The gene expression profile of inflammatory, hypoxic and metabolic genes predicts the metastatic spread of human head and neck squamous cell carcinoma
Summary Objectives To assess the prognostic value of the expression profile of the main genes implicated in hypoxia, glucose and lactate metabolism, inflammation, angiogenesis and extracellular matrix interactions for the metastatic spread of head and neck squamous cell carcinoma. Patients and metho...
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| Veröffentlicht in: | Oral oncology 2014-03, Vol.50 (3), p.200-207 |
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| creator | Clatot, Florian Gouérant, Sophie Mareschal, Sylvain Cornic, Marie Berghian, Anca Choussy, Olivier El Ouakif, Faissal François, Arnaud Bénard, Magalie Ruminy, Philippe Picquenot, Jean-Michel Jardin, Fabrice |
| description | Summary Objectives To assess the prognostic value of the expression profile of the main genes implicated in hypoxia, glucose and lactate metabolism, inflammation, angiogenesis and extracellular matrix interactions for the metastatic spread of head and neck squamous cell carcinoma. Patients and methods Using a high-throughput qRT-PCR, we performed an unsupervised clustering analysis based on the expression of 42 genes for 61 patients. Usual prognostic factors and clustering analysis results were related to metastasis free survival. Results With a median follow-up of 48 months, 19 patients died from a metastatic evolution of their head and neck squamous cell carcinoma and one from a local recurrence. The unsupervised clustering analysis distinguished two groups of genes that were related to metastatic evolution. A capsular rupture ( p = 0.005) and the “cluster CXCL12 low” ( p = 0.002) were found to be independent prognostic factors for metastasis free survival. Using a Linear Predictive Score methodology, we established a 9-gene model (VHL, PTGER4, HK1, SLC16A4, DLL4, CXCL12, CXCR4, PTGER3 and CA9) that was capable of classifying the samples into the 2 clusters with 90% accuracy. Conclusion In this cohort, our clustering analysis underlined the independent prognostic value of the expression of a panel of genes involved in hypoxia and tumor environment. It allowed us to define a 9-gene model which can be applied routinely to classify newly diagnosed head and neck squamous cell carcinoma. If confirmed by an independent prospective study, this approach may help future clinical management of these aggressive tumors. |
| doi_str_mv | 10.1016/j.oraloncology.2013.12.009 |
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Patients and methods Using a high-throughput qRT-PCR, we performed an unsupervised clustering analysis based on the expression of 42 genes for 61 patients. Usual prognostic factors and clustering analysis results were related to metastasis free survival. Results With a median follow-up of 48 months, 19 patients died from a metastatic evolution of their head and neck squamous cell carcinoma and one from a local recurrence. The unsupervised clustering analysis distinguished two groups of genes that were related to metastatic evolution. A capsular rupture ( p = 0.005) and the “cluster CXCL12 low” ( p = 0.002) were found to be independent prognostic factors for metastasis free survival. Using a Linear Predictive Score methodology, we established a 9-gene model (VHL, PTGER4, HK1, SLC16A4, DLL4, CXCL12, CXCR4, PTGER3 and CA9) that was capable of classifying the samples into the 2 clusters with 90% accuracy. Conclusion In this cohort, our clustering analysis underlined the independent prognostic value of the expression of a panel of genes involved in hypoxia and tumor environment. It allowed us to define a 9-gene model which can be applied routinely to classify newly diagnosed head and neck squamous cell carcinoma. If confirmed by an independent prospective study, this approach may help future clinical management of these aggressive tumors.