Low-Level Expression of MicroRNAs let-7d and miR-205 Are Prognostic Markers of Head and Neck Squamous Cell Carcinoma
Small noncoding microRNAs (miRNAs) have been shown to be abnormally expressed in every tumor type examined. The importance of miRNAs as potential cancer prognostic indicators is underscored by their involvement in the regulation of basic cellular processes such as cell proliferation, differentiation...
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creator | Childs, Geoffrey Fazzari, Melissa Kung, Gloria Kawachi, Nicole Brandwein-Gensler, Margaret McLemore, Michael Chen, Quan Burk, Robert D Smith, Richard V Prystowsky, Michael B Belbin, Thomas J Schlecht, Nicolas F |
description | Small noncoding microRNAs (miRNAs) have been shown to be abnormally expressed in every tumor type examined. The importance of miRNAs as potential cancer prognostic indicators is underscored by their involvement in the regulation of basic cellular processes such as cell proliferation, differentiation, and apoptosis. In this study, miRNA expression profiles of head and neck squamous cell carcinoma (HNSCC) tumor and adjacent normal tissue were examined by microarray analysis and validated by quantitative TaqMan real-time polymerase chain reaction. Using TaqMan real-time polymerase chain reaction we measured the quantitative associations between a subset of miRNAs identified on microarrays in primary tumors at diagnosis and cancer survival in a cohort of 104 HNSCC patients undergoing treatment with curative intent. The majority of miRNAs exhibiting altered expression in primary human HNSCC tumors (including miR-1 , miR-133a , miR-205 , and let-7d ) show lower expression levels relative to normal adjacent tissue. In contrast, hsa-miR-21 is frequently overexpressed in human HNSCC tumors. Using univariate and multivariable statistical models we show that low levels of hsa-miR205 are significantly associated with loco-regional recurrence independent of disease severity at diagnosis and treatment. In addition, combined low levels of hsa-miR-205 and hsa-let-7d expression in HNSCC tumors are significantly associated with poor head and neck cancer survival Our results show that miRNA expression levels can be used as prognostic markers of head and neck cancer. |
doi_str_mv | 10.2353/ajpath.2009.080731 |
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The importance of miRNAs as potential cancer prognostic indicators is underscored by their involvement in the regulation of basic cellular processes such as cell proliferation, differentiation, and apoptosis. In this study, miRNA expression profiles of head and neck squamous cell carcinoma (HNSCC) tumor and adjacent normal tissue were examined by microarray analysis and validated by quantitative TaqMan real-time polymerase chain reaction. Using TaqMan real-time polymerase chain reaction we measured the quantitative associations between a subset of miRNAs identified on microarrays in primary tumors at diagnosis and cancer survival in a cohort of 104 HNSCC patients undergoing treatment with curative intent. The majority of miRNAs exhibiting altered expression in primary human HNSCC tumors (including miR-1 , miR-133a , miR-205 , and let-7d ) show lower expression levels relative to normal adjacent tissue. In contrast, hsa-miR-21 is frequently overexpressed in human HNSCC tumors. Using univariate and multivariable statistical models we show that low levels of hsa-miR205 are significantly associated with loco-regional recurrence independent of disease severity at diagnosis and treatment. In addition, combined low levels of hsa-miR-205 and hsa-let-7d expression in HNSCC tumors are significantly associated with poor head and neck cancer survival Our results show that miRNA expression levels can be used as prognostic markers of head and neck cancer.