High CpG island methylator phenotype is associated with lymph node metastasis and prognosis in gastric cancer
Several studies have found that the promoter CpG island is frequently methylated in gastric cancer. The CpG island methylator phenotype (CIMP) defines concordant methylation of multiple promoter CpG island loci in a subset of gastric cancer. However, the relationship between CIMP and lymph node meta...
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| Veröffentlicht in: | Cancer science 2012-01, Vol.103 (1), p.73-79 |
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| creator | Chen, Hua‐Yun Zhu, Bao‐He Zhang, Chang‐Hua Yang, Dong‐Jie Peng, Jian‐Jun Chen, Jian‐Hui Liu, Fa‐Keng He, Yu‐Long |
| description | Several studies have found that the promoter CpG island is frequently methylated in gastric cancer. The CpG island methylator phenotype (CIMP) defines concordant methylation of multiple promoter CpG island loci in a subset of gastric cancer. However, the relationship between CIMP and lymph node metastasis in gastric cancer is unknown. Our study aimed to characterize the role of CIMP in lymph node metastasis. Clinical specimens from 120 patients were analyzed and PCR was used to detect the methylation status of five genes (ALX4, TMEFF2, CHCHD10, IGFBP3, and NPR1). We measured the level of mRNA for the five genes by real‐time RT‐PCR. Microsatellite instability and Helicobacter pylori infection status were assayed by capillary electrophoresis and real‐time PCR, respectively. DNA methylation in the five genes was correlated with low expression of the respective mRNA. With CIMP as the dependent variable, CIMP‐high gastric cancer tended to show more distant lymph node metastasis, higher pathologic tumor classification, more pathologic metastasis, and higher pathologic TNM status. Microsatellite instability and H. pylori status were not significant predictors of prognosis. CIMP‐high gastric cancer showed significantly worse survival compared with that of CIMP‐low/CIMP‐negative gastric cancer (P |
| doi_str_mv | 10.1111/j.1349-7006.2011.02129.x |
| format | Article |
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The CpG island methylator phenotype (CIMP) defines concordant methylation of multiple promoter CpG island loci in a subset of gastric cancer. However, the relationship between CIMP and lymph node metastasis in gastric cancer is unknown. Our study aimed to characterize the role of CIMP in lymph node metastasis. Clinical specimens from 120 patients were analyzed and PCR was used to detect the methylation status of five genes (ALX4, TMEFF2, CHCHD10, IGFBP3, and NPR1). We measured the level of mRNA for the five genes by real‐time RT‐PCR. Microsatellite instability and Helicobacter pylori infection status were assayed by capillary electrophoresis and real‐time PCR, respectively. DNA methylation in the five genes was correlated with low expression of the respective mRNA. With CIMP as the dependent variable, CIMP‐high gastric cancer tended to show more distant lymph node metastasis, higher pathologic tumor classification, more pathologic metastasis, and higher pathologic TNM status. Microsatellite instability and H. pylori status were not significant predictors of prognosis. CIMP‐high gastric cancer showed significantly worse survival compared with that of CIMP‐low/CIMP‐negative gastric cancer (P < 0.001). Our results show that there is an association between CIMP status and lymph node metastasis in gastric cancer and CIMP‐high was an independent prognostic factor. (Cancer Sci 2012; 103: 73–79)</description><identifier>ISSN: 1347-9032</identifier><identifier>EISSN: 1349-7006</identifier><identifier>DOI: 