</description><identifier>ISSN: 1368-8375</identifier><identifier>EISSN: 1879-0593</identifier><identifier>DOI: 10.1016/j.oraloncology.2013.12.009</identifier><identifier>PMID: 24387976</identifier><language>eng</language><publisher>Kidlington: Elsevier Ltd</publisher><subject>Adult ; Aged ; Aged, 80 and over ; Biochemistry, Molecular Biology ; Biological and medical sciences ; Blood Glucose - genetics ; Blood Glucose - metabolism ; Cancer ; Carcinoma, Squamous Cell - genetics ; Carcinoma, Squamous Cell - secondary ; Clustering analysis ; CXCL12 ; CXCR4 ; Extracellular Matrix - genetics ; Female ; Gene Expression Profiling ; Genomics ; Head and Neck Neoplasms - genetics ; Head and Neck Neoplasms - pathology ; Head and neck squamous cell carcinoma ; Hematology, Oncology and Palliative Medicine ; Humans ; Hypoxia - genetics ; Lactic Acid - metabolism ; Life Sciences ; Lymphatic Metastasis - genetics ; Male ; Medical sciences ; Metastasis ; Middle Aged ; Multiple tumors. Solid tumors. Tumors in childhood (general aspects) ; Neoplasm Recurrence, Local - genetics ; Oral cancer ; Otolaryngology ; Otorhinolaryngology (head neck, general aspects and miscellaneous) ; Otorhinolaryngology. Stomatology ; Polymerase Chain Reaction ; Prognosis ; RNA - genetics ; Survival ; Tumors ; Upper respiratory tract, upper alimentary tract, paranasal sinuses, salivary glands: diseases, semeiology</subject><ispartof>Oral oncology, 2014-03, Vol.50 (3), p.200-207</ispartof><rights>Elsevier Ltd</rights><rights>2013 Elsevier Ltd</rights><rights>2015 INIST-CNRS</rights><rights>Copyright © 2013 Elsevier Ltd. All rights reserved.</rights><rights>Distributed under a Creative Commons Attribution 4.0 International License</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c532t-2befe79298b743c9329d9d8b3e408550243bff9fce0c8459011ca42a4c068d533</citedby><cites>FETCH-LOGICAL-c532t-2befe79298b743c9329d9d8b3e408550243bff9fce0c8459011ca42a4c068d533</cites><orcidid>0000-0002-7074-9282</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.sciencedirect.com/science/article/pii/S1368837513007975$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>230,314,776,780,881,3537,27901,27902,65306</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=28348335$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/24387976$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink><backlink>$$Uhttps://normandie-univ.hal.science/hal-02317983$$DView record in HAL$$Hfree_for_read</backlink></links><search><creatorcontrib>Clatot, Florian</creatorcontrib><creatorcontrib>Gouérant, Sophie</creatorcontrib><creatorcontrib>Mareschal, Sylvain</creatorcontrib><creatorcontrib>Cornic, Marie</creatorcontrib><creatorcontrib>Berghian, Anca</creatorcontrib><creatorcontrib>Choussy, Olivier</creatorcontrib><creatorcontrib>El Ouakif, Faissal</creatorcontrib><creatorcontrib>François, Arnaud</creatorcontrib><creatorcontrib>Bénard, Magalie</creatorcontrib><creatorcontrib>Ruminy, Philippe</creatorcontrib><creatorcontrib>Picquenot, Jean-Michel</creatorcontrib><creatorcontrib>Jardin, Fabrice</creatorcontrib><title>The gene expression profile of inflammatory, hypoxic and metabolic genes predicts the metastatic spread of human head and neck squamous cell carcinoma</title><title>Oral oncology</title><addtitle>Oral Oncol</addtitle><description>Summary Objectives To assess the prognostic value of the expression profile of the main genes implicated in hypoxia, glucose and lactate metabolism, inflammation, angiogenesis and extracellular matrix interactions for the metastatic spread of head and neck squamous cell carcinoma. Patients and methods Using a high-throughput qRT-PCR, we performed an unsupervised clustering analysis based on the expression of 42 genes for 61 patients. Usual prognostic factors and clustering analysis results were related to metastasis free survival. Results