Epigenetic methylation and expression of caspase 8 and survivin in hepatocellular carcinoma
Caspase 8 and survivin are known as key molecules of apoptosis in hepatocellular carcinoma (HCC). The purpose of the present study was to investigate the relationship between promoter methylation and expression and apoptotic function of caspase 8 and survivin in HCC. Promoter methylation of the casp...
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| Veröffentlicht in: | Pathology international 2010-03, Vol.60 (3), p.203-211 |
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| creator | Cho, Seok Lee, Jae Hyek Cho, Sung Bum Yoon, Kyeng Won Park, Seon Young Lee, Wan Sik Park, Chang Hwan Joo, Young Eun Kim, Hyun Soo Choi, Sung Kyu Rew, Jong Sun |
| description | Caspase 8 and survivin are known as key molecules of apoptosis in hepatocellular carcinoma (HCC). The purpose of the present study was to investigate the relationship between promoter methylation and expression and apoptotic function of caspase 8 and survivin in HCC. Promoter methylation of the caspase 8 and survivin gene was analyzed in 73 primary HCC using methylation‐specific polymerase chain reaction. The relationship between immunohistochemical expression of gene products and proliferative/apoptotic indices, and clinicopathological parameters was also investigated. Twenty‐five (34%) and 24 (33%) patients had promoter methylation of caspase 8 and survivin gene. Immunohistochemical staining of caspase 8 and survivin was observed in 35 (48%) and 32 (44%). The methylation of caspase 8 and survivin demonstrated a negative correlation with immunohistochemical expression of gene products (P= 0.049 and P= 0.001). Methylation of caspase 8 and positive expression of its gene product was significantly correlated with high apoptotic indices (P= 0.032 and P= 0.026). Nuclear survivin expression was significantly correlated with high proliferative index (P= 0.001). On survival analysis, positive nuclear survivin expression was associated with a poor prognosis in HCC (P= 0.043). In conclusion, epigenetic alteration by promoter methylation of caspase 8 and survivin may constitute an important regulatory mechanism for expression of those genes in HCC. |
| doi_str_mv | 10.1111/j.1440-1827.2009.02507.x |
| format | Article |
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The purpose of the present study was to investigate the relationship between promoter methylation and expression and apoptotic function of caspase 8 and survivin in HCC. Promoter methylation of the caspase 8 and survivin gene was analyzed in 73 primary HCC using methylation‐specific polymerase chain reaction. The relationship between immunohistochemical expression of gene products and proliferative/apoptotic indices, and clinicopathological parameters was also investigated. Twenty‐five (34%) and 24 (33%) patients had promoter methylation of caspase 8 and survivin gene. Immunohistochemical staining of caspase 8 and survivin was observed in 35 (48%) and 32 (44%). The methylation of caspase 8 and survivin demonstrated a negative correlation with immunohistochemical expression of gene products (P= 0.049 and P= 0.001). Methylation of caspase 8 and positive expression of its gene product was significantly correlated with high apoptotic indices (P= 0.032 and P= 0.026). Nuclear survivin expression was significantly correlated with high proliferative index (P= 0.001). On survival analysis, positive nuclear survivin expression was associated with a poor prognosis in HCC (P= 0.043). In conclusion, epigenetic alteration by promoter methylation of caspase 8 and survivin may constitute an important regulatory mechanism for expression of those genes in HCC.