The Co-Expression of Kallikrein 5 and Kallikrein 7 Associates with Poor Survival in Non-HPV Oral Squamous-Cell Carcinoma
Objective: Oral squamous-cell carcinoma (OSCC) still has a poor prognosis. Lymph node metastasis (LNM) is a major determinant of treatment decisions and prognosis. Serine protease inhibitor Kazal-type 5 (SPINK5) is the inhibitor of kallikrein 5 (KLK5) and KLK7. SPINK5, KLK5 and KLK7 are three of the...
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| Veröffentlicht in: | Pathobiology (Basel) 2015-01, Vol.82 (2), p.58-67 |
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| creator | Leusink, Frank K.J. van Diest, P.J. Frank, M.H. Broekhuizen, R. Braunius, W. van Hooff, S.R. Willems, Stefan M. Koole, R. |
| description | Objective: Oral squamous-cell carcinoma (OSCC) still has a poor prognosis. Lymph node metastasis (LNM) is a major determinant of treatment decisions and prognosis. Serine protease inhibitor Kazal-type 5 (SPINK5) is the inhibitor of kallikrein 5 (KLK5) and KLK7. SPINK5, KLK5 and KLK7 are three of the genes of a recently validated LNM-predicting gene expression profile in OSCC. This study evaluates their clinicopathological role and value as biomarkers in OSCC. Methods: Eighty-three patients with primary OSCC, treated surgically between 1996 and 2000, were included. Gene expression data were acquired from a previously reported study. Human papillomavirus (HPV) status was determined by an algorithm for HPV-16. Protein expression for KLK5, KLK7 and SPINK5 was semi-quantitatively determined in all 83 tumours by immunohistochemistry. All expression data were correlated with clinicopathological parameters. Results: Concurrent loss of KLK5 and KLK7 correlates with worse disease-specific and overall survival (DSS and OS). Multivariate analysis proved that co-expression is an independent prognostic factor for DSS (p = 0.029) and OS (p = 0.001). Conclusion: This report demonstrates that concurrent loss of KLK5 and KLK7 associates with a poor clinical outcome in OSCC and could therefore serve as prognostic marker in this disease. |
| doi_str_mv | 10.1159/000381904 |
| format | Article |
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Lymph node metastasis (LNM) is a major determinant of treatment decisions and prognosis. Serine protease inhibitor Kazal-type 5 (SPINK5) is the inhibitor of kallikrein 5 (KLK5) and KLK7. SPINK5, KLK5 and KLK7 are three of the genes of a recently validated LNM-predicting gene expression profile in OSCC. This study evaluates their clinicopathological role and value as biomarkers in OSCC. Methods: Eighty-three patients with primary OSCC, treated surgically between 1996 and 2000, were included. Gene expression data were acquired from a previously reported study. Human papillomavirus (HPV) status was determined by an algorithm for HPV-16. Protein expression for KLK5, KLK7 and SPINK5 was semi-quantitatively determined in all 83 tumours by immunohistochemistry. All expression data were correlated with clinicopathological parameters. Results: Concurrent loss of KLK5 and KLK7 correlates with worse disease-specific and overall survival (DSS and OS). Multivariate analysis proved that co-expression is an independent prognostic factor for DSS (p = 0.029) and OS (p = 0.001). Conclusion: This report demonstrates that concurrent loss of KLK5 and KLK7 associates with a poor clinical outcome in OSCC and could therefore serve as prognostic marker in this disease.</description><identifier>ISSN: 1015-2008</identifier><identifier>EISSN: 1423-0291</identifier><identifier>DOI: 10.1159/000381904</identifier><identifier>PMID: 26022646</identifier><identifier>CODEN: PATHEF</identifier><language>eng</language><publisher>Basel, Switzerland: S. Karger AG</publisher><subject>Adult ; Aged ; Aged, 80 and over ; Biomarkers, Tumor - genetics ; Biomarkers, Tumor - isolation & purification ; Carcinoma, Squamous Cell - genetics ; Carcinoma, Squamous Cell - mortality ; Carcinoma, Squamous Cell - virology ; Female ; Gene Expression Regulation, Neoplastic ; Head & neck cancer ; Human papillomavirus ; Human papillomavirus 16 - isolation & purification ; Humans ; Kallikreins - genetics ; Lymphatic system ; Male ; Metastasis ; Middle Aged ; Mouth Neoplasms - genetics ; Mouth Neoplasms - mortality ; Multivariate analysis ; Original Paper ; Prognosis ; Protease inhibitors ; Proteinase inhibitors ; Survival Rate</subject><ispartof>Pathobiology (Basel), 2015-01, Vol.82 (2), p.58-67</ispartof><rights>2015 S. Karger AG, Basel</rights><rights>Copyright (c) 2015 S. Karger AG, Basel</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c430t-6d790a189e2c252967c35082ea8281c4db327360d27105b21870498ec911c0603</citedby><cites>FETCH-LOGICAL-c430t-6d790a189e2c252967c35082ea8281c4db327360d27105b21870498ec911c0603</cites><orcidid>0000-0001-5852-2571</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780,2423,27901,27902</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/26022646$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Leusink, Frank K.J.</creatorcontrib><creatorcontrib>van Diest, P.J.</creatorcontrib><creatorcontrib>Frank, M.H.</creatorcontrib><creatorcontrib>Broekhuizen, R.</creatorcontrib><creatorcontrib>Braunius, W.</creatorcontrib><creatorcontrib>van Hooff, S.R.</creatorcontrib><creatorcontrib>Willems, Stefan M.</creatorcontrib><creatorcontrib>Koole, R.</creatorcontrib><title>The Co-Expression of Kallikrein 5 and Kallikrein 7 Associates with Poor Survival in Non-HPV Oral Squamous-Cell Carcinoma</title><title>Pathobiology (Basel)</title><addtitle>Pathobiology</addtitle><description>Objective: Oral squamous-cell carcinoma (OSCC) still has a poor prognosis. Lymph node metastasis (LNM) is a major determinant of treatment decisions and prognosis. Serine protease inhibitor Kazal-type 5 (SPINK5) is the inhibitor of kallikrein 5 (KLK5) and KLK7. SPINK5, KLK5 and KLK7 are three of the genes of a recently validated LNM-predicting gene expression profile in OSCC. This study evaluates their clinicopathological role and value as biomarkers in OSCC. Methods: Eighty-three patients with primary OSCC, treated surgically between 1996 and 2000, were included. Gene expression data were acquired from a previously reported study. Human papillomavirus (HPV) status was determined by an algorithm for HPV-16. Protein expression for KLK5, KLK7 and SPINK5 was semi-quantitatively determined in all 83 tumours by immunohistochemistry. All expression data were correlated with clinicopathological parameters. Results: Concurrent loss of KLK5 and KLK7 correlates with worse disease-specific and overall survival (DSS and OS). Multivariate analysis proved that co-expression is an independent prognostic factor for DSS (p = 0.029) and OS (p = 0.001). Conclusion: This report demonstrates that concurrent loss of KLK5 and KLK7 associates with a poor clinical outcome in OSCC and could therefore serve as prognostic marker in this disease.</description><subject>Adult</subject><subject>Aged</subject><subject>Aged, 80 and over</subject><subject>Biomarkers, Tumor - genetics</subject><subject>Biomarkers, Tumor - isolation & purification</subject><subject>Carcinoma, Squamous Cell - genetics</subject><subject>Carcinoma, Squamous Cell - mortality</subject><subject>Carcinoma, Squamous Cell - virology</subject><subject>Female</subject><subject>Gene Expression Regulation, Neoplastic</subject><subject>Head & neck cancer</subject><subject>Human papillomavirus</subject><subject>Human papillomavirus 16 - isolation & purification</subject><subject>Humans</subject><subject>Kallikreins - genetics</subject><subject>Lymphatic system</subject><subject>Male</subject><subject>Metastasis</subject><subject>Middle Aged</subject><subject>Mouth Neoplasms - genetics</subject><subject>Mouth Neoplasms - mortality</subject><subject>Multivariate analysis</subject><subject>Original Paper</subject><subject>Prognosis</subject><subject>Protease inhibitors</subject><subject>Proteinase inhibitors</subject><subject>Survival Rate</subject><issn>1015-2008</issn><issn>1423-0291</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2015</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>BENPR</sourceid><recordid>eNqF0ctPGzEQB2CrasWrHHqvKktc4LB0bK9fx2hFSVUEkUh7XTleBwy768TOUvjvcRQaIVSJk1-ff5rRIPSFwCkhXH8HAKaIhvID2iMlZQVQTT7mPRBeUAC1i_ZTustMgYAdtEsFUCpKsYcep7cOV6E4e1xEl5IPPQ5z_Mu0rb-PzveYY9M3ry8kHqUUrDcrl_Bfv7rFkxAivh7ig38wLc7kMvTFePIHX8V8vl4OpgtDKirXtrgy0fo-dOYz-jQ3bXKHL-sB-v3jbFqNi4ur85_V6KKwJYNVIRqpwRClHbWUUy2kZRwUdUZRRWzZzBiVTEBDJQE-o0RJKLVyVhNic7PsAB1vchcxLAeXVnXnk82lmN7lqmoiFaeMSF2-T4VWWgBX69SjN_QuDLHPjeRA4FJJDiyrk42yMaQU3bxeRN-Z-FQTqNeTq7eTy_bbS-Iw61yzlf9GlcHXDbg38cbFLdj-P_rv82Q03Yh60czZM1yIo9c</recordid><startdate>20150101</startdate><enddate>20150101</enddate><creator>Leusink, Frank K.J.