Cysteine proteinase inhibitor cystatin C in squamous cell carcinoma of the head and neck: relation to prognosis
To determine the role of the cysteine proteinase inhibitor cystatin C in the invasive behavior of squamous cell carcinoma of the head and neck (SCCHN), Cystatin C protein level was measured in 82 pairs of primary tumour tissue and adjacent noncancerous mucosa, using the enzyme-linked immunosorbent a...
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| Veröffentlicht in: | British journal of cancer 2004-05, Vol.90 (10), p.1961-1968 |
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| description | To determine the role of the cysteine proteinase inhibitor cystatin C in the invasive behavior of squamous cell carcinoma of the head and neck (SCCHN), Cystatin C protein level was measured in 82 pairs of primary tumour tissue and adjacent noncancerous mucosa, using the enzyme-linked immunosorbent assay. The median level of cystatin C in tumour tissue was 1.18 times lower than that in corresponding mucosa (
P
=0.031). In normal mucosa samples, the cystatin C level was influenced by the site of sampling: it was lower in nonlaryngeal tissue samples (oral cavity, oro- or hypopharynx) than in laryngeal samples (
P
=0.004). The tumour cystatin C level correlated inversely with pN-stage (
P
=0.047), whereas a trend of lower cystatin C levels was observed in the group with extranodal tumour extension compared to those with no extranodal spread (
P
=0.069). In univariate analysis, the patients with low tumour cystatin C levels exhibited poor disease-free survival (DFS,
P
=0.013) and disease-specific survival (DSS,
P
=0.013). In multivariate analysis, the most powerful predictor of survival was pN-stage (DFS:
P
=0.040, HR 2.78; DSS:
P
=0.011, HR 4.36,), followed by the cystatin C level (DFS:
P
=0.043, HR 0.22; DSS:
P
=0.067, HR 0.25). When comparing the prognostic strength of cystatin C to that of stefin A, another cysteine proteinase inhibitor, which emerged as the most significant prognosticator for survival in our previous study analysing the same cohort of patients, stefin A proved to be significantly more reliable predictor for both DFS and DSS than cystatin C. Our results indicate that cystatin C is implicated in the invasive behavior of SCCHN, and that there are variations in regulation of proteolytic pathways under nonmalignant conditions, inherent to individual subsites inside the upper aerodigestive tract. The correlation between high cystatin C levels and improved survival concurs with the concept of the protective role of high levels of cysteine proteinase inhibitors in tissue homogenates that has been previously suggested by the survival results in breast and lung carcinoma as well as SCCHN. |
| doi_str_mv | 10.1038/sj.bjc.6601830 |
| format | Article |
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P
=0.031). In normal mucosa samples, the cystatin C level was influenced by the site of sampling: it was lower in nonlaryngeal tissue samples (oral cavity, oro- or hypopharynx) than in laryngeal samples (
P
=0.004). The tumour cystatin C level correlated inversely with pN-stage (
P
=0.047), whereas a trend of lower cystatin C levels was observed in the group with extranodal tumour extension compared to those with no extranodal spread (
P
=0.069). In univariate analysis, the patients with low tumour cystatin C levels exhibited poor disease-free survival (DFS,
P
=0.013) and disease-specific survival (DSS,
P
=0.013). In multivariate analysis, the most powerful predictor of survival was pN-stage (DFS:
P
=0.040, HR 2.78; DSS:
P
=0.011, HR 4.36,), followed by the cystatin C level (DFS:
P
=0.043, HR 0.22; DSS:
P