</description><identifier>ISSN: 0002-9440</identifier><identifier>EISSN: 1525-2191</identifier><identifier>DOI: 10.2353/ajpath.2009.080731</identifier><identifier>PMID: 19179615</identifier><identifier>CODEN: AJPAA4</identifier><language>eng</language><publisher>Bethesda, MD: Elsevier Inc</publisher><subject>Biological and medical sciences ; Carcinoma, Squamous Cell - genetics ; Carcinoma, Squamous Cell - mortality ; Carcinoma, Squamous Cell - pathology ; Female ; Gene Expression Regulation, Neoplastic ; Head and Neck Neoplasms - genetics ; Head and Neck Neoplasms - mortality ; Head and Neck Neoplasms - pathology ; Humans ; Investigative techniques, diagnostic techniques (general aspects) ; Male ; Medical sciences ; MicroRNAs - genetics ; MicroRNAs - isolation & purification ; Middle Aged ; Neoplasm Staging ; Otorhinolaryngology (head neck, general aspects and miscellaneous) ; Otorhinolaryngology. Stomatology ; Pathology ; Pathology. Cytology. Biochemistry. Spectrometry. Miscellaneous investigative techniques ; Polymerase Chain Reaction ; Prognosis ; Reference Values ; Regular ; RNA, Neoplasm - genetics ; RNA, Neoplasm - isolation & purification ; Survival Analysis ; Survivors ; Tumors</subject><ispartof>The American journal of pathology, 2009-03, Vol.174 (3), p.736-745</ispartof><rights>American Society for Investigative Pathology</rights><rights>2009 American Society for Investigative Pathology</rights><rights>2009 INIST-CNRS</rights><rights>Copyright © American Society for Investigative Pathology 2009</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c667t-e7ad70eb8508bb26dd3be34c567d4244af0f84216e30e42d94b2dacb7a0a40333</citedby><cites>FETCH-LOGICAL-c667t-e7ad70eb8508bb26dd3be34c567d4244af0f84216e30e42d94b2dacb7a0a40333</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/PMC2665736/pdf/$$EPDF$$P50$$Gpubmedcentral$$H</linktopdf><linktohtml>$$Uhttps://dx.doi.org/10.2353/ajpath.2009.080731$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>230,314,723,776,780,881,3536,27903,27904,45974,53770,53772</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=21189382$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/19179615$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Childs, Geoffrey</creatorcontrib><creatorcontrib>Fazzari, Melissa</creatorcontrib><creatorcontrib>Kung, Gloria</creatorcontrib><creatorcontrib>Kawachi, Nicole</creatorcontrib><creatorcontrib>Brandwein-Gensler, Margaret</creatorcontrib><creatorcontrib>McLemore, Michael</creatorcontrib><creatorcontrib>Chen, Quan</creatorcontrib><creatorcontrib>Burk, Robert D</creatorcontrib><creatorcontrib>Smith, Richard V</creatorcontrib><creatorcontrib>Prystowsky, Michael B</creatorcontrib><creatorcontrib>Belbin, Thomas J</creatorcontrib><creatorcontrib>Schlecht, Nicolas F</creatorcontrib><title>Low-Level Expression of MicroRNAs let-7d and miR-205 Are Prognostic Markers of Head and Neck Squamous Cell Carcinoma</title><title>The American journal of pathology</title><addtitle>Am J Pathol</addtitle><description>Small noncoding microRNAs (miRNAs) have been shown to be abnormally expressed in every tumor type examined. The importance of miRNAs as potential cancer prognostic indicators is underscored by their involvement in the regulation of basic cellular processes such as cell proliferation, differentiation, and apoptosis. In this study, miRNA expression profiles of head and neck squamous cell carcinoma (HNSCC) tumor and adjacent normal tissue were examined by microarray analysis and validated by quantitative TaqMan real-time polymerase chain reaction. Using TaqMan real-time polymerase chain reaction we measured the quantitative associations between a subset of miRNAs identified on microarrays in primary tumors at diagnosis and cancer survival in a cohort of 104 HNSCC patients undergoing treatment with curative intent. The majority of miRNAs exhibiting altered expression in primary human HNSCC tumors (including miR-1 , miR-133a , miR-205 , and let-7d ) show lower expression levels relative to normal adjacent tissue. In contrast, hsa-miR-21 is frequently overexpressed in human HNSCC tumors. Using univariate and multivariable statistical models we show that low levels of hsa-miR205 are significantly associated with loco-regional recurrence independent of disease severity at diagnosis and treatment. In addition, combined low levels of hsa-miR-205 and hsa-let-7d expression in HNSCC tumors are significantly associated with poor head and neck cancer survival Our results show that miRNA expression levels can be used as prognostic markers of head and neck cancer.