10.1111/j.1349-7006.2011.02129.x</identifier><identifier>PMID: 22017425</identifier><language>eng</language><publisher>Oxford, UK: Blackwell Publishing Ltd</publisher><subject>Adult ; Aged ; Aged, 80 and over ; Cancer therapies ; Capillary electrophoresis ; Colorectal cancer ; CpG islands ; CpG Islands - genetics ; DNA Methylation ; DNA-Binding Proteins - genetics ; Female ; Gastric cancer ; Gene expression ; Gene Expression Regulation, Neoplastic ; Genes, Tumor Suppressor ; Genetic testing ; Helicobacter Infections - genetics ; Helicobacter Infections - pathology ; Helicobacter Infections - virology ; Helicobacter pylori ; Helicobacter pylori - genetics ; Humans ; Insulin-Like Growth Factor Binding Protein 3 - genetics ; Insulin-like growth factor-binding protein 3 ; Lymph nodes ; Lymphatic Metastasis ; Male ; Medical prognosis ; Membrane Proteins - genetics ; Metastases ; Microsatellite Instability ; Middle Aged ; Mitochondrial Proteins - genetics ; Mortality ; mRNA ; Neoplasm Proteins - genetics ; Neoplasm Staging ; Original ; Phenotype ; Phenotypes ; Polymerase chain reaction ; Prognosis ; Real-Time Polymerase Chain Reaction ; Receptors, Atrial Natriuretic Factor - genetics ; RNA, Neoplasm ; Stomach Neoplasms - genetics ; Stomach Neoplasms - mortality ; Stomach Neoplasms - pathology ; Stomach Neoplasms - virology ; Survival Rate ; Transcription Factors - genetics ; Tumors</subject><ispartof>Cancer science, 2012-01, Vol.103 (1), p.73-79</ispartof><rights>2011 Japanese Cancer Association</rights><rights>2011 Japanese Cancer Association.</rights><rights>Copyright John Wiley & Sons, Inc. Jan 2012</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c4769-2b7e5e8f538f4fe775e79e03c73a48a68444ea9d640dc7e70c55f437d045e90d3</citedby><cites>FETCH-LOGICAL-c4769-2b7e5e8f538f4fe775e79e03c73a48a68444ea9d640dc7e70c55f437d045e90d3</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/PMC11164149/pdf/$$EPDF$$P50$$Gpubmedcentral$$H</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC11164149/$$EHTML$$P50$$Gpubmedcentral$$H</linktohtml><link.rule.ids>230,315,728,781,785,886,1418,11567,27929,27930,45579,45580,46057,46481,53796,53798</link.rule.ids><linktorsrc>$$Uhttps://onlinelibrary.wiley.com/doi/abs/10.1111%2Fj.1349-7006.2011.02129.x$$EView_record_in_Wiley-Blackwell$$FView_record_in_$$GWiley-Blackwell</linktorsrc><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/22017425$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Chen, Hua‐Yun</creatorcontrib><creatorcontrib>Zhu, Bao‐He</creatorcontrib><creatorcontrib>Zhang, Chang‐Hua</creatorcontrib><creatorcontrib>Yang, Dong‐Jie</creatorcontrib><creatorcontrib>Peng, Jian‐Jun</creatorcontrib><creatorcontrib>Chen, Jian‐Hui</creatorcontrib><creatorcontrib>Liu, Fa‐Keng</creatorcontrib><creatorcontrib>He, Yu‐Long</creatorcontrib><title>High CpG island methylator phenotype is associated with lymph node metastasis and prognosis in gastric cancer</title><title>Cancer science</title><addtitle>Cancer Sci</addtitle><description>Several studies have found that the promoter CpG island is frequently methylated in gastric cancer. The CpG island methylator phenotype (CIMP) defines concordant methylation of multiple promoter CpG island loci in a subset of gastric cancer. However, the relationship between CIMP and lymph node metastasis in gastric cancer is unknown. Our study aimed to characterize the role of CIMP in lymph node metastasis. Clinical specimens from 120 patients were analyzed and PCR was used to detect the methylation status of five genes (ALX4, TMEFF2, CHCHD10, IGFBP3, and NPR1). We measured the level of mRNA for the five genes by real‐time RT‐PCR. Microsatellite instability and Helicobacter pylori