Promoter DNA Methylation and mRNA Expression Level of p16 Gene in Oral Squamous Cell Carcinoma: Correlation with Clinicopathological Characteristics
The aim of this study was to investigate the relationship between p16 methylation and its expression in oral squamous cell carcinoma (OSCC). Also the contribution of clinicopathological factors, HPV infection and smoking in p16 expression and promoter methylation has been investigated. In this study...
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| Veröffentlicht in: | Pathology oncology research 2019-10, Vol.25 (4), p.1535-1543 |
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| creator | Allameh, Abdolamir Moazeni-Roodi, Abdolkarim Harirchi, Iraj Ravanshad, Mehrdad Motiee-Langroudi, Maziar Garajei, Ata Hamidavi, Azin Mesbah-Namin, Seyed Alireza |
| description | The aim of this study was to investigate the relationship between p16 methylation and its expression in oral squamous cell carcinoma (OSCC). Also the contribution of clinicopathological factors, HPV infection and smoking in p16 expression and promoter methylation has been investigated. In this study 67 consecutive OSCC patients and 59 normal individuals were enrolled. All patients were candidates for surgery of oral cavity and fresh tumor biopsies were collected and processed for DNA and RNA extraction. Normal gingival tissues were collected from individuals referred to dentistry clinic and considered as controls. All the cases and controls were checked for HPV infection and then promoter methylation and expression of p16 gene were determined using Methylation-specific PCR (MSP) and real-time PCR (QPCR), respectively. Methylation of p16 in tumors and normal tissues were 59.7 and 38.9%, respectively. Most of hypermethylated samples (>82%) were in high grades. P16 methylation was comparable in HPV+ and HPV- patients or smokers. P16 was overexpressed (~3 fold;
p
= 0.044) in HPV+ tumors, but it was significantly down-regulated in smoker patients (40% of all tumors). Comparison of P16 expression in OSCC tumors with different degrees of promoter methylation further suggest the relationship of methylation rate and down-regulation of P16 expression. The p16 methylation and expression was differentially affected in patients with HPV infection and the smoker cases. Regardless of the influence of environmental factors, it appears that P16 status is useful for classifying patients with OSCC and for influencing treatment strategies in accordance with this classification. Moreover, targeting the upregulation of p16 could be a promising therapeutic option. |
| doi_str_mv | 10.1007/s12253-018-0542-1 |
| format | Article |
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p
= 0.044) in HPV+ tumors, but it was significantly down-regulated in smoker patients (40% of all tumors). Comparison of P16 expression in OSCC tumors with different degrees of promoter methylation further suggest the relationship of methylation rate and down-regulation of P16 expression. The p16 methylation and expression was differentially affected in patients with HPV infection and the smoker cases. Regardless of the influence of environmental factors, it appears that P16 status is useful for classifying patients with OSCC and for influencing treatment strategies in accordance with this classification. Moreover, targeting the upregulation of p16 could be a promising therapeutic option.</description><identifier>ISSN: 1219-4956</identifier><identifier>EISSN: 1532-2807</identifier><identifier>DOI: 10.1007/s12253-018-0542-1</identifier><identifier>PMID: 30511108</identifier><language>eng</language><publisher>Dordrecht: Springer Netherlands</publisher><subject>Adult ; Aged ; Biomarkers, Tumor - genetics ; Biomarkers, Tumor - metabolism ; Biomedical and Life Sciences ; Biomedicine ; Cancer Research ; Carcinoma, Squamous Cell - genetics ; Carcinoma, Squamous Cell - metabolism ; Carcinoma, Squamous Cell - pathology ; Carcinoma, Squamous Cell - virology ; Case-Control Studies ; Cyclin-Dependent Kinase Inhibitor p16 - genetics ; Cyclin-Dependent Kinase Inhibitor p16 - metabolism ; Dentistry ; Deoxyribonucleic acid ; DNA ; DNA Methylation ; Environmental factors ; Female ; Follow-Up Studies ; Gene expression ; Gene Expression Regulation, Neoplastic ; Human papillomavirus ; Humans ; Immunology ; Infections ; Male ; Middle Aged ; Mouth Neoplasms - genetics ; Mouth Neoplasms - metabolism ; Mouth Neoplasms - pathology ; Oncology ; Oral cancer ; Oral cavity ; Oral squamous cell carcinoma ; Original Article ; p16 Protein ; Papillomaviridae - isolation & purification ; Papillomavirus Infections - complications ; Papillomavirus Infections - virology ; Pathology ; Patients ; Polymerase chain reaction ; Prognosis ; Promoter Regions, Genetic ; Smoking ; Squamous cell carcinoma ; Surgery ; Tissues ; Tumors</subject><ispartof>Pathology oncology research, 2019-10, Vol.25 (4), p.1535-1543</ispartof><rights>Arányi Lajos Foundation 2018</rights><rights>Pathology & Oncology Research is a copyright of Springer, (2018). All Rights Reserved.</rights><rights>Copyright Springer Nature B.V. 2019</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c400t-7d868cf88a0dd7dc8b2913edfd7ae38f0b896280c1801d38148a9d181ea09a833</citedby><cites>FETCH-LOGICAL-c400t-7d868cf88a0dd7dc8b2913edfd7ae38f0b896280c1801d38148a9d181ea09a833</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1007/s12253-018-0542-1$$EPDF$$P50$$Gspringer$$H</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1007/s12253-018-0542-1$$EHTML$$P50$$Gspringer$$H</linktohtml><link.rule.ids>314,780,784,27924,27925,41488,42557,51319</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/30511108$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Allameh, Abdolamir</creatorcontrib><creatorcontrib>Moazeni-Roodi, Abdolkarim</creatorcontrib><creatorcontrib>Harirchi, Iraj</creatorcontrib><creatorcontrib>Ravanshad, Mehrdad</creatorcontrib><creatorcontrib>Motiee-Langroudi, Maziar</creatorcontrib><creatorcontrib>Garajei, Ata</creatorcontrib><creatorcontrib>Hamidavi, Azin</creatorcontrib><creatorcontrib>Mesbah-Namin, Seyed Alireza</creatorcontrib><title>Promoter DNA Methylation and mRNA Expression Level of p16 Gene in Oral Squamous Cell Carcinoma: Correlation with Clinicopathological Characteristics</title><title>Pathology oncology research</title><addtitle>Pathol. Oncol. Res</addtitle><addtitle>Pathol Oncol Res</addtitle><description>The aim of this study was to investigate the relationship between p16 methylation and its expression in oral squamous cell carcinoma (OSCC). Also the contribution of clinicopathological factors, HPV infection and smoking in p16 expression and promoter methylation has been investigated. In this study 67 consecutive OSCC patients and 59 normal individuals were enrolled. All patients were candidates for surgery of oral cavity and fresh tumor biopsies were collected and processed for DNA and RNA extraction. Normal gingival tissues were collected from individuals referred to dentistry clinic and considered as controls. All the cases and controls were checked for HPV infection and then promoter methylation and expression of p16 gene were determined using Methylation-specific PCR (MSP) and real-time PCR (QPCR), respectively. Methylation of p16 in tumors and normal tissues were 59.7 and 38.9%, respectively. Most of hypermethylated samples (>82%) were in high grades. P16 methylation was comparable in HPV+ and HPV- patients or smokers. P16 was overexpressed (~3 fold;
p
= 0.044) in HPV+ tumors, but it was significantly down-regulated in smoker patients (40% of all tumors). Comparison of P16 expression in OSCC tumors with different degrees of promoter methylation further suggest the relationship of methylation rate and down-regulation of P16 expression. The p16 methylation and expression was differentially affected in patients with HPV infection and the smoker cases. Regardless of the influence of environmental factors, it appears that P16 status is useful for classifying patients with OSCC and for influencing treatment strategies in accordance with this classification. Moreover, targeting the upregulation of p16 could be a promising therapeutic option.</description><subject>Adult</subject><subject>Aged</subject><subject>Biomarkers, Tumor - genetics</subject><subject>Biomarkers, Tumor - metabolism</subject><subject>Biomedical and Life Sciences</subject><subject>Biomedicine</subject><subject>Cancer Research</subject><subject>Carcinoma, Squamous Cell - genetics</subject><subject>Carcinoma, Squamous Cell - metabolism</subject><subject>Carcinoma, Squamous Cell - pathology</subject><subject>Carcinoma, Squamous Cell - virology</subject><subject>Case-Control Studies</subject><subject>Cyclin-Dependent Kinase Inhibitor p16 - genetics</subject><subject>Cyclin-Dependent Kinase Inhibitor p16 - metabolism</subject><subject>Dentistry</subject><subject>Deoxyribonucleic acid</subject><subject>DNA</subject><subject>DNA Methylation</subject><subject>Environmental factors</subject><subject>Female</subject><subject>Follow-Up Studies</subject><subject>Gene expression</subject><subject>Gene Expression Regulation, Neoplastic</subject><subject>Human papillomavirus</subject><subject>Humans</subject><subject>Immunology</subject><subject>Infections</subject><subject>Male</subject><subject>Middle Aged</subject><subject>Mouth Neoplasms - genetics</subject><subject>Mouth Neoplasms - metabolism</subject><subject>Mouth Neoplasms - pathology</subject><subject>Oncology</subject><subject>Oral cancer</subject><subject>Oral cavity</subject><subject>Oral squamous cell carcinoma</subject><subject>Original Article</subject><subject>p16 Protein</subject><subject>Papillomaviridae - isolation & purification</subject><subject>Papillomavirus Infections - complications</subject><subject>Papillomavirus Infections - virology</subject><subject>Pathology</subject><subject>Patients</subject><subject>Polymerase chain reaction</subject><subject>Prognosis</subject><subject>Promoter Regions, Genetic</subject><subject>Smoking</subject><subject>Squamous cell carcinoma</subject><subject>Surgery</subject><subject>Tissues</subject><subject>Tumors</subject><issn>1219-4956</issn><issn>1532-2807</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2019</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><recordid>eNp9kctu1DAUhi0EoqXwAGyQJTZsAufYuTjsqtAWpGmLuKwtj-10XCV2aifQvgcPXI9mAAmprGzZ3_-fy0_IS4S3CNC8S8hYxQtAUUBVsgIfkUOsOCuYgOZxvjNsi7Kt6gPyLKVryJq6rZ-SAw4VIoI4JL8-xzCG2Ub64eKYntt5czeo2QVPlTd0_JIfT26naFPavq3sDzvQ0NMJa3pmvaXO08uoBvr1ZlFjWBLt7DDQTkXtfBjVe9qFGO3e8qebN7QbnHc6TGrehCFcOZ3V3UZFpXMXLs1Op-fkSa-GZF_szyPy_fTkW_exWF2efeqOV4UuAeaiMaIWuhdCgTGN0WLNWuTW9KZRlose1qKt8yo0CkDDBZZCtQYFWgWtEpwfkTc73ymGm8WmWY4u6TyA8jbPIhmWrajLvMGMvv4HvQ5L9Lk7yTjkOgLE_6lcvWQIFcsU7igdQ0rR9nKKblTxTiLIbbByF6zMwcptsBKz5tXeeVmP1vxR_E4yA2wHpPzlr2z8W_ph13uqHq1X</recordid><startdate>20191001</startdate><enddate>20191001</enddate><creator>Allameh, Abdolamir</creator><creator>Moazeni-Roodi, Abdolkarim</creator><creator>Harirchi, Iraj</creator><creator>Ravanshad, Mehrdad</creator><creator>Motiee-Langroudi, Maziar</creator><creator>Garajei, Ata</creator><creator>Hamidavi, Azin</creator><creator>Mesbah-Namin, Seyed Alireza</creator><general>Springer Netherlands</general><general>Springer Nature B.V</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>7RV</scope><scope>7T5</scope><scope>7TM</scope><scope>7TO</scope><scope>7U9</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>BENPR</scope><scope>CCPQU</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>H94</scope><scope>K9.</scope><scope>KB0</scope><scope>M0S</scope><scope>M1P</scope><scope>M7N</scope><scope>NAPCQ</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>7X8</scope></search><sort><creationdate>20191001</creationdate><title>Promoter DNA Methylation and mRNA Expression Level of p16 Gene in Oral Squamous Cell Carcinoma: Correlation with Clinicopathological Characteristics</title><author>Allameh, Abdolamir ; Moazeni-Roodi, Abdolkarim ; Harirchi, Iraj ; Ravanshad, Mehrdad ; Motiee-Langroudi, Maziar ; Garajei, Ata ; Hamidavi, Azin ; Mesbah-Namin, Seyed Alireza</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c400t-7d868cf88a0dd7dc8b2913edfd7ae38f0b896280c1801d38148a9d181ea09a833</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2019</creationdate><topic>Adult</topic><topic>Aged</topic><topic>Biomarkers, Tumor - genetics</topic><topic>Biomarkers, Tumor - metabolism</topic><topic>Biomedical and Life Sciences</topic><topic>Biomedicine</topic><topic>Cancer Research</topic><topic>Carcinoma, Squamous Cell - genetics</topic><topic>Carcinoma, Squamous Cell - metabolism</topic><topic>Carcinoma, Squamous Cell - pathology</topic><topic>Carcinoma, Squamous Cell - virology</topic><topic>Case-Control Studies</topic><topic>Cyclin-Dependent Kinase Inhibitor p16 - genetics</topic><topic>Cyclin-Dependent Kinase Inhibitor p16 - metabolism</topic><topic>Dentistry</topic><topic>Deoxyribonucleic acid</topic><topic>DNA</topic><topic>DNA Methylation</topic><topic>Environmental factors</topic><topic>Female</topic><topic>Follow-Up Studies</topic><topic>Gene expression</topic><topic>Gene Expression Regulation, Neoplastic</topic><topic>Human papillomavirus</topic><topic>Humans</topic><topic>Immunology</topic><topic>Infections</topic><topic>Male</topic><topic>Middle Aged</topic><topic>Mouth Neoplasms - genetics</topic><topic>Mouth Neoplasms - metabolism</topic><topic>Mouth Neoplasms - pathology</topic><topic>Oncology</topic><topic>Oral cancer</topic><topic>Oral cavity</topic><topic>Oral squamous cell carcinoma</topic><topic>Original Article</topic><topic>p16 Protein</topic><topic>Papillomaviridae - isolation & purification</topic><topic>Papillomavirus Infections - complications</topic><topic>Papillomavirus Infections - virology</topic><topic>Pathology</topic><topic>Patients</topic><topic>Polymerase chain reaction</topic><topic>Prognosis</topic><topic>Promoter Regions, Genetic</topic><topic>Smoking</topic><topic>Squamous cell carcinoma</topic><topic>Surgery</topic><topic>Tissues</topic><topic>Tumors</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Allameh, Abdolamir</creatorcontrib><creatorcontrib>Moazeni-Roodi, Abdolkarim</creatorcontrib><creatorcontrib>Harirchi, Iraj</creatorcontrib><creatorcontrib>Ravanshad, Mehrdad</creatorcontrib><creatorcontrib>Motiee-Langroudi, Maziar</creatorcontrib><creatorcontrib>Garajei, Ata</creatorcontrib><creatorcontrib>Hamidavi, Azin</creatorcontrib><creatorcontrib>Mesbah-Namin, Seyed Alireza</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>Nursing & Allied Health Database</collection><collection>Immunology Abstracts</collection><collection>Nucleic Acids Abstracts</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>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</collection><collection>ProQuest One Community College</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Nursing & Allied Health Database (Alumni Edition)</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</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>MEDLINE - Academic</collection><jtitle>Pathology oncology research</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Allameh, Abdolamir</au><au>Moazeni-Roodi, Abdolkarim</au><au>Harirchi, Iraj</au><au>Ravanshad, Mehrdad</au><au>Motiee-Langroudi, Maziar</au><au>Garajei, Ata</au><au>Hamidavi, Azin</au><au>Mesbah-Namin, Seyed Alireza</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Promoter