</description><subject>Biological and medical sciences</subject><subject>Carcinoma, Squamous Cell - genetics</subject><subject>Carcinoma, Squamous Cell - mortality</subject><subject>Carcinoma, Squamous Cell - pathology</subject><subject>Female</subject><subject>Gene Expression Regulation, Neoplastic</subject><subject>Head and Neck Neoplasms - genetics</subject><subject>Head and Neck Neoplasms - mortality</subject><subject>Head and Neck Neoplasms - pathology</subject><subject>Humans</subject><subject>Investigative techniques, diagnostic techniques (general aspects)</subject><subject>Male</subject><subject>Medical sciences</subject><subject>MicroRNAs - genetics</subject><subject>MicroRNAs - isolation & purification</subject><subject>Middle Aged</subject><subject>Neoplasm Staging</subject><subject>Otorhinolaryngology (head neck, general aspects and miscellaneous)</subject><subject>Otorhinolaryngology. Stomatology</subject><subject>Pathology</subject><subject>Pathology. Cytology. Biochemistry. Spectrometry. Miscellaneous investigative techniques</subject><subject>Polymerase Chain Reaction</subject><subject>Prognosis</subject><subject>Reference Values</subject><subject>Regular</subject><subject>RNA, Neoplasm - genetics</subject><subject>RNA, Neoplasm - isolation & purification</subject><subject>Survival Analysis</subject><subject>Survivors</subject><subject>Tumors</subject><issn>0002-9440</issn><issn>1525-2191</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2009</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kl9v0zAUxSMEYmXwBXhAfgGeUvwvdiKhSVU1GFI30AbPluPctG6TuLOTjn17HKXagIc9WZZ_5_rce26SvCV4TlnGPuntXvebOcW4mOMcS0aeJTOS0SylpCDPkxnGmKYF5_gkeRXCNl4Fy_HL5CQ-y0KQbJb0K3eXruAADTr_vfcQgnUdcjW6tMa766tFQA30qayQ7irU2uuU4gwtPKAf3q07F3pr0KX2O_BhlF2AntArMDt0czvo1g0BLaFp0FJ7YzvX6tfJi1o3Ad4cz9Pk15fzn8uLdPX967flYpUaIWSfgtSVxFDmGc7LkoqqYiUwbjIhK0451zWuc06JAIaB06rgJa20KaXGmmPG2GlyNtXdD2ULlYGu97pRe29b7e-V01b9-9LZjVq7g6JCZJKJWODjsYB3twOEXrU2mNiL7iC2pSQXGHNKZSQ_PEkKUfAsjj2CdALjeEPwUD_YIViNsaopVjXGqqZYo-jd3408So45RuD9EdDB6Kb2ujM2PHCUkLxgOX20ubHrzZ31oEKrmyaWJeO_RHLF1NT55wmEmM_BglfBWOgMVFFkelU5-7Ths__kprGdjdZ2cA9h6wbfxeQVUYEqrG7GTR0XlWCBC5ZR9gcV3-JO</recordid><startdate>20090301</startdate><enddate>20090301</enddate><creator>Childs, Geoffrey</creator><creator>Fazzari, Melissa</creator><creator>Kung, Gloria</creator><creator>Kawachi, Nicole</creator><creator>Brandwein-Gensler, Margaret</creator><creator>McLemore, Michael</creator><creator>Chen, Quan</creator><creator>Burk, Robert D</creator><creator>Smith, Richard V</creator><creator>Prystowsky, Michael B</creator><creator>Belbin, Thomas J</creator><creator>Schlecht, Nicolas F</creator><general>Elsevier Inc</general><general>ASIP</general><general>American Society for Investigative Pathology</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>7TM</scope><scope>5PM</scope></search><sort><creationdate>20090301</creationdate><title>Low-Level Expression of MicroRNAs let-7d and miR-205 Are Prognostic Markers of Head and Neck Squamous Cell Carcinoma</title><author>Childs, Geoffrey ; Fazzari, Melissa ; Kung, Gloria ; Kawachi, Nicole ; Brandwein-Gensler, Margaret ; McLemore, Michael ; Chen, Quan ; Burk, Robert D ; Smith, Richard V ; Prystowsky, Michael B ; Belbin, Thomas J ; Schlecht, Nicolas F</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c667t-e7ad70eb8508bb26dd3be34c567d4244af0f84216e30e42d94b2dacb7a0a40333</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2009</creationdate><topic>Biological and medical sciences</topic><topic>Carcinoma, Squamous Cell - genetics</topic><topic>Carcinoma, Squamous Cell - mortality</topic><topic>Carcinoma, Squamous Cell - pathology</topic><topic>Female</topic><topic>Gene Expression Regulation, Neoplastic</topic><topic>Head and Neck Neoplasms - genetics</topic><topic>Head and Neck Neoplasms - mortality</topic><topic>Head and Neck Neoplasms - pathology</topic><topic>Humans</topic><topic>Investigative techniques, diagnostic techniques (general aspects)</topic><topic>Male</topic><topic>Medical sciences</topic><topic>MicroRNAs - genetics</topic><topic>MicroRNAs - isolation & purification</topic><topic>Middle Aged</topic><topic>Neoplasm Staging</topic><topic>Otorhinolaryngology (head neck, general aspects and miscellaneous)</topic><topic>Otorhinolaryngology. Stomatology</topic><topic>Pathology</topic><topic>Pathology. Cytology. Biochemistry. Spectrometry. Miscellaneous investigative techniques</topic><topic>Polymerase Chain Reaction</topic><topic>Prognosis</topic><topic>Reference Values</topic><topic>Regular</topic><topic>RNA, Neoplasm - genetics</topic><topic>RNA, Neoplasm - isolation & purification</topic><topic>Survival