infection status were assayed by capillary electrophoresis and real‐time PCR, respectively. DNA methylation in the five genes was correlated with low expression of the respective mRNA. With CIMP as the dependent variable, CIMP‐high gastric cancer tended to show more distant lymph node metastasis, higher pathologic tumor classification, more pathologic metastasis, and higher pathologic TNM status. Microsatellite instability and H. pylori status were not significant predictors of prognosis. CIMP‐high gastric cancer showed significantly worse survival compared with that of CIMP‐low/CIMP‐negative gastric cancer (P < 0.001). Our results show that there is an association between CIMP status and lymph node metastasis in gastric cancer and CIMP‐high was an independent prognostic factor. (Cancer Sci 2012; 103: 73–79)</description><subject>Adult</subject><subject>Aged</subject><subject>Aged, 80 and over</subject><subject>Cancer therapies</subject><subject>Capillary electrophoresis</subject><subject>Colorectal cancer</subject><subject>CpG islands</subject><subject>CpG Islands - genetics</subject><subject>DNA Methylation</subject><subject>DNA-Binding Proteins - genetics</subject><subject>Female</subject><subject>Gastric cancer</subject><subject>Gene expression</subject><subject>Gene Expression Regulation, Neoplastic</subject><subject>Genes, Tumor Suppressor</subject><subject>Genetic testing</subject><subject>Helicobacter Infections - genetics</subject><subject>Helicobacter Infections - pathology</subject><subject>Helicobacter Infections - virology</subject><subject>Helicobacter pylori</subject><subject>Helicobacter pylori - genetics</subject><subject>Humans</subject><subject>Insulin-Like Growth Factor Binding Protein 3 - genetics</subject><subject>Insulin-like growth factor-binding protein 3</subject><subject>Lymph nodes</subject><subject>Lymphatic Metastasis</subject><subject>Male</subject><subject>Medical prognosis</subject><subject>Membrane Proteins - genetics</subject><subject>Metastases</subject><subject>Microsatellite Instability</subject><subject>Middle Aged</subject><subject>Mitochondrial Proteins - genetics</subject><subject>Mortality</subject><subject>mRNA</subject><subject>Neoplasm Proteins - genetics</subject><subject>Neoplasm Staging</subject><subject>Original</subject><subject>Phenotype</subject><subject>Phenotypes</subject><subject>Polymerase chain reaction</subject><subject>Prognosis</subject><subject>Real-Time Polymerase Chain Reaction</subject><subject>Receptors, Atrial Natriuretic Factor - genetics</subject><subject>RNA, Neoplasm</subject><subject>Stomach Neoplasms - genetics</subject><subject>Stomach Neoplasms - mortality</subject><subject>Stomach Neoplasms - pathology</subject><subject>Stomach Neoplasms - virology</subject><subject>Survival Rate</subject><subject>Transcription Factors - genetics</subject><subject>Tumors</subject><issn>1347-9032</issn><issn>1349-7006</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2012</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><recordid>eNqNUd9v1SAUJkbj5vRfMCQ--NQKBUp5MGa50c1kiQ-bz4TR01tuWqjQ69b_Xro7b3RPIyQc8v2Acz6EMCUlzevTrqSMq0ISUpcVobQkFa1Uef8CnR6Blw-1LBRh1Ql6k9KOEFZzxV-jkyqLJK_EKRov3bbHm-kCuzQY3-IR5n4ZzBwinnrwYV4myBg2KQXrzAwtvnNzj4dlnHrsQwurxKS8V1Z2mGLY-rDenMfbjERnsTXeQnyLXnVmSPDu8TxDP799vdlcFlc_Lr5vzq8Ky2WtiupWgoCmE6zpeAdSCpAKCLOSGd6YuuGcg1FtzUlrJUhiheg4ky3hAhRp2Rn6cvCd9rcjtBb8HM2gp-hGExcdjNP_I971eht-6zzcmlOussPHR4cYfu0hzXp0ycKQZwRhn7SivJZUEJ6ZH54wd2EffW5PV0oyXgvJ6sxqDiwbQ0oRuuNnKFlfpXqn1-j0Gp1eM9UPmer7LH3_bzNH4d8QM-HzgXDnBliebaw359drxf4Aj_axkw</recordid><startdate>201201</startdate><enddate>201201</enddate><creator>Chen, Hua‐Yun</creator><creator>Zhu, Bao‐He</creator><creator>Zhang, Chang‐Hua</creator><creator>Yang, Dong‐Jie</creator><creator>Peng, Jian‐Jun</creator><creator>Chen, Jian‐Hui</creator><creator>Liu, Fa‐Keng</creator><creator>He, Yu‐Long</creator><general>Blackwell