With a median follow-up of 48 months, 19 patients died from a metastatic evolution of their head and neck squamous cell carcinoma and one from a local recurrence. The unsupervised clustering analysis distinguished two groups of genes that were related to metastatic evolution. A capsular rupture ( p = 0.005) and the “cluster CXCL12 low” ( p = 0.002) were found to be independent prognostic factors for metastasis free survival. Using a Linear Predictive Score methodology, we established a 9-gene model (VHL, PTGER4, HK1, SLC16A4, DLL4, CXCL12, CXCR4, PTGER3 and CA9) that was capable of classifying the samples into the 2 clusters with 90% accuracy. Conclusion In this cohort, our clustering analysis underlined the independent prognostic value of the expression of a panel of genes involved in hypoxia and tumor environment. It allowed us to define a 9-gene model which can be applied routinely to classify newly diagnosed head and neck squamous cell carcinoma. If confirmed by an independent prospective study, this approach may help future clinical management of these aggressive tumors.</description><subject>Adult</subject><subject>Aged</subject><subject>Aged, 80 and over</subject><subject>Biochemistry, Molecular Biology</subject><subject>Biological and medical sciences</subject><subject>Blood Glucose - genetics</subject><subject>Blood Glucose - metabolism</subject><subject>Cancer</subject><subject>Carcinoma, Squamous Cell - genetics</subject><subject>Carcinoma, Squamous Cell - secondary</subject><subject>Clustering analysis</subject><subject>CXCL12</subject><subject>CXCR4</subject><subject>Extracellular Matrix - genetics</subject><subject>Female</subject><subject>Gene Expression Profiling</subject><subject>Genomics</subject><subject>Head and Neck Neoplasms - genetics</subject><subject>Head and Neck Neoplasms - pathology</subject><subject>Head and neck squamous cell carcinoma</subject><subject>Hematology, Oncology and Palliative Medicine</subject><subject>Humans</subject><subject>Hypoxia - genetics</subject><subject>Lactic Acid - metabolism</subject><subject>Life Sciences</subject><subject>Lymphatic Metastasis - genetics</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Metastasis</subject><subject>Middle Aged</subject><subject>Multiple tumors. Solid tumors. Tumors in childhood (general aspects)</subject><subject>Neoplasm Recurrence, Local - genetics</subject><subject>Oral cancer</subject><subject>Otolaryngology</subject><subject>Otorhinolaryngology (head neck, general aspects and miscellaneous)</subject><subject>Otorhinolaryngology. Stomatology</subject><subject>Polymerase Chain Reaction</subject><subject>Prognosis</subject><subject>RNA - genetics</subject><subject>Survival</subject><subject>Tumors</subject><subject>Upper respiratory tract, upper alimentary tract, paranasal sinuses, salivary glands: diseases, semeiology</subject><issn>1368-8375</issn><issn>1879-0593</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2014</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqNUttu1DAUjBCIloVfQBYSEkhssOM4sXlAqsqlSCvxQHm2HOek8daxt3ZSdX-E78XWLgXxAk--nJk54zMuihcElwST5u229EFZ77S3_mpfVpjQklQlxuJBcUp4K9aYCfow7WnD15y27KR4EuMWY8wIw4-Lk6qmCdY2p8WPyxHQFThAcLcLEKPxDu2CH4wF5Adk3GDVNKnZh_0bNO53_s5opFyPJphV5206ZXpMJOiNniOak2IuxlnNqRpTQfVZa1wm5dCYT1nAgb5G8WZRk18i0mAt0ipo4_yknhaPBmUjPDuuq-L7p4-X5xfrzdfPX87PNmvNaDWvqw4GaEUleNfWVAtaiV70vKNQY84YTu_shkEMGrDmNROYEK3qStUaN7xnlK6K1wfdUVm5C2ZSYS-9MvLibCPzHa4oaQWntyRhXx2waTw3C8RZTiZm28pBeoEkTYNrXBPC_g2thSAU5-RWxbsDVAcfY4Dh3gbBMsctt_LPuGUmSVLJFHciPz_2WboJ-nvqr3wT4OURoKJWdgjKaRN_4zitOaXZ8IcDDtKwbw0EGbUBp1OkAfQse2_-z8_7v2S0Nc6kztewh7j1S3ApTklkTAT5LX_Q_D_TLHDyy-hP9cnl9w</recordid><startdate>20140301</startdate><enddate>20140301</enddate><creator>Clatot, Florian</creator><creator>Gouérant, Sophie</creator><creator>Mareschal, Sylvain</creator><creator>Cornic, Marie</creator><creator>Berghian, Anca</creator><creator>Choussy, Olivier</creator><creator>El