Analysis</topic><topic>Survivors</topic><topic>Tumors</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Childs, Geoffrey</creatorcontrib><creatorcontrib>Fazzari, Melissa</creatorcontrib><creatorcontrib>Kung, Gloria</creatorcontrib><creatorcontrib>Kawachi, Nicole</creatorcontrib><creatorcontrib>Brandwein-Gensler, Margaret</creatorcontrib><creatorcontrib>McLemore, Michael</creatorcontrib><creatorcontrib>Chen, Quan</creatorcontrib><creatorcontrib>Burk, Robert D</creatorcontrib><creatorcontrib>Smith, Richard V</creatorcontrib><creatorcontrib>Prystowsky, Michael B</creatorcontrib><creatorcontrib>Belbin, Thomas J</creatorcontrib><creatorcontrib>Schlecht, Nicolas F</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>Nucleic Acids Abstracts</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>The American journal of pathology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Childs, Geoffrey</au><au>Fazzari, Melissa</au><au>Kung, Gloria</au><au>Kawachi, Nicole</au><au>Brandwein-Gensler, Margaret</au><au>McLemore, Michael</au><au>Chen, Quan</au><au>Burk, Robert D</au><au>Smith, Richard V</au><au>Prystowsky, Michael B</au><au>Belbin, Thomas J</au><au>Schlecht, Nicolas F</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Low-Level Expression of MicroRNAs let-7d and miR-205 Are Prognostic Markers of Head and Neck Squamous Cell Carcinoma</atitle><jtitle>The American journal of pathology</jtitle><addtitle>Am J Pathol</addtitle><date>2009-03-01</date><risdate>2009</risdate><volume>174</volume><issue>3</issue><spage>736</spage><epage>745</epage><pages>736-745</pages><issn>0002-9440</issn><eissn>1525-2191</eissn><coden>AJPAA4</coden><abstract>Small noncoding microRNAs (miRNAs) have been shown to be abnormally expressed in every tumor type examined. The importance of miRNAs as potential cancer prognostic indicators is underscored by their involvement in the regulation of basic cellular processes such as cell proliferation, differentiation, and apoptosis. In this study, miRNA expression profiles of head and neck squamous cell carcinoma (HNSCC) tumor and adjacent normal tissue were examined by microarray analysis and validated by quantitative TaqMan real-time polymerase chain reaction. Using TaqMan real-time polymerase chain reaction we measured the quantitative associations between a subset of miRNAs identified on microarrays in primary tumors at diagnosis and cancer survival in a cohort of 104 HNSCC patients undergoing treatment with curative intent. The majority of miRNAs exhibiting altered expression in primary human HNSCC tumors (including miR-1 , miR-133a , miR-205 , and let-7d ) show lower expression levels relative to normal adjacent tissue. In contrast, hsa-miR-21 is frequently overexpressed in human HNSCC tumors. Using univariate and multivariable statistical models we show that low levels of hsa-miR205 are significantly associated with loco-regional recurrence independent of disease severity at diagnosis and treatment. In addition, combined low levels of hsa-miR-205 and hsa-let-7d expression in HNSCC tumors are significantly associated with poor head and neck cancer survival Our results show that miRNA expression levels can be used as prognostic markers of head and neck cancer.</abstract><cop>Bethesda, MD</cop><pub>Elsevier Inc</pub><pmid>19179615</pmid><doi>10.2353/ajpath.2009.080731</doi><tpages>10</tpages><oa>free_for_read</oa></addata></record> |
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subjects | Biological and medical sciences Carcinoma, Squamous Cell - genetics Carcinoma, Squamous Cell - mortality Carcinoma, Squamous Cell - pathology Female Gene Expression Regulation, Neoplastic Head and Neck Neoplasms - genetics Head and Neck Neoplasms - mortality Head and Neck Neoplasms - pathology Humans Investigative techniques, diagnostic techniques (general aspects) Male Medical sciences MicroRNAs - genetics MicroRNAs - isolation & purification Middle Aged Neoplasm Staging Otorhinolaryngology (head neck, general aspects and miscellaneous) Otorhinolaryngology. Stomatology Pathology Pathology. Cytology. Biochemistry. Spectrometry. Miscellaneous investigative techniques Polymerase Chain Reaction Prognosis Reference Values Regular RNA, Neoplasm - genetics RNA, Neoplasm - isolation & purification Survival Analysis Survivors Tumors |
title | Low-Level Expression of MicroRNAs let-7d and miR-205 Are Prognostic Markers of Head and Neck Squamous Cell Carcinoma |
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