid>https://orcid.org/0000-0002-0084-7231</orcidid><orcidid>https://orcid.org/0000-0002-6303-2187</orcidid><orcidid>https://orcid.org/0000-0003-3032-0198</orcidid><orcidid>https://orcid.org/0000-0001-9726-3234</orcidid><orcidid>https://orcid.org/0000-0002-0365-7927</orcidid><oa>free_for_read</oa></addata></record> |
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| subjects | Age Angiogenesis Apoptosis Asian people Biochemistry Cervical cancer Endothelial cells Extracellular matrix Gene expression Gene polymorphism Genotype Genotypes Humans Liver cancer Male Matrix metalloproteinase Matrix metalloproteinases Medical prognosis Metalloproteases - genetics Metalloproteinase Multivariate analysis Polymerase chain reaction Polymorphism Polymorphism, Genetic Prostate cancer Prostate-Specific Antigen Prostatic Neoplasms - genetics Prostatic Neoplasms - pathology Seminal vesicle Software Tissue inhibitor of metalloproteinase 3 Tissue Inhibitor of Metalloproteinase-3 - genetics Tumors |
| title | Impact of Clinicopathological Characteristics and Tissue Inhibitor of Metalloproteinase-3 Polymorphism Rs9619311 on Biochemical Recurrence in Taiwanese Patients with Prostate Cancer |
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