=0.067, HR 0.25). When comparing the prognostic strength of cystatin C to that of stefin A, another cysteine proteinase inhibitor, which emerged as the most significant prognosticator for survival in our previous study analysing the same cohort of patients, stefin A proved to be significantly more reliable predictor for both DFS and DSS than cystatin C. Our results indicate that cystatin C is implicated in the invasive behavior of SCCHN, and that there are variations in regulation of proteolytic pathways under nonmalignant conditions, inherent to individual subsites inside the upper aerodigestive tract. The correlation between high cystatin C levels and improved survival concurs with the concept of the protective role of high levels of cysteine proteinase inhibitors in tissue homogenates that has been previously suggested by the survival results in breast and lung carcinoma as well as SCCHN.</description><identifier>ISSN: 0007-0920</identifier><identifier>EISSN: 1532-1827</identifier><identifier>DOI: 10.1038/sj.bjc.6601830</identifier><identifier>PMID: 15138478</identifier><identifier>CODEN: BJCAAI</identifier><language>eng</language><publisher>London: Nature Publishing Group UK</publisher><subject>Adult ; Aged ; Amino acids ; Biological and medical sciences ; Biomedical and Life Sciences ; Biomedicine ; Cancer Research ; Carcinoma, Squamous Cell - genetics ; Carcinoma, Squamous Cell - pathology ; Cerebrospinal Fluid Proteins ; Cohort Studies ; Cystatin C ; Cystatins - analysis ; Cystatins - metabolism ; Cystatins - pharmacology ; Cysteine Proteinase Inhibitors ; Disease-Free Survival ; Drug Resistance ; Epidemiology ; Female ; Gene Expression Regulation, Neoplastic ; Head and Neck Neoplasms - genetics ; Head and Neck Neoplasms - pathology ; Humans ; Male ; Medical prognosis ; Medical research ; Medical sciences ; Middle Aged ; Molecular and Cellular Pathology ; Molecular Medicine ; Neoplasm Invasiveness ; Oncology ; Otolaryngology ; Otorhinolaryngology (head neck, general aspects and miscellaneous) ; Otorhinolaryngology. Stomatology ; Prognosis ; Proteins ; Tumors</subject><ispartof>British journal of cancer, 2004-05, Vol.90 (10), p.1961-1968</ispartof><rights>The Author(s) 2004</rights><rights>2004 INIST-CNRS</rights><rights>Copyright Nature Publishing Group May 17, 2004</rights><rights>Copyright © 2004 Cancer Research UK 2004 Cancer Research UK</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c483t-48f771bc63145938f4c3b1ca73a45a66d43559151c639eceee587cfd8b3c374d3</citedby><cites>FETCH-LOGICAL-c483t-48f771bc63145938f4c3b1ca73a45a66d43559151c639eceee587cfd8b3c374d3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC2409457/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC2409457/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,881,27901,27902,41464,42533,51294,53766,53768</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=15774143$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/15138478$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Strojan, P</creatorcontrib><creatorcontrib>Oblak, I</creatorcontrib><creatorcontrib>Svetic, B</creatorcontrib><creatorcontrib>Šmid, L</creatorcontrib><creatorcontrib>Kos, J</creatorcontrib><title>Cysteine proteinase inhibitor cystatin C in squamous cell carcinoma of the head and neck: relation to prognosis</title><title>British journal of cancer</title><addtitle>Br J Cancer</addtitle><addtitle>Br J Cancer</addtitle><description>To determine the role of the cysteine proteinase inhibitor cystatin C in the invasive behavior of squamous cell carcinoma of the head and neck (SCCHN), Cystatin C protein level was measured in 82 pairs of primary tumour tissue and adjacent noncancerous mucosa, using the enzyme-linked immunosorbent assay. The median level of cystatin C in tumour tissue was 1.18 times lower than that in corresponding mucosa (
P
=0.031). In normal mucosa samples, the cystatin C level was influenced by the site of sampling: it was lower in nonlaryngeal tissue samples (oral cavity, oro- or hypopharynx) than in laryngeal samples (
P
