Hypermethylation-repressed methionine adenosyltransferase 1A as a potential biomarker for hepatocellular carcinoma
Aim Methionine adenosyltransferase 1A (MAT1A) is inactivated in HCC and may be stimulated by an epigenetic change involving promoter hypermethylation in hepatocarcinogenesis. However, the possible clinical impact and prognosis of this inactivation have not been investigated. Methods We studied the m...
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| Veröffentlicht in: | Hepatology research 2013-04, Vol.43 (4), p.374-383 |
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| container_title | Hepatology research |
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| creator | Zhang, Jin Gong, Chen Bing, Yuntao Li, Ting Liu, Zhisu Liu, Quanyan |
| description | Aim
Methionine adenosyltransferase 1A (MAT1A) is inactivated in HCC and may be stimulated by an epigenetic change involving promoter hypermethylation in hepatocarcinogenesis. However, the possible clinical impact and prognosis of this inactivation have not been investigated.
Methods
We studied the methylation status of the CpG sites in the promoter region and the mRNA and protein expression of MAT1A in HCC and corresponding adjacent non‐tumor tissues using methylation‐specific polymerase chain reaction, reverse transcription polymerase chain reaction and immunohistochemistry techniques.
Results
MAT1A promoter methylation was significantly higher in HCC than that in adjacent non‐tumor tissues (P |
| doi_str_mv | 10.1111/j.1872-034X.2012.01099.x |
| format | Article |
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Methionine adenosyltransferase 1A (MAT1A) is inactivated in HCC and may be stimulated by an epigenetic change involving promoter hypermethylation in hepatocarcinogenesis. However, the possible clinical impact and prognosis of this inactivation have not been investigated.
Methods
We studied the methylation status of the CpG sites in the promoter region and the mRNA and protein expression of MAT1A in HCC and corresponding adjacent non‐tumor tissues using methylation‐specific polymerase chain reaction, reverse transcription polymerase chain reaction and immunohistochemistry techniques.
Results
MAT1A promoter methylation was significantly higher in HCC than that in adjacent non‐tumor tissues (P < 0.0001). Bisulfite sequencing showed that the four CpG sites were hypermethylated in HCC while hypomethylation was found in the corresponding adjacent non‐tumor tissues. Furthermore, MAT1A methylation was significantly associated with protein expression (P = 0.022). Low expression of MAT1A was correlated with larger tumor size, higher tumor–node–metastasis stage, positive hepatitis B surface antigen status and high α‐fetoprotein (AFP) serum levels (P < 0.05). MAT1A promoter methylation was also correlated with high AFP serum level (P < 0.05). In univariate survival analysis, low expression of MAT1A was significantly associated with shortened patient survival (P < 0.001). Furthermore, in multivariate analysis, MAT1A expression was found as an independent prognostic factor (P = 0.016).
Conclusion
Our observations suggest that hypermethylation of the MAT1A promoter may be one of the events in the development of HCC. Low expression of MAT1A is likely involved in the progression of the tumor and was found to be an independent factor for poor prognosis of patients with HCC.</description><identifier>ISSN: 1386-6346</identifier><identifier>EISSN: 1872-034X</identifier><identifier>DOI: 10.1111/j.1872-034X.2012.01099.x</identifier><identifier>PMID: 23072598</identifier><language>eng</language><publisher>Netherlands: Blackwell Publishing Ltd</publisher><subject>hepatocellular carcinoma ; MAT1A ; methylation</subject><ispartof>Hepatology research, 2013-04, Vol.43 (4), p.374-383</ispartof><rights>2012 The Japan Society of Hepatology</rights><rights>2012 The Japan Society of Hepatology.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c5279-a0e8705975d05291726f35d5317cc2fedc386f95f63d3c970581a1c10b940f2b3</citedby><cites>FETCH-LOGICAL-c5279-a0e8705975d05291726f35d5317cc2fedc386f95f63d3c970581a1c10b940f2b3</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.1872-034X.2012.01099.x$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1111%2Fj.1872-034X.2012.01099.x$$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/23072598$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Zhang, Jin</creatorcontrib><creatorcontrib>Gong, Chen</creatorcontrib><creatorcontrib>Bing, Yuntao</creatorcontrib><creatorcontrib>Li, Ting</creatorcontrib><creatorcontrib>Liu, Zhisu</creatorcontrib><creatorcontrib>Liu, Quanyan</creatorcontrib><title>Hypermethylation-repressed methionine adenosyltransferase 1A as a potential biomarker for hepatocellular carcinoma</title><title>Hepatology research</title><addtitle>Hepatol Res</addtitle><description>Aim
Methionine adenosyltransferase 1A (MAT1A) is inactivated in HCC and may be stimulated by an epigenetic change involving promoter hypermethylation in hepatocarcinogenesis. However, the possible clinical impact and prognosis of this inactivation have not been investigated.