Publishing Ltd</general><general>John Wiley & Sons, Inc</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>8FE</scope><scope>8FH</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>GNUQQ</scope><scope>HCIFZ</scope><scope>LK8</scope><scope>M7P</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>201201</creationdate><title>High CpG island methylator phenotype is associated with lymph node metastasis and prognosis in gastric cancer</title><author>Chen, Hua‐Yun ; Zhu, Bao‐He ; Zhang, Chang‐Hua ; Yang, Dong‐Jie ; Peng, Jian‐Jun ; Chen, Jian‐Hui ; Liu, Fa‐Keng ; He, Yu‐Long</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c4769-2b7e5e8f538f4fe775e79e03c73a48a68444ea9d640dc7e70c55f437d045e90d3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2012</creationdate><topic>Adult</topic><topic>Aged</topic><topic>Aged, 80 and over</topic><topic>Cancer therapies</topic><topic>Capillary electrophoresis</topic><topic>Colorectal cancer</topic><topic>CpG islands</topic><topic>CpG Islands - genetics</topic><topic>DNA Methylation</topic><topic>DNA-Binding Proteins - genetics</topic><topic>Female</topic><topic>Gastric cancer</topic><topic>Gene expression</topic><topic>Gene Expression Regulation, Neoplastic</topic><topic>Genes, Tumor Suppressor</topic><topic>Genetic testing</topic><topic>Helicobacter Infections - genetics</topic><topic>Helicobacter Infections - pathology</topic><topic>Helicobacter Infections - virology</topic><topic>Helicobacter pylori</topic><topic>Helicobacter pylori - genetics</topic><topic>Humans</topic><topic>Insulin-Like Growth Factor Binding Protein 3 - genetics</topic><topic>Insulin-like growth factor-binding protein 3</topic><topic>Lymph nodes</topic><topic>Lymphatic Metastasis</topic><topic>Male</topic><topic>Medical prognosis</topic><topic>Membrane Proteins - genetics</topic><topic>Metastases</topic><topic>Microsatellite Instability</topic><topic>Middle Aged</topic><topic>Mitochondrial Proteins - genetics</topic><topic>Mortality</topic><topic>mRNA</topic><topic>Neoplasm Proteins - genetics</topic><topic>Neoplasm Staging</topic><topic>Original</topic><topic>Phenotype</topic><topic>Phenotypes</topic><topic>Polymerase chain reaction</topic><topic>Prognosis</topic><topic>Real-Time Polymerase Chain Reaction</topic><topic>Receptors, Atrial Natriuretic Factor - genetics</topic><topic>RNA, Neoplasm</topic><topic>Stomach Neoplasms - genetics</topic><topic>Stomach Neoplasms - mortality</topic><topic>Stomach Neoplasms - pathology</topic><topic>Stomach Neoplasms - virology</topic><topic>Survival Rate</topic><topic>Transcription Factors - genetics</topic><topic>Tumors</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Chen, Hua‐Yun</creatorcontrib><creatorcontrib>Zhu, Bao‐He</creatorcontrib><creatorcontrib>Zhang, Chang‐Hua</creatorcontrib><creatorcontrib>Yang, Dong‐Jie</creatorcontrib><creatorcontrib>Peng, Jian‐Jun</creatorcontrib><creatorcontrib>Chen, Jian‐Hui</creatorcontrib><creatorcontrib>Liu, Fa‐Keng</creatorcontrib><creatorcontrib>He, Yu‐Long</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 SciTech Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</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>ProQuest Central Student</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Biological Science Collection</collection><collection>Biological Science Database</collection><collection>Access via ProQuest (Open Access)</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>Cancer