DNA Methylation and mRNA Expression Level of p16 Gene in Oral Squamous Cell Carcinoma: Correlation with Clinicopathological Characteristics</atitle><jtitle>Pathology oncology research</jtitle><stitle>Pathol. Oncol. Res</stitle><addtitle>Pathol Oncol Res</addtitle><date>2019-10-01</date><risdate>2019</risdate><volume>25</volume><issue>4</issue><spage>1535</spage><epage>1543</epage><pages>1535-1543</pages><issn>1219-4956</issn><eissn>1532-2807</eissn><abstract>The aim of this study was to investigate the relationship between p16 methylation and its expression in oral squamous cell carcinoma (OSCC). Also the contribution of clinicopathological factors, HPV infection and smoking in p16 expression and promoter methylation has been investigated. In this study 67 consecutive OSCC patients and 59 normal individuals were enrolled. All patients were candidates for surgery of oral cavity and fresh tumor biopsies were collected and processed for DNA and RNA extraction. Normal gingival tissues were collected from individuals referred to dentistry clinic and considered as controls. All the cases and controls were checked for HPV infection and then promoter methylation and expression of p16 gene were determined using Methylation-specific PCR (MSP) and real-time PCR (QPCR), respectively. Methylation of p16 in tumors and normal tissues were 59.7 and 38.9%, respectively. Most of hypermethylated samples (>82%) were in high grades. P16 methylation was comparable in HPV+ and HPV- patients or smokers. P16 was overexpressed (~3 fold;
p
= 0.044) in HPV+ tumors, but it was significantly down-regulated in smoker patients (40% of all tumors). Comparison of P16 expression in OSCC tumors with different degrees of promoter methylation further suggest the relationship of methylation rate and down-regulation of P16 expression. The p16 methylation and expression was differentially affected in patients with HPV infection and the smoker cases. Regardless of the influence of environmental factors, it appears that P16 status is useful for classifying patients with OSCC and for influencing treatment strategies in accordance with this classification. Moreover, targeting the upregulation of p16 could be a promising therapeutic option.</abstract><cop>Dordrecht</cop><pub>Springer Netherlands</pub><pmid>30511108</pmid><doi>10.1007/s12253-018-0542-1</doi><tpages>9</tpages></addata></record> |
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| ispartof | Pathology oncology research, 2019-10, Vol.25 (4), p.1535-1543 |
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| subjects | Adult Aged Biomarkers, Tumor - genetics Biomarkers, Tumor - metabolism Biomedical and Life Sciences Biomedicine Cancer Research Carcinoma, Squamous Cell - genetics Carcinoma, Squamous Cell - metabolism Carcinoma, Squamous Cell - pathology Carcinoma, Squamous Cell - virology Case-Control Studies Cyclin-Dependent Kinase Inhibitor p16 - genetics Cyclin-Dependent Kinase Inhibitor p16 - metabolism Dentistry Deoxyribonucleic acid DNA DNA Methylation Environmental factors Female Follow-Up Studies Gene expression Gene Expression Regulation, Neoplastic Human papillomavirus Humans Immunology Infections Male Middle Aged Mouth Neoplasms - genetics Mouth Neoplasms - metabolism Mouth Neoplasms - pathology Oncology Oral cancer Oral cavity Oral squamous cell carcinoma Original Article p16 Protein Papillomaviridae - isolation & purification Papillomavirus Infections - complications Papillomavirus Infections - virology Pathology Patients Polymerase chain reaction Prognosis Promoter Regions, Genetic Smoking Squamous cell carcinoma Surgery Tissues Tumors |
| title | Promoter DNA Methylation and mRNA Expression Level of p16 Gene in Oral Squamous Cell Carcinoma: Correlation with Clinicopathological Characteristics |
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