=0.004). The tumour cystatin C level correlated inversely with pN-stage (
P
=0.047), whereas a trend of lower cystatin C levels was observed in the group with extranodal tumour extension compared to those with no extranodal spread (
P
=0.069). In univariate analysis, the patients with low tumour cystatin C levels exhibited poor disease-free survival (DFS,
P
=0.013) and disease-specific survival (DSS,
P
=0.013). In multivariate analysis, the most powerful predictor of survival was pN-stage (DFS:
P
=0.040, HR 2.78; DSS:
P
=0.011, HR 4.36,), followed by the cystatin C level (DFS:
P
=0.043, HR 0.22; DSS:
P
=0.067, HR 0.25). When comparing the prognostic strength of cystatin C to that of stefin A, another cysteine proteinase inhibitor, which emerged as the most significant prognosticator for survival in our previous study analysing the same cohort of patients, stefin A proved to be significantly more reliable predictor for both DFS and DSS than cystatin C. Our results indicate that cystatin C is implicated in the invasive behavior of SCCHN, and that there are variations in regulation of proteolytic pathways under nonmalignant conditions, inherent to individual subsites inside the upper aerodigestive tract. The correlation between high cystatin C levels and improved survival concurs with the concept of the protective role of high levels of cysteine proteinase inhibitors in tissue homogenates that has been previously suggested by the survival results in breast and lung carcinoma as well as SCCHN.</description><subject>Adult</subject><subject>Aged</subject><subject>Amino acids</subject><subject>Biological and medical sciences</subject><subject>Biomedical and Life Sciences</subject><subject>Biomedicine</subject><subject>Cancer Research</subject><subject>Carcinoma, Squamous Cell - genetics</subject><subject>Carcinoma, Squamous Cell - pathology</subject><subject>Cerebrospinal Fluid Proteins</subject><subject>Cohort Studies</subject><subject>Cystatin C</subject><subject>Cystatins - analysis</subject><subject>Cystatins - metabolism</subject><subject>Cystatins - pharmacology</subject><subject>Cysteine Proteinase Inhibitors</subject><subject>Disease-Free Survival</subject><subject>Drug Resistance</subject><subject>Epidemiology</subject><subject>Female</subject><subject>Gene Expression Regulation, Neoplastic</subject><subject>Head and Neck Neoplasms - genetics</subject><subject>Head and Neck Neoplasms - pathology</subject><subject>Humans</subject><subject>Male</subject><subject>Medical prognosis</subject><subject>Medical research</subject><subject>Medical sciences</subject><subject>Middle Aged</subject><subject>Molecular and Cellular Pathology</subject><subject>Molecular Medicine</subject><subject>Neoplasm Invasiveness</subject><subject>Oncology</subject><subject>Otolaryngology</subject><subject>Otorhinolaryngology (head neck, general aspects and miscellaneous)</subject><subject>Otorhinolaryngology. Stomatology</subject><subject>Prognosis</subject><subject>Proteins</subject><subject>Tumors</subject><issn>0007-0920</issn><issn>1532-1827</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2004</creationdate><recordtype>article</recordtype><sourceid>C6C</sourceid><sourceid>EIF</sourceid><sourceid>BENPR</sourceid><recordid>eNp1kUtr3DAUhUVpaSZpt10WUUh2nkiWbEldFMLQFwSySddClq9n5NrSRLIL-feVGdOkha70uN89OlcHoXeUbClh8jr126a327omVDLyAm1oxcqCylK8RBtCiCiIKskZOk-pz0dFpHiNzmhFmeRCblDYPaYJnAd8jGHZmATY-YNr3BQitrlqJufxLl_i9DCbMcwJWxgGbE20zofR4NDh6QD4AKbFxrfYg_35EUcYcmvweAqL-N6H5NIb9KozQ4K363qBfnz5fL_7Vtzeff2-u7ktLJdsKrjshKCNrRnllWKy45Y11BrBDK9MXbecVZXKY2RCgQWASgrbtbJhlgnesgv06aR7nJsRWgt-imbQx-hGEx91ME7_XfHuoPfhly45UbwSWeBqFYjhYYY06dGlZW7jIX-BFlRRUTOWwQ__gH2Yo8_D6bJUSiop6wxtT5CNIaUI3R8nlOglSJ16nYPUa5C54f1z_0_4mlwGLlfAJGuGLhpvXXrGCcEpX-xdn7iUS34P8cnef57-DRbJuNk</recordid><startdate>20040517</startdate><enddate>20040517</enddate><creator>Strojan, P</creator><creator>Oblak, I</creator><creator>Svetic, B</creator><creator>Šmid, L</creator><creator>Kos, J</creator><general>Nature Publishing Group UK</general><general>Nature Publishing Group</general><scope>C6C</scope><scope>IQODW</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>3V.