science</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext_linktorsrc</fulltext></delivery><addata><au>Chen, Hua‐Yun</au><au>Zhu, Bao‐He</au><au>Zhang, Chang‐Hua</au><au>Yang, Dong‐Jie</au><au>Peng, Jian‐Jun</au><au>Chen, Jian‐Hui</au><au>Liu, Fa‐Keng</au><au>He, Yu‐Long</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>High CpG island methylator phenotype is associated with lymph node metastasis and prognosis in gastric cancer</atitle><jtitle>Cancer science</jtitle><addtitle>Cancer Sci</addtitle><date>2012-01</date><risdate>2012</risdate><volume>103</volume><issue>1</issue><spage>73</spage><epage>79</epage><pages>73-79</pages><issn>1347-9032</issn><eissn>1349-7006</eissn><abstract>Several studies have found that the promoter CpG island is frequently methylated in gastric cancer. The CpG island methylator phenotype (CIMP) defines concordant methylation of multiple promoter CpG island loci in a subset of gastric cancer. However, the relationship between CIMP and lymph node metastasis in gastric cancer is unknown. Our study aimed to characterize the role of CIMP in lymph node metastasis. Clinical specimens from 120 patients were analyzed and PCR was used to detect the methylation status of five genes (ALX4, TMEFF2, CHCHD10, IGFBP3, and NPR1). We measured the level of mRNA for the five genes by real‐time RT‐PCR. Microsatellite instability and Helicobacter pylori infection status were assayed by capillary electrophoresis and real‐time PCR, respectively. DNA methylation in the five genes was correlated with low expression of the respective mRNA. With CIMP as the dependent variable, CIMP‐high gastric cancer tended to show more distant lymph node metastasis, higher pathologic tumor classification, more pathologic metastasis, and higher pathologic TNM status. Microsatellite instability and H. pylori status were not significant predictors of prognosis. CIMP‐high gastric cancer showed significantly worse survival compared with that of CIMP‐low/CIMP‐negative gastric cancer (P < 0.001). Our results show that there is an association between CIMP status and lymph node metastasis in gastric cancer and CIMP‐high was an independent prognostic factor. (Cancer Sci 2012; 103: 73–79)</abstract><cop>Oxford, UK</cop><pub>Blackwell Publishing Ltd</pub><pmid>22017425</pmid><doi>10.1111/j.1349-7006.2011.02129.x</doi><tpages>7</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Adult Aged Aged, 80 and over Cancer therapies Capillary electrophoresis Colorectal cancer CpG islands CpG Islands - genetics DNA Methylation DNA-Binding Proteins - genetics Female Gastric cancer Gene expression Gene Expression Regulation, Neoplastic Genes, Tumor Suppressor Genetic testing Helicobacter Infections - genetics Helicobacter Infections - pathology Helicobacter Infections - virology Helicobacter pylori Helicobacter pylori - genetics Humans Insulin-Like Growth Factor Binding Protein 3 - genetics Insulin-like growth factor-binding protein 3 Lymph nodes Lymphatic Metastasis Male Medical prognosis Membrane Proteins - genetics Metastases Microsatellite Instability Middle Aged Mitochondrial Proteins - genetics Mortality mRNA Neoplasm Proteins - genetics Neoplasm Staging Original Phenotype Phenotypes Polymerase chain reaction Prognosis Real-Time Polymerase Chain Reaction Receptors, Atrial Natriuretic Factor - genetics RNA, Neoplasm Stomach Neoplasms - genetics Stomach Neoplasms - mortality Stomach Neoplasms - pathology Stomach Neoplasms - virology Survival Rate Transcription Factors - genetics Tumors |
| title | High CpG island methylator phenotype is associated with lymph node metastasis and prognosis in gastric cancer |
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