The aspartate metabolism pathway is differentiable in human hepatocellular carcinoma: transcriptomics and 13C-isotope based metabolomics
Hepatocellular carcinoma (HCC), the primary form of human adult liver malignancy, is a highly aggressive tumor with average survival rates that are currently less than a year following diagnosis. Although bioinformatic analyses have indicated differentially expressed genes and cancer related mutatio...
Gespeichert in:
| Veröffentlicht in: | NMR in biomedicine 2014-04, Vol.27 (4), p.381-389 |
|---|---|
| Hauptverfasser: | , , , , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | 389 |
|---|---|
| container_issue | 4 |
| container_start_page | 381 |
| container_title | NMR in biomedicine |
| container_volume | 27 |
| creator | Darpolor, Moses M. Basu, Sankha S. Worth, Andrew Nelson, David S. Clarke-Katzenberg, Regina H. Glickson, Jerry D. Kaplan, David E. Blair, Ian A. |
| description | Hepatocellular carcinoma (HCC), the primary form of human adult liver malignancy, is a highly aggressive tumor with average survival rates that are currently less than a year following diagnosis. Although bioinformatic analyses have indicated differentially expressed genes and cancer related mutations in HCC, integrated genetic and metabolic pathway analyses remain to be investigated. Herein, gene (i.e. messenger RNA, mRNA) enrichment analysis was performed to delineate significant alterations of metabolic pathways in HCC. The objective of this study was to investigate the pathway of aspartate metabolism in HCC of humans. Coupled with transcriptomic (i.e. mRNA) and NMR based metabolomics of human tissue extracts, we utilized liquid chromatography mass spectrometry based metabolomics analysis of stable [U‐13C6]glucose metabolism or [U‐13C5,15N2]glutamine metabolism of HCC cell culture. Our results indicated that aspartate metabolism is a significant and differentiable metabolic pathway of HCC compared with non‐tumor liver (p value |
| doi_str_mv | 10.1002/nbm.3072 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_pubme</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_3962779</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>3244488991</sourcerecordid><originalsourceid>FETCH-LOGICAL-i2442-739618da154e913a3eea9d6b235cda5ae51049c40472ad80d21b2c12ffc5b1703</originalsourceid><addsrcrecordid>eNpVkU9v1DAQxS0EotuCxEewxDnFf-J4zQGJrqClKuVS4GhNnAnrksTBdij7Dfqx8dJSxGXeYX56b0aPkBecHXPGxKupHY8l0-IRWXFmTMVrIx6TFTNKVLJeswNymNI1Y2xdS_GUHIi6NlryZkVur7ZIIc0QM2SkI2Zow-DTSGfI2xvYUZ9o5_seI07ZQzsg9RPdLiOUiQUKDodhGSBSB9H5KYzwmuYIU3LRzzmM3iUKU0e53FQ-hRxmpC0k7P6m_UGekSc9DAmf3-sR-fz-3dXmrLr4dPph8_ai8uVoUWlpGr7ugKsaDZcgEcF0TSukch0oQMVZbVzNai2gW7NO8FY4LvreqZZrJo_ImzvfeWlH7Fz5KsJg5-hHiDsbwNv_N5Pf2m_hpy3BQmtTDF7eG8TwY8GU7XVY4lRutlyxRnMlmCxUdUfd-AF3D_ac2X1hthRm94XZy5OPe_3H-5Tx1wMP8btttNTKfr08tSeqOW82X87sufwNp0Cbjg</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>1506715203</pqid></control><display><type>article</type><title>The aspartate metabolism pathway is differentiable in human hepatocellular carcinoma: transcriptomics and 13C-isotope based metabolomics</title><source>Wiley Online Library Journals Frontfile Complete</source><creator>Darpolor, Moses M. ; Basu, Sankha S. ; Worth, Andrew ; Nelson, David S. ; Clarke-Katzenberg, Regina H. ; Glickson, Jerry D. ; Kaplan, David E. ; Blair, Ian A.</creator><creatorcontrib>Darpolor, Moses M. ; Basu, Sankha S. ; Worth, Andrew ; Nelson, David S. ; Clarke-Katzenberg, Regina H. ; Glickson, Jerry D. ; Kaplan, David E. ; Blair, Ian A.</creatorcontrib><description>Hepatocellular carcinoma (HCC), