Methylation of the promoter of human leukocyte antigen class I in human esophageal squamous cell carcinoma and its histopathological characteristics

Objective The downregulation of human leukocyte antigen class I (HLA-I) has been proposed to contribute to the immune evasion of cancer cells in some cancers. Meanwhile, transcriptional silencing by means of promoter methylation is now believed to be an important mechanism of carcinogenesis. The aim...

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Veröffentlicht in:The Journal of thoracic and cardiovascular surgery 2011-03, Vol.141 (3), p.808-814
Hauptverfasser: Qifeng, Sun, MD, Bo, Cong, MD, Xingtao, Jiang, MD, Chuanliang, Peng, MD, Xiaogang, Zhao, MD
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container_issue 3
container_start_page 808
container_title The Journal of thoracic and cardiovascular surgery
container_volume 141
creator Qifeng, Sun, MD
Bo, Cong, MD
Xingtao, Jiang, MD
Chuanliang, Peng, MD
Xiaogang, Zhao, MD
description Objective The downregulation of human leukocyte antigen class I (HLA-I) has been proposed to contribute to the immune evasion of cancer cells in some cancers. Meanwhile, transcriptional silencing by means of promoter methylation is now believed to be an important mechanism of carcinogenesis. The aim of this study was (1) to examine the expression of HLA-I antigen and the antigen-processing machinery components in patients with esophageal squamous cell carcinoma lesions and (2) to detect the methylation pattern of the HLA-I gene in patients with esophageal squamous cell carcinoma and assess its association with histopathological characteristics. Methods A total of 87 formalin-fixed and paraffin-embedded esophageal squamous cell carcinoma lesions were collected. HLA-I and antigen-processing machinery component expression was investigated by means of immunohistochemistry with anti–HLA-I monoclonal antibody, and methylation changes in the promoter region of HLA-1 genes were determined by using methylation-specific polymerase chain reaction. Results HLA-I, transporter associated with antigen processing 1, and low molecular weight protein were lost or downregulated in 67%, 29.8%, and 47.0% of the esophageal squamous cell carcinoma lesions, respectively. The positive rates of gene promoter hypermethylation of HLA-I was 70.1% (61/87) in tumor tissues compared with 3.6% in normal tissue ( P  
doi_str_mv 10.1016/j.jtcvs.2010.04.031
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Meanwhile, transcriptional silencing by means of promoter methylation is now believed to be an important mechanism of carcinogenesis. The aim of this study was (1) to examine the expression of HLA-I antigen and the antigen-processing machinery components in patients with esophageal squamous cell carcinoma lesions and (2) to detect the methylation pattern of the HLA-I gene in patients with esophageal squamous cell carcinoma and assess its association with histopathological characteristics. Methods A total of 87 formalin-fixed and paraffin-embedded esophageal squamous cell carcinoma lesions were collected. HLA-I and antigen-processing machinery component expression was investigated by means of immunohistochemistry with anti–HLA-I monoclonal antibody, and methylation changes in the promoter region of HLA-1 genes were determined by using methylation-specific polymerase chain reaction. Results HLA-I, transporter associated with antigen processing 1, and low molecular weight protein were lost or downregulated in 67%, 29.8%, and 47.0% of the esophageal squamous cell carcinoma lesions, respectively. The positive rates of gene promoter hypermethylation of HLA-I was 70.1% (61/87) in tumor tissues compared with 3.6% in normal tissue ( P  &lt; .01). Also, the higher methylation rates and the HLA-I expression were significantly associated with tumor grade, including lymph node metastasis ( P  &lt; .05). Conclusions HLA-I promoter hypermethylation was associated with loss of HLA-I antigen, which frequently occurred in primary tumors, especially in metastatic lymph node lesions, and was associated with patients' prognoses.</description><identifier>ISSN: 0022-5223</identifier><identifier>EISSN: 1097-685X</identifier><identifier>DOI: 10.1016/j.jtcvs.2010.04.031</identifier><identifier>PMID: 21335133</identifier><identifier>CODEN: JTCSAQ</identifier><language>eng</language><publisher>New York, NY: Mosby, Inc</publisher><subject>Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy ; Antigen processing ; ATP-Binding Cassette Sub-Family B Member 2 ; ATP-Binding Cassette Transporters - analysis ; Biological and medical sciences ; Carcinoma, Squamous Cell - genetics ; Carcinoma, Squamous Cell - immunology ; Carcinoma, Squamous Cell - mortality ; Carcinoma, Squamous Cell - pathology ; Cardiology. Vascular system ; Cardiothoracic Surgery ; Chi-Square Distribution ; China ; CpG Islands ; Cysteine Endopeptidases - analysis ; DNA Methylation ; Down-Regulation ; Esophageal Neoplasms - genetics ; Esophageal Neoplasms - immunology ; Esophageal Neoplasms - mortality ; Esophageal Neoplasms - pathology ; Esophagus ; Female ; Gastroenterology. Liver. Pancreas. Abdomen ; Genotype ; Histocompatibility Antigens Class I - analysis ; Histocompatibility Antigens Class I - genetics ; Humans ; Immunohistochemistry ; Lymphatic Metastasis ; Major Histocompatibility Complex ; Male ; Medical sciences ; Middle Aged ; Neoplasm Staging ; Phenotype ; Pneumology ; Polymerase Chain Reaction ; Prognosis ; Promoter Regions, Genetic ; Proportional Hazards Models ; Survival Analysis ; Time Factors ; Tumors</subject><ispartof>The Journal of thoracic and cardiovascular surgery, 2011-03, Vol.141 (3), p.808-814</ispartof><rights>2011</rights><rights>2015 INIST-CNRS</rights><rights>Copyright © 2011. 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Meanwhile, transcriptional silencing by means of promoter methylation is now believed to be an important mechanism of carcinogenesis. The aim of this study was (1) to examine the expression of HLA-I antigen and the antigen-processing machinery components in patients with esophageal squamous cell carcinoma lesions and (2) to detect the methylation pattern of the HLA-I gene in patients with esophageal squamous cell carcinoma and assess its association with histopathological characteristics. Methods A total of 87 formalin-fixed and paraffin-embedded esophageal squamous cell carcinoma lesions were collected. HLA-I and antigen-processing machinery component expression was investigated by means of immunohistochemistry with anti–HLA-I monoclonal antibody, and methylation changes in the promoter region of HLA-1 genes were determined by using methylation-specific polymerase chain reaction. Results HLA-I, transporter associated with antigen processing 1, and low molecular weight protein were lost or downregulated in 67%, 29.8%, and 47.0% of the esophageal squamous cell carcinoma lesions, respectively. The positive rates of gene promoter hypermethylation of HLA-I was 70.1% (61/87) in tumor tissues compared with 3.6% in normal tissue ( P  &lt; .01). Also, the higher methylation rates and the HLA-I expression were significantly associated with tumor grade, including lymph node metastasis ( P  &lt; .05). Conclusions HLA-I promoter hypermethylation was associated with loss of HLA-I antigen, which frequently occurred in primary tumors, especially in metastatic lymph node lesions, and was associated with patients' prognoses.</description><subject>Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy</subject><subject>Antigen processing</subject><subject>ATP-Binding Cassette Sub-Family B Member 2</subject><subject>ATP-Binding Cassette Transporters - analysis</subject><subject>Biological and medical sciences</subject><subject>Carcinoma, Squamous Cell - genetics</subject><subject>Carcinoma, Squamous Cell - immunology</subject><subject>Carcinoma, Squamous Cell - mortality</subject><subject>Carcinoma, Squamous Cell - pathology</subject><subject>Cardiology. Vascular system</subject><subject>Cardiothoracic Surgery</subject><subject>Chi-Square Distribution</subject><subject>China</subject><subject>CpG Islands</subject><subject>Cysteine Endopeptidases - analysis</subject><subject>DNA Methylation</subject><subject>Down-Regulation</subject><subject>Esophageal Neoplasms - genetics</subject><subject>Esophageal Neoplasms - immunology</subject><subject>Esophageal Neoplasms - mortality</subject><subject>Esophageal Neoplasms - pathology</subject><subject>Esophagus</subject><subject>Female</subject><subject>Gastroenterology. Liver. Pancreas. Abdomen</subject><subject>Genotype</subject><subject>Histocompatibility