</scope><scope>7RV</scope><scope>7TO</scope><scope>7U9</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AN0</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>KB0</scope><scope>LK8</scope><scope>M0S</scope><scope>M1P</scope><scope>M7P</scope><scope>NAPCQ</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>20040517</creationdate><title>Cysteine proteinase inhibitor cystatin C in squamous cell carcinoma of the head and neck: relation to prognosis</title><author>Strojan, P ; Oblak, I ; Svetic, B ; Šmid, L ; Kos, J</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c483t-48f771bc63145938f4c3b1ca73a45a66d43559151c639eceee587cfd8b3c374d3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2004</creationdate><topic>Adult</topic><topic>Aged</topic><topic>Amino acids</topic><topic>Biological and medical sciences</topic><topic>Biomedical and Life Sciences</topic><topic>Biomedicine</topic><topic>Cancer Research</topic><topic>Carcinoma, Squamous Cell - genetics</topic><topic>Carcinoma, Squamous Cell - pathology</topic><topic>Cerebrospinal Fluid Proteins</topic><topic>Cohort Studies</topic><topic>Cystatin C</topic><topic>Cystatins - analysis</topic><topic>Cystatins - metabolism</topic><topic>Cystatins - pharmacology</topic><topic>Cysteine Proteinase Inhibitors</topic><topic>Disease-Free Survival</topic><topic>Drug Resistance</topic><topic>Epidemiology</topic><topic>Female</topic><topic>Gene Expression Regulation, Neoplastic</topic><topic>Head and Neck Neoplasms - genetics</topic><topic>Head and Neck Neoplasms - pathology</topic><topic>Humans</topic><topic>Male</topic><topic>Medical prognosis</topic><topic>Medical research</topic><topic>Medical sciences</topic><topic>Middle Aged</topic><topic>Molecular and Cellular Pathology</topic><topic>Molecular Medicine</topic><topic>Neoplasm Invasiveness</topic><topic>Oncology</topic><topic>Otolaryngology</topic><topic>Otorhinolaryngology (head neck, general aspects and miscellaneous)</topic><topic>Otorhinolaryngology. Stomatology</topic><topic>Prognosis</topic><topic>Proteins</topic><topic>Tumors</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Strojan, P</creatorcontrib><creatorcontrib>Oblak, I</creatorcontrib><creatorcontrib>Svetic, B</creatorcontrib><creatorcontrib>Šmid, L</creatorcontrib><creatorcontrib>Kos, J</creatorcontrib><collection>Springer Nature OA/Free Journals</collection><collection>Pascal-Francis</collection><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>Proquest Nursing & Allied Health Source</collection><collection>Oncogenes and Growth Factors Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>Public Health Database</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Natural Science Collection</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>British Nursing Database</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Natural Science Collection</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 Central Student</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Nursing & Allied Health Database (Alumni Edition)</collection><collection>ProQuest Biological Science Collection</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Biological Science Database</collection><collection>Nursing & Allied Health Premium</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>PubMed Central (Full Participant titles)</collection><jtitle>British journal of cancer</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Strojan, P</au><au>Oblak, I</au><au>Svetic, B</au><au>Šmid, L</au><au>Kos, J</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Cysteine proteinase inhibitor cystatin C in squamous cell carcinoma of