</description><identifier>ISSN: 1320-5463</identifier><identifier>EISSN: 1440-1827</identifier><identifier>DOI: 10.1111/j.1440-1827.2009.02507.x</identifier><identifier>PMID: 20403046</identifier><language>eng</language><publisher>Melbourne, Australia: Blackwell Publishing Asia</publisher><subject>Adult ; Aged ; Analysis of Variance ; Apoptosis ; Apoptosis - genetics ; Biomarkers, Tumor - genetics ; Biomarkers, Tumor - metabolism ; Carcinoma, Hepatocellular - genetics ; Carcinoma, Hepatocellular - metabolism ; Carcinoma, Hepatocellular - pathology ; Caspase 8 - genetics ; Caspase 8 - metabolism ; Caspase-8 ; Cell Count ; Cell Proliferation ; Chi-Square Distribution ; DNA methylation ; DNA Methylation - genetics ; Epigenesis, Genetic - genetics ; epigenetics ; Female ; Gene Expression Regulation, Neoplastic ; Hepatocellular carcinoma ; Humans ; Immunohistochemistry ; Inhibitor of Apoptosis Proteins ; Liver Neoplasms - genetics ; Liver Neoplasms - metabolism ; Liver Neoplasms - pathology ; Male ; Microtubule-Associated Proteins - genetics ; Microtubule-Associated Proteins - metabolism ; Middle Aged ; Polymerase chain reaction ; Prognosis ; Promoter Regions, Genetic - genetics ; Survival ; survivin</subject><ispartof>Pathology international, 2010-03, Vol.60 (3), p.203-211</ispartof><rights>2010 The Authors. Journal compilation © 2010 Japanese Society of Pathology</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c4917-f4847bd8734830752323c83e141543d04a312e492a68738a09c5e6443d0711d43</citedby><cites>FETCH-LOGICAL-c4917-f4847bd8734830752323c83e141543d04a312e492a68738a09c5e6443d0711d43</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1111%2Fj.1440-1827.2009.02507.x$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1111%2Fj.1440-1827.2009.02507.x$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>314,776,780,1411,27901,27902,45550,45551</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/20403046$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Cho, Seok</creatorcontrib><creatorcontrib>Lee, Jae Hyek</creatorcontrib><creatorcontrib>Cho, Sung Bum</creatorcontrib><creatorcontrib>Yoon, Kyeng Won</creatorcontrib><creatorcontrib>Park, Seon Young</creatorcontrib><creatorcontrib>Lee, Wan Sik</creatorcontrib><creatorcontrib>Park, Chang Hwan</creatorcontrib><creatorcontrib>Joo, Young Eun</creatorcontrib><creatorcontrib>Kim, Hyun Soo</creatorcontrib><creatorcontrib>Choi, Sung Kyu</creatorcontrib><creatorcontrib>Rew, Jong Sun</creatorcontrib><title>Epigenetic methylation and expression of caspase 8 and survivin in hepatocellular carcinoma</title><title>Pathology international</title><addtitle>Pathol Int</addtitle><description>Caspase 8 and survivin are known as key molecules of apoptosis in hepatocellular carcinoma (HCC). The purpose of the present study was to investigate the relationship between promoter methylation and expression and apoptotic function of caspase 8 and survivin in HCC. Promoter methylation of the caspase 8 and survivin gene was analyzed in 73 primary HCC using methylation‐specific polymerase chain reaction. The relationship between immunohistochemical expression of gene products and proliferative/apoptotic indices, and clinicopathological parameters was also investigated. Twenty‐five (34%) and 24 (33%) patients had promoter methylation of caspase 8 and survivin gene. Immunohistochemical staining of caspase 8 and survivin was observed in 35 (48%) and 32 (44%). The methylation of caspase 8 and survivin demonstrated a negative correlation with immunohistochemical expression of gene products (P= 0.049 and P= 0.001). Methylation of caspase 8 and positive expression of its gene product was significantly correlated with high apoptotic indices (P= 0.032 and P= 0.026). Nuclear survivin expression was significantly correlated with high proliferative index (P= 0.001). On survival analysis, positive nuclear survivin expression was associated with a poor prognosis in HCC (P= 0.043). In conclusion, epigenetic alteration by promoter methylation of caspase 8 and survivin may constitute an important regulatory mechanism for expression of those genes in HCC.