Methods
We studied the methylation status of the CpG sites in the promoter region and the mRNA and protein expression of MAT1A in HCC and corresponding adjacent non‐tumor tissues using methylation‐specific polymerase chain reaction, reverse transcription polymerase chain reaction and immunohistochemistry techniques.
Results
MAT1A promoter methylation was significantly higher in HCC than that in adjacent non‐tumor tissues (P < 0.0001). Bisulfite sequencing showed that the four CpG sites were hypermethylated in HCC while hypomethylation was found in the corresponding adjacent non‐tumor tissues. Furthermore, MAT1A methylation was significantly associated with protein expression (P = 0.022). Low expression of MAT1A was correlated with larger tumor size, higher tumor–node–metastasis stage, positive hepatitis B surface antigen status and high α‐fetoprotein (AFP) serum levels (P < 0.05). MAT1A promoter methylation was also correlated with high AFP serum level (P < 0.05). In univariate survival analysis, low expression of MAT1A was significantly associated with shortened patient survival (P < 0.001). Furthermore, in multivariate analysis, MAT1A expression was found as an independent prognostic factor (P = 0.016).
Conclusion
Our observations suggest that hypermethylation of the MAT1A promoter may be one of the events in the development of HCC. Low expression of MAT1A is likely involved in the progression of the tumor and was found to be an independent factor for poor prognosis of patients with HCC.</description><subject>hepatocellular carcinoma</subject><subject>MAT1A</subject><subject>methylation</subject><issn>1386-6346</issn><issn>1872-034X</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2013</creationdate><recordtype>article</recordtype><recordid>eNqNkEtP3DAURi3UCij0L1RedpPUjziON0gUAYNEH6C-dpbHuRYeMnGwM2Ly73E6dNb1xtb1uZ99D0KYkpLm9WlV0kaygvDqT8kIZSWhRKlye4CO9xdv8pk3dVHzqj5C71JaEUIlYdUhOmKcSCZUc4ziYhogrmF8mDoz-tAXEYYIKUGL52qu-B6waaEPaerGaPrkIJoEmJ5jk7DBQxihH73p8NKHtYmPELELET_AYMZgoes2nYnYmmh9n4FT9NaZLsH71_0E_by6_HGxKG6_Xd9cnN8WVjCpCkOgkUQoKVoimKKS1Y6LVnAqrWUOWpunc0q4mrfcqow21FBLyVJVxLElP0Efd7lDDE8bSKNe-zR_x_QQNklTzipVk4rLjDY71MaQUgSnh-jzKJOmRM_G9UrPYvUsVs_G9V_jeptbP7y-slmuod03_lOcgbMd8Ow7mP47WC8uv9_PxxxQ7AJ8GmG7D8iidS25FPr312tNvizu6l93n7XkL9lGoRQ</recordid><startdate>201304</startdate><enddate>201304</enddate><creator>Zhang, Jin</creator><creator>Gong, Chen</creator><creator>Bing, Yuntao</creator><creator>Li, Ting</creator><creator>Liu, Zhisu</creator><creator>Liu, Quanyan</creator><general>Blackwell Publishing Ltd</general><scope>BSCLL</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope></search><sort><creationdate>201304</creationdate><title>Hypermethylation-repressed methionine adenosyltransferase 1A as a potential biomarker for hepatocellular carcinoma</title><author>Zhang, Jin ; Gong, Chen ; Bing, Yuntao ; Li, Ting ; Liu, Zhisu ; Liu, Quanyan</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c5279-a0e8705975d05291726f35d5317cc2fedc386f95f63d3c970581a1c10b940f2b3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2013</creationdate><topic>hepatocellular