the head and neck: relation to prognosis</atitle><jtitle>British journal of cancer</jtitle><stitle>Br J Cancer</stitle><addtitle>Br J Cancer</addtitle><date>2004-05-17</date><risdate>2004</risdate><volume>90</volume><issue>10</issue><spage>1961</spage><epage>1968</epage><pages>1961-1968</pages><issn>0007-0920</issn><eissn>1532-1827</eissn><coden>BJCAAI</coden><abstract>To determine the role of the cysteine proteinase inhibitor cystatin C in the invasive behavior of squamous cell carcinoma of the head and neck (SCCHN), Cystatin C protein level was measured in 82 pairs of primary tumour tissue and adjacent noncancerous mucosa, using the enzyme-linked immunosorbent assay. The median level of cystatin C in tumour tissue was 1.18 times lower than that in corresponding mucosa (
P
=0.031). In normal mucosa samples, the cystatin C level was influenced by the site of sampling: it was lower in nonlaryngeal tissue samples (oral cavity, oro- or hypopharynx) than in laryngeal samples (
P
=0.004). The tumour cystatin C level correlated inversely with pN-stage (
P
=0.047), whereas a trend of lower cystatin C levels was observed in the group with extranodal tumour extension compared to those with no extranodal spread (
P
=0.069). In univariate analysis, the patients with low tumour cystatin C levels exhibited poor disease-free survival (DFS,
P
=0.013) and disease-specific survival (DSS,
P
=0.013). In multivariate analysis, the most powerful predictor of survival was pN-stage (DFS:
P
=0.040, HR 2.78; DSS:
P
=0.011, HR 4.36,), followed by the cystatin C level (DFS:
P
=0.043, HR 0.22; DSS:
P
=0.067, HR 0.25). When comparing the prognostic strength of cystatin C to that of stefin A, another cysteine proteinase inhibitor, which emerged as the most significant prognosticator for survival in our previous study analysing the same cohort of patients, stefin A proved to be significantly more reliable predictor for both DFS and DSS than cystatin C. Our results indicate that cystatin C is implicated in the invasive behavior of SCCHN, and that there are variations in regulation of proteolytic pathways under nonmalignant conditions, inherent to individual subsites inside the upper aerodigestive tract. The correlation between high cystatin C levels and improved survival concurs with the concept of the protective role of high levels of cysteine proteinase inhibitors in tissue homogenates that has been previously suggested by the survival results in breast and lung carcinoma as well as SCCHN.</abstract><cop>London</cop><pub>Nature Publishing Group UK</pub><pmid>15138478</pmid><doi>10.1038/sj.bjc.6601830</doi><tpages>8</tpages><oa>free_for_read</oa></addata></record> |
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| source | MEDLINE; Springer Nature - Complete Springer Journals; Nature Journals Online; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; PubMed Central |
| subjects | Adult Aged Amino acids Biological and medical sciences Biomedical and Life Sciences Biomedicine Cancer Research Carcinoma, Squamous Cell - genetics Carcinoma, Squamous Cell - pathology Cerebrospinal Fluid Proteins Cohort Studies Cystatin C Cystatins - analysis Cystatins - metabolism Cystatins - pharmacology Cysteine Proteinase Inhibitors Disease-Free Survival Drug Resistance Epidemiology Female Gene Expression Regulation, Neoplastic Head and Neck Neoplasms - genetics Head and Neck Neoplasms - pathology Humans Male Medical prognosis Medical research Medical sciences Middle Aged Molecular and Cellular Pathology Molecular Medicine Neoplasm Invasiveness Oncology Otolaryngology Otorhinolaryngology (head neck, general aspects and miscellaneous) Otorhinolaryngology. Stomatology Prognosis Proteins Tumors |
| title | Cysteine proteinase inhibitor cystatin C in squamous cell carcinoma of the head and neck: relation to prognosis |
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