Antigens Class I - analysis</subject><subject>Histocompatibility Antigens Class I - genetics</subject><subject>Humans</subject><subject>Immunohistochemistry</subject><subject>Lymphatic Metastasis</subject><subject>Major Histocompatibility Complex</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Middle Aged</subject><subject>Neoplasm Staging</subject><subject>Phenotype</subject><subject>Pneumology</subject><subject>Polymerase Chain Reaction</subject><subject>Prognosis</subject><subject>Promoter Regions, Genetic</subject><subject>Proportional Hazards Models</subject><subject>Survival Analysis</subject><subject>Time Factors</subject><subject>Tumors</subject><issn>0022-5223</issn><issn>1097-685X</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2011</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFks2KFDEUhQtRnJ7RJxAkG8FNtzdJ_S4UZHB0YMSFCrMLqdStrvRUJT25qYF-Dx_YlN0quHERQpLvJDfn3Cx7wWHDgZdvdptdNA-0EZB2IN-A5I-yFYemWpd1cfs4WwEIsS6EkGfZOdEOACrgzdPsTHApizRW2Y_PGIfDqKP1jvmexQHZPvjJRwzLepgn7diI8503h4hMu2i36JgZNRG7ZtadECS_H_QW9cjoftaTn4kZHEdmdDDW-UknbcdsJDZYin6v4-BHv7UmKcyggzbpyXRiDT3LnvR6JHx-mi-y71cfvl1-Wt98-Xh9-f5mbQrB49p0Uuei0mVTGS6gyhtZlVBj2cu6bTrouchb2dQtlF0DfafbHCpRIzdlW3ag5UX2-nhv-vH9jBTVZGkpWjtM9Suel7UsoMirhMojaoInCtirfbCTDgfFQS1xqJ36FYda4lCQqxRHUr08PTC3E3Z_NL_9T8CrE6ApGdEH7Yylv5xseMVLkbi3Rw6THQ8WgyJj0RnsbEATVeftfwp594_ejNYt3t_hAWnn5-CS04orEgrU16VzlsbhqWdyWd3Kn15mwaE</recordid><startdate>20110301</startdate><enddate>20110301</enddate><creator>Qifeng, Sun, MD</creator><creator>Bo, Cong, MD</creator><creator>Xingtao, Jiang, MD</creator><creator>Chuanliang, Peng, MD</creator><creator>Xiaogang, Zhao, MD</creator><general>Mosby, Inc</general><general>Elsevier</general><scope>6I.</scope><scope>AAFTH</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>7TM</scope></search><sort><creationdate>20110301</creationdate><title>Methylation of the promoter of human leukocyte antigen class I in human esophageal squamous cell carcinoma and its histopathological characteristics</title><author>Qifeng, Sun, MD ; Bo, Cong, MD ; Xingtao, Jiang, MD ; Chuanliang, Peng, MD ; Xiaogang, Zhao, MD</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c521t-cd3a427a697c12074937608e6f38b9d0f124b398b06d90fdab40728e1c6b6d0a3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2011</creationdate><topic>Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy</topic><topic>Antigen processing</topic><topic>ATP-Binding Cassette Sub-Family B Member 2</topic><topic>ATP-Binding Cassette Transporters - analysis</topic><topic>Biological and medical sciences</topic><topic>Carcinoma, Squamous Cell - genetics</topic><topic>Carcinoma, Squamous Cell - immunology</topic><topic>Carcinoma, Squamous Cell - mortality</topic><topic>Carcinoma, Squamous Cell - pathology</topic><topic>Cardiology. Vascular system</topic><topic>Cardiothoracic Surgery</topic><topic>Chi-Square Distribution</topic><topic>China</topic><topic>CpG Islands</topic><topic>Cysteine Endopeptidases - analysis</topic><topic>DNA Methylation</topic><topic>Down-Regulation</topic><topic>Esophageal Neoplasms - genetics</topic><topic>Esophageal Neoplasms - immunology</topic><topic>Esophageal Neoplasms - mortality</topic><topic>Esophageal Neoplasms - pathology</topic><topic>Esophagus</topic><topic>Female</topic><topic>Gastroenterology. Liver. Pancreas. Abdomen</topic><topic>Genotype</topic><topic>Histocompatibility Antigens Class I - analysis</topic><topic>Histocompatibility Antigens Class I - genetics</topic><topic>Humans</topic><topic>Immunohistochemistry</topic><topic>Lymphatic Metastasis</topic><topic>Major Histocompatibility Complex</topic><topic>Male</topic><topic>Medical sciences</topic><topic>Middle Aged</topic><topic>Neoplasm Staging</topic><topic>Phenotype</topic><topic>Pneumology</topic><topic>Polymerase Chain Reaction</topic><topic>Prognosis</topic><topic>Promoter Regions, Genetic</topic><topic>Proportional Hazards Models</topic><topic>Survival Analysis</topic><topic>Time Factors</topic><topic>Tumors</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Qifeng, Sun, MD</creatorcontrib><creatorcontrib>Bo, Cong, MD</creatorcontrib><creatorcontrib>Xingtao, Jiang, MD</creatorcontrib><creatorcontrib>Chuanliang, Peng, MD</creatorcontrib><creatorcontrib>Xiaogang, Zhao, MD</creatorcontrib><collection>ScienceDirect