carcinoma</topic><topic>MAT1A</topic><topic>methylation</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Zhang, Jin</creatorcontrib><creatorcontrib>Gong, Chen</creatorcontrib><creatorcontrib>Bing, Yuntao</creatorcontrib><creatorcontrib>Li, Ting</creatorcontrib><creatorcontrib>Liu, Zhisu</creatorcontrib><creatorcontrib>Liu, Quanyan</creatorcontrib><collection>Istex</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>Hepatology research</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Zhang, Jin</au><au>Gong, Chen</au><au>Bing, Yuntao</au><au>Li, Ting</au><au>Liu, Zhisu</au><au>Liu, Quanyan</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Hypermethylation-repressed methionine adenosyltransferase 1A as a potential biomarker for hepatocellular carcinoma</atitle><jtitle>Hepatology research</jtitle><addtitle>Hepatol Res</addtitle><date>2013-04</date><risdate>2013</risdate><volume>43</volume><issue>4</issue><spage>374</spage><epage>383</epage><pages>374-383</pages><issn>1386-6346</issn><eissn>1872-034X</eissn><abstract>Aim
Methionine adenosyltransferase 1A (MAT1A) is inactivated in HCC and may be stimulated by an epigenetic change involving promoter hypermethylation in hepatocarcinogenesis. However, the possible clinical impact and prognosis of this inactivation have not been investigated.
Methods
We studied the methylation status of the CpG sites in the promoter region and the mRNA and protein expression of MAT1A in HCC and corresponding adjacent non‐tumor tissues using methylation‐specific polymerase chain reaction, reverse transcription polymerase chain reaction and immunohistochemistry techniques.
Results
MAT1A promoter methylation was significantly higher in HCC than that in adjacent non‐tumor tissues (P < 0.0001). Bisulfite sequencing showed that the four CpG sites were hypermethylated in HCC while hypomethylation was found in the corresponding adjacent non‐tumor tissues. Furthermore, MAT1A methylation was significantly associated with protein expression (P = 0.022). Low expression of MAT1A was correlated with larger tumor size, higher tumor–node–metastasis stage, positive hepatitis B surface antigen status and high α‐fetoprotein (AFP) serum levels (P < 0.05). MAT1A promoter methylation was also correlated with high AFP serum level (P < 0.05). In univariate survival analysis, low expression of MAT1A was significantly associated with shortened patient survival (P < 0.001). Furthermore, in multivariate analysis, MAT1A expression was found as an independent prognostic factor (P = 0.016).
Conclusion
Our observations suggest that hypermethylation of the MAT1A promoter may be one of the events in the development of HCC. Low expression of MAT1A is likely involved in the progression of the tumor and was found to be an independent factor for poor prognosis of patients with HCC.</abstract><cop>Netherlands</cop><pub>Blackwell Publishing Ltd</pub><pmid>23072598</pmid><doi>10.1111/j.1872-034X.2012.01099.x</doi><tpages>10</tpages></addata></record> |
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| ispartof | Hepatology research, 2013-04, Vol.43 (4), p.374-383 |
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| language | eng |
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| source | Wiley Online Library Journals Frontfile Complete |
| subjects | hepatocellular carcinoma MAT1A methylation |
| title | Hypermethylation-repressed methionine adenosyltransferase 1A as a potential biomarker for hepatocellular carcinoma |
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