</creator><creator>van Diest, P.J.</creator><creator>Frank, M.H.</creator><creator>Broekhuizen, R.</creator><creator>Braunius, W.</creator><creator>van Hooff, S.R.</creator><creator>Willems, Stefan M.</creator><creator>Koole, R.</creator><general>S. 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Academic</collection><collection>Virology and AIDS Abstracts</collection><collection>AIDS and Cancer Research Abstracts</collection><jtitle>Pathobiology (Basel)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Leusink, Frank K.J.</au><au>van Diest, P.J.</au><au>Frank, M.H.</au><au>Broekhuizen, R.</au><au>Braunius, W.</au><au>van Hooff, S.R.</au><au>Willems, Stefan M.</au><au>Koole, R.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>The Co-Expression of Kallikrein 5 and Kallikrein 7 Associates with Poor Survival in Non-HPV Oral Squamous-Cell Carcinoma</atitle><jtitle>Pathobiology (Basel)</jtitle><addtitle>Pathobiology</addtitle><date>2015-01-01</date><risdate>2015</risdate><volume>82</volume><issue>2</issue><spage>58</spage><epage>67</epage><pages>58-67</pages><issn>1015-2008</issn><eissn>1423-0291</eissn><coden>PATHEF</coden><abstract>Objective: Oral squamous-cell carcinoma (OSCC) still has a poor prognosis. Lymph node metastasis (LNM) is a major determinant of treatment decisions and prognosis. Serine protease inhibitor Kazal-type 5 (SPINK5) is the inhibitor of kallikrein 5 (KLK5) and KLK7. SPINK5, KLK5 and KLK7 are three of the genes of a recently validated LNM-predicting gene expression profile in OSCC. This study evaluates their clinicopathological role and value as biomarkers in OSCC. Methods: Eighty-three patients with primary OSCC, treated surgically between 1996 and 2000, were included. Gene expression data were acquired from a previously reported study. Human papillomavirus (HPV) status was determined by an algorithm for HPV-16. Protein expression for KLK5, KLK7 and SPINK5 was semi-quantitatively determined in all 83 tumours by immunohistochemistry. All expression data were correlated with clinicopathological parameters. Results: Concurrent loss of KLK5 and KLK7 correlates with worse disease-specific and overall survival (DSS and OS). Multivariate analysis proved that co-expression is an independent prognostic factor for DSS (p = 0.029) and OS (p = 0.001). Conclusion: This report demonstrates that concurrent loss of KLK5 and KLK7 associates with a poor clinical outcome in OSCC and could therefore serve as prognostic marker in this disease.</abstract><cop>Basel, Switzerland</cop><pub>S. Karger AG</pub><pmid>26022646</pmid><doi>10.1159/000381904</doi><tpages>10</tpages><orcidid>https://orcid.org/0000-0001-5852-2571</orcidid><oa>free_for_read</oa></addata></record> |
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| source | Karger Journals; MEDLINE |
| subjects | Adult Aged Aged, 80 and over Biomarkers, Tumor - genetics Biomarkers, Tumor - isolation & purification Carcinoma, Squamous Cell - genetics Carcinoma, Squamous Cell - mortality Carcinoma, Squamous Cell - virology Female Gene Expression Regulation, Neoplastic Head & neck cancer Human papillomavirus Human papillomavirus 16 - isolation & purification Humans Kallikreins - genetics Lymphatic system Male Metastasis Middle Aged Mouth Neoplasms - genetics Mouth Neoplasms - mortality Multivariate analysis Original Paper Prognosis Protease inhibitors Proteinase inhibitors Survival Rate |
| title | The Co-Expression of Kallikrein 5 and Kallikrein 7 Associates with Poor Survival in Non-HPV Oral Squamous-Cell Carcinoma |
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