Ouakif, Faissal</creator><creator>François, Arnaud</creator><creator>Bénard, Magalie</creator><creator>Ruminy, Philippe</creator><creator>Picquenot, Jean-Michel</creator><creator>Jardin, Fabrice</creator><general>Elsevier Ltd</general><general>Elsevier</general><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>7X8</scope><scope>8FD</scope><scope>FR3</scope><scope>P64</scope><scope>RC3</scope><scope>1XC</scope><orcidid>https://orcid.org/0000-0002-7074-9282</orcidid></search><sort><creationdate>20140301</creationdate><title>The gene expression profile of inflammatory, hypoxic and metabolic genes predicts the metastatic spread of human head and neck squamous cell carcinoma</title><author>Clatot, Florian ; Gouérant, Sophie ; Mareschal, Sylvain ; Cornic, Marie ; Berghian, Anca ; Choussy, Olivier ; El Ouakif, Faissal ; François, Arnaud ; Bénard, Magalie ; Ruminy, Philippe ; Picquenot, Jean-Michel ; Jardin, Fabrice</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c532t-2befe79298b743c9329d9d8b3e408550243bff9fce0c8459011ca42a4c068d533</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2014</creationdate><topic>Adult</topic><topic>Aged</topic><topic>Aged, 80 and over</topic><topic>Biochemistry, Molecular Biology</topic><topic>Biological and medical sciences</topic><topic>Blood Glucose - genetics</topic><topic>Blood Glucose - metabolism</topic><topic>Cancer</topic><topic>Carcinoma, Squamous Cell - genetics</topic><topic>Carcinoma, Squamous Cell - secondary</topic><topic>Clustering analysis</topic><topic>CXCL12</topic><topic>CXCR4</topic><topic>Extracellular Matrix - genetics</topic><topic>Female</topic><topic>Gene Expression Profiling</topic><topic>Genomics</topic><topic>Head and Neck Neoplasms - genetics</topic><topic>Head and Neck Neoplasms - pathology</topic><topic>Head and neck squamous cell carcinoma</topic><topic>Hematology, Oncology and Palliative Medicine</topic><topic>Humans</topic><topic>Hypoxia - genetics</topic><topic>Lactic Acid - metabolism</topic><topic>Life Sciences</topic><topic>Lymphatic Metastasis - genetics</topic><topic>Male</topic><topic>Medical sciences</topic><topic>Metastasis</topic><topic>Middle Aged</topic><topic>Multiple tumors. Solid tumors. Tumors in childhood (general aspects)</topic><topic>Neoplasm Recurrence, Local - genetics</topic><topic>Oral cancer</topic><topic>Otolaryngology</topic><topic>Otorhinolaryngology (head neck, general aspects and miscellaneous)</topic><topic>Otorhinolaryngology. Stomatology</topic><topic>Polymerase Chain Reaction</topic><topic>Prognosis</topic><topic>RNA - genetics</topic><topic>Survival</topic><topic>Tumors</topic><topic>Upper respiratory tract, upper alimentary tract, paranasal sinuses, salivary glands: diseases, semeiology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Clatot, Florian</creatorcontrib><creatorcontrib>Gouérant, Sophie</creatorcontrib><creatorcontrib>Mareschal, Sylvain</creatorcontrib><creatorcontrib>Cornic, Marie</creatorcontrib><creatorcontrib>Berghian, Anca</creatorcontrib><creatorcontrib>Choussy, Olivier</creatorcontrib><creatorcontrib>El Ouakif, Faissal</creatorcontrib><creatorcontrib>François, Arnaud</creatorcontrib><creatorcontrib>Bénard, Magalie</creatorcontrib><creatorcontrib>Ruminy, Philippe</creatorcontrib><creatorcontrib>Picquenot, Jean-Michel</creatorcontrib><creatorcontrib>Jardin, Fabrice</creatorcontrib><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>MEDLINE - Academic</collection><collection>Technology Research Database</collection><collection>Engineering Research Database</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Genetics Abstracts</collection><collection>Hyper Article en Ligne (HAL)</collection><jtitle>Oral oncology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Clatot, Florian</au><au>Gouérant, Sophie</au><au>Mareschal, Sylvain</au><au>Cornic, Marie</au><au>Berghian, Anca</au><au>Choussy, Olivier</au><au>El