Open Access Titles</collection><collection>Elsevier:ScienceDirect:Open Access</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>Nucleic Acids Abstracts</collection><jtitle>The Journal of thoracic and cardiovascular surgery</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Qifeng, Sun, MD</au><au>Bo, Cong, MD</au><au>Xingtao, Jiang, MD</au><au>Chuanliang, Peng, MD</au><au>Xiaogang, Zhao, MD</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Methylation of the promoter of human leukocyte antigen class I in human esophageal squamous cell carcinoma and its histopathological characteristics</atitle><jtitle>The Journal of thoracic and cardiovascular surgery</jtitle><addtitle>J Thorac Cardiovasc Surg</addtitle><date>2011-03-01</date><risdate>2011</risdate><volume>141</volume><issue>3</issue><spage>808</spage><epage>814</epage><pages>808-814</pages><issn>0022-5223</issn><eissn>1097-685X</eissn><coden>JTCSAQ</coden><abstract>Objective The downregulation of human leukocyte antigen class I (HLA-I) has been proposed to contribute to the immune evasion of cancer cells in some cancers. Meanwhile, transcriptional silencing by means of promoter methylation is now believed to be an important mechanism of carcinogenesis. The aim of this study was (1) to examine the expression of HLA-I antigen and the antigen-processing machinery components in patients with esophageal squamous cell carcinoma lesions and (2) to detect the methylation pattern of the HLA-I gene in patients with esophageal squamous cell carcinoma and assess its association with histopathological characteristics. Methods A total of 87 formalin-fixed and paraffin-embedded esophageal squamous cell carcinoma lesions were collected. HLA-I and antigen-processing machinery component expression was investigated by means of immunohistochemistry with anti–HLA-I monoclonal antibody, and methylation changes in the promoter region of HLA-1 genes were determined by using methylation-specific polymerase chain reaction. Results HLA-I, transporter associated with antigen processing 1, and low molecular weight protein were lost or downregulated in 67%, 29.8%, and 47.0% of the esophageal squamous cell carcinoma lesions, respectively. The positive rates of gene promoter hypermethylation of HLA-I was 70.1% (61/87) in tumor tissues compared with 3.6% in normal tissue ( P  &lt; .01). Also, the higher methylation rates and the HLA-I expression were significantly associated with tumor grade, including lymph node metastasis ( P  &lt; .05). Conclusions HLA-I promoter hypermethylation was associated with loss of HLA-I antigen, which frequently occurred in primary tumors, especially in metastatic lymph node lesions, and was associated with patients' prognoses.</abstract><cop>New York, NY</cop><pub>Mosby, Inc</pub><pmid>21335133</pmid><doi>10.1016/j.jtcvs.2010.04.031</doi><tpages>7</tpages><oa>free_for_read</oa></addata></record>
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subjects Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy
Antigen processing
ATP-Binding Cassette Sub-Family B Member 2
ATP-Binding Cassette Transporters - analysis
Biological and medical sciences
Carcinoma, Squamous Cell - genetics
Carcinoma, Squamous Cell - immunology
Carcinoma, Squamous Cell - mortality
Carcinoma, Squamous Cell - pathology
Cardiology. Vascular system
Cardiothoracic Surgery
Chi-Square Distribution
China
CpG Islands
Cysteine Endopeptidases - analysis
DNA Methylation
Down-Regulation
Esophageal Neoplasms - genetics
Esophageal Neoplasms - immunology
Esophageal Neoplasms - mortality
Esophageal Neoplasms - pathology
Esophagus
Female
Gastroenterology. Liver. Pancreas. Abdomen
Genotype
Histocompatibility Antigens Class I - analysis
Histocompatibility Antigens Class I - genetics
Humans
Immunohistochemistry
Lymphatic Metastasis
Major Histocompatibility Complex
Male
Medical sciences
Middle Aged
Neoplasm Staging
Phenotype
Pneumology
Polymerase Chain Reaction
Prognosis
Promoter Regions, Genetic
Proportional Hazards Models
Survival Analysis
Time Factors
Tumors
title Methylation of the promoter of human leukocyte antigen class I in human esophageal squamous cell carcinoma and its histopathological characteristics
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