</description><subject>Adult</subject><subject>Aged</subject><subject>Analysis of Variance</subject><subject>Apoptosis</subject><subject>Apoptosis - genetics</subject><subject>Biomarkers, Tumor - genetics</subject><subject>Biomarkers, Tumor - metabolism</subject><subject>Carcinoma, Hepatocellular - genetics</subject><subject>Carcinoma, Hepatocellular - metabolism</subject><subject>Carcinoma, Hepatocellular - pathology</subject><subject>Caspase 8 - genetics</subject><subject>Caspase 8 - metabolism</subject><subject>Caspase-8</subject><subject>Cell Count</subject><subject>Cell Proliferation</subject><subject>Chi-Square Distribution</subject><subject>DNA methylation</subject><subject>DNA Methylation - genetics</subject><subject>Epigenesis, Genetic - genetics</subject><subject>epigenetics</subject><subject>Female</subject><subject>Gene Expression Regulation, Neoplastic</subject><subject>Hepatocellular carcinoma</subject><subject>Humans</subject><subject>Immunohistochemistry</subject><subject>Inhibitor of Apoptosis Proteins</subject><subject>Liver Neoplasms - genetics</subject><subject>Liver Neoplasms - metabolism</subject><subject>Liver Neoplasms - pathology</subject><subject>Male</subject><subject>Microtubule-Associated Proteins - genetics</subject><subject>Microtubule-Associated Proteins - metabolism</subject><subject>Middle Aged</subject><subject>Polymerase chain reaction</subject><subject>Prognosis</subject><subject>Promoter Regions, Genetic - genetics</subject><subject>Survival</subject><subject>survivin</subject><issn>1320-5463</issn><issn>1440-1827</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2010</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqNkU9v1DAQxS0EomXhK6DcOCWM7UnsHDigqrSVVgtILa3EwXKTWeol_7CTdvfb43TLXqllyWO93xtb8xhLOGQ8ro-bjCNCyrVQmQAoMxA5qGz7gh0fhJexlgLSHAt5xN6EsAHgShbwmh0JQJCAxTH7eTq4X9TR6KqkpfFu19jR9V1iuzqh7eAphPnar5PKhsEGSvSjFiZ_7-5dl8R9R4Md-4qaZmqsj6CvXNe39i17tbZNoHdP54JdfTm9PDlPl1_PLk4-L9MKS67SNWpUt7VWErUElQspZKUlceQ5yhrQSi4IS2GLyGgLZZVTgbOkOK9RLtiHfd_B938mCqNpXZi_Yzvqp2AUYqFi1_L_pJS61DzCC6b3ZOX7EDytzeBda_3OcDBzBmZj5lGbedRmzsA8ZmC20fr-6ZHptqX6YPw39Ah82gMPrqHdsxubbxeruYr-dO93YaTtwW_9b1MoqXJzvTozP27Eavn98sZcy7-j6aL9</recordid><startdate>201003</startdate><enddate>201003</enddate><creator>Cho, Seok</creator><creator>Lee, Jae Hyek</creator><creator>Cho, Sung Bum</creator><creator>Yoon, Kyeng Won</creator><creator>Park, Seon Young</creator><creator>Lee, Wan Sik</creator><creator>Park, Chang Hwan</creator><creator>Joo, Young Eun</creator><creator>Kim, Hyun Soo</creator><creator>Choi, Sung Kyu</creator><creator>Rew, Jong Sun</creator><general>Blackwell Publishing Asia</general><scope>BSCLL</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>8FD</scope><scope>FR3</scope><scope>P64</scope><scope>RC3</scope></search><sort><creationdate>201003</creationdate><title>Epigenetic methylation and expression of caspase 8 and survivin in hepatocellular carcinoma</title><author>Cho, Seok ; Lee, Jae Hyek ; Cho, Sung Bum ; Yoon, Kyeng Won ; Park, Seon Young ; Lee, Wan Sik ; Park, Chang Hwan ; Joo, Young Eun ; Kim, Hyun Soo ; Choi, Sung Kyu ; Rew, Jong Sun</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c4917-f4847bd8734830752323c83e141543d04a312e492a68738a09c5e6443d0711d43</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2010</creationdate><topic>Adult</topic><topic>Aged</topic><topic>Analysis of Variance</topic><topic>Apoptosis</topic><topic>Apoptosis - genetics</topic><topic>Biomarkers, Tumor - genetics</topic><topic>Biomarkers, Tumor - metabolism</topic><topic>Carcinoma, Hepatocellular - genetics</topic><topic>Carcinoma, Hepatocellular - metabolism</topic><topic>Carcinoma, Hepatocellular - pathology</topic><topic>Caspase 8 - genetics</topic><topic>Caspase 8 - metabolism</topic><topic>Caspase-8</topic><topic>Cell Count</topic><topic>Cell Proliferation</topic><topic>Chi-Square Distribution</topic><topic>DNA methylation</topic><topic>DNA Methylation - genetics</topic><topic>Epigenesis, Genetic - genetics</topic><topic>epigenetics</topic><topic>Female</topic><topic>Gene Expression Regulation, Neoplastic</topic><topic>Hepatocellular carcinoma</topic><topic>Humans</topic><topic>Immunohistochemistry</topic><topic>Inhibitor of Apoptosis Proteins</topic><topic>Liver Neoplasms - genetics</topic><topic>Liver Neoplasms - metabolism</topic><topic>Liver Neoplasms - pathology</topic><topic>Male</topic><topic>Microtubule-Associated Proteins - genetics</topic><topic>Microtubule-Associated Proteins - metabolism</topic><topic>Middle Aged</topic><topic>Polymerase chain reaction</topic><topic>Prognosis</topic><topic>Promoter Regions, Genetic - genetics</topic><topic>Survival</topic><topic>survivin</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Cho, Seok</creatorcontrib><creatorcontrib>Lee, Jae