Ouakif, Faissal</au><au>François, Arnaud</au><au>Bénard, Magalie</au><au>Ruminy, Philippe</au><au>Picquenot, Jean-Michel</au><au>Jardin, Fabrice</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>The gene expression profile of inflammatory, hypoxic and metabolic genes predicts the metastatic spread of human head and neck squamous cell carcinoma</atitle><jtitle>Oral oncology</jtitle><addtitle>Oral Oncol</addtitle><date>2014-03-01</date><risdate>2014</risdate><volume>50</volume><issue>3</issue><spage>200</spage><epage>207</epage><pages>200-207</pages><issn>1368-8375</issn><eissn>1879-0593</eissn><abstract>Summary Objectives To assess the prognostic value of the expression profile of the main genes implicated in hypoxia, glucose and lactate metabolism, inflammation, angiogenesis and extracellular matrix interactions for the metastatic spread of head and neck squamous cell carcinoma. Patients and methods Using a high-throughput qRT-PCR, we performed an unsupervised clustering analysis based on the expression of 42 genes for 61 patients. Usual prognostic factors and clustering analysis results were related to metastasis free survival. Results With a median follow-up of 48 months, 19 patients died from a metastatic evolution of their head and neck squamous cell carcinoma and one from a local recurrence. The unsupervised clustering analysis distinguished two groups of genes that were related to metastatic evolution. A capsular rupture ( p = 0.005) and the “cluster CXCL12 low” ( p = 0.002) were found to be independent prognostic factors for metastasis free survival. Using a Linear Predictive Score methodology, we established a 9-gene model (VHL, PTGER4, HK1, SLC16A4, DLL4, CXCL12, CXCR4, PTGER3 and CA9) that was capable of classifying the samples into the 2 clusters with 90% accuracy. Conclusion In this cohort, our clustering analysis underlined the independent prognostic value of the expression of a panel of genes involved in hypoxia and tumor environment. It allowed us to define a 9-gene model which can be applied routinely to classify newly diagnosed head and neck squamous cell carcinoma. If confirmed by an independent prospective study, this approach may help future clinical management of these aggressive tumors.</abstract><cop>Kidlington</cop><pub>Elsevier Ltd</pub><pmid>24387976</pmid><doi>10.1016/j.oraloncology.2013.12.009</doi><tpages>8</tpages><orcidid>https://orcid.org/0000-0002-7074-9282</orcidid></addata></record> |
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| ispartof | Oral oncology, 2014-03, Vol.50 (3), p.200-207 |
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| subjects | Adult Aged Aged, 80 and over Biochemistry, Molecular Biology Biological and medical sciences Blood Glucose - genetics Blood Glucose - metabolism Cancer Carcinoma, Squamous Cell - genetics Carcinoma, Squamous Cell - secondary Clustering analysis CXCL12 CXCR4 Extracellular Matrix - genetics Female Gene Expression Profiling Genomics Head and Neck Neoplasms - genetics Head and Neck Neoplasms - pathology Head and neck squamous cell carcinoma Hematology, Oncology and Palliative Medicine Humans Hypoxia - genetics Lactic Acid - metabolism Life Sciences Lymphatic Metastasis - genetics Male Medical sciences Metastasis Middle Aged Multiple tumors. Solid tumors. Tumors in childhood (general aspects) Neoplasm Recurrence, Local - genetics Oral cancer Otolaryngology Otorhinolaryngology (head neck, general aspects and miscellaneous) Otorhinolaryngology. Stomatology Polymerase Chain Reaction Prognosis RNA - genetics Survival Tumors Upper respiratory tract, upper alimentary tract, paranasal sinuses, salivary glands: diseases, semeiology |
| title | The gene expression profile of inflammatory, hypoxic and metabolic genes predicts the metastatic spread of human head and neck squamous cell carcinoma |
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