Hyek</creatorcontrib><creatorcontrib>Cho, Sung Bum</creatorcontrib><creatorcontrib>Yoon, Kyeng Won</creatorcontrib><creatorcontrib>Park, Seon Young</creatorcontrib><creatorcontrib>Lee, Wan Sik</creatorcontrib><creatorcontrib>Park, Chang Hwan</creatorcontrib><creatorcontrib>Joo, Young Eun</creatorcontrib><creatorcontrib>Kim, Hyun Soo</creatorcontrib><creatorcontrib>Choi, Sung Kyu</creatorcontrib><creatorcontrib>Rew, Jong Sun</creatorcontrib><collection>Istex</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>Technology Research Database</collection><collection>Engineering Research Database</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Genetics Abstracts</collection><jtitle>Pathology international</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Cho, Seok</au><au>Lee, Jae Hyek</au><au>Cho, Sung Bum</au><au>Yoon, Kyeng Won</au><au>Park, Seon Young</au><au>Lee, Wan Sik</au><au>Park, Chang Hwan</au><au>Joo, Young Eun</au><au>Kim, Hyun Soo</au><au>Choi, Sung Kyu</au><au>Rew, Jong Sun</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Epigenetic methylation and expression of caspase 8 and survivin in hepatocellular carcinoma</atitle><jtitle>Pathology international</jtitle><addtitle>Pathol Int</addtitle><date>2010-03</date><risdate>2010</risdate><volume>60</volume><issue>3</issue><spage>203</spage><epage>211</epage><pages>203-211</pages><issn>1320-5463</issn><eissn>1440-1827</eissn><abstract>Caspase 8 and survivin are known as key molecules of apoptosis in hepatocellular carcinoma (HCC). The purpose of the present study was to investigate the relationship between promoter methylation and expression and apoptotic function of caspase 8 and survivin in HCC. Promoter methylation of the caspase 8 and survivin gene was analyzed in 73 primary HCC using methylation‐specific polymerase chain reaction. The relationship between immunohistochemical expression of gene products and proliferative/apoptotic indices, and clinicopathological parameters was also investigated. Twenty‐five (34%) and 24 (33%) patients had promoter methylation of caspase 8 and survivin gene. Immunohistochemical staining of caspase 8 and survivin was observed in 35 (48%) and 32 (44%). The methylation of caspase 8 and survivin demonstrated a negative correlation with immunohistochemical expression of gene products (P= 0.049 and P= 0.001). Methylation of caspase 8 and positive expression of its gene product was significantly correlated with high apoptotic indices (P= 0.032 and P= 0.026). Nuclear survivin expression was significantly correlated with high proliferative index (P= 0.001). On survival analysis, positive nuclear survivin expression was associated with a poor prognosis in HCC (P= 0.043). In conclusion, epigenetic alteration by promoter methylation of caspase 8 and survivin may constitute an important regulatory mechanism for expression of those genes in HCC.</abstract><cop>Melbourne, Australia</cop><pub>Blackwell Publishing Asia</pub><pmid>20403046</pmid><doi>10.1111/j.1440-1827.2009.02507.x</doi><tpages>9</tpages></addata></record> |
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| subjects | Adult Aged Analysis of Variance Apoptosis Apoptosis - genetics Biomarkers, Tumor - genetics Biomarkers, Tumor - metabolism Carcinoma, Hepatocellular - genetics Carcinoma, Hepatocellular - metabolism Carcinoma, Hepatocellular - pathology Caspase 8 - genetics Caspase 8 - metabolism Caspase-8 Cell Count Cell Proliferation Chi-Square Distribution DNA methylation DNA Methylation - genetics Epigenesis, Genetic - genetics epigenetics Female Gene Expression Regulation, Neoplastic Hepatocellular carcinoma Humans Immunohistochemistry Inhibitor of Apoptosis Proteins Liver Neoplasms - genetics Liver Neoplasms - metabolism Liver Neoplasms - pathology Male Microtubule-Associated Proteins - genetics Microtubule-Associated Proteins - metabolism Middle Aged Polymerase chain reaction Prognosis Promoter Regions, Genetic - genetics Survival survivin |
| title | Epigenetic methylation and expression of caspase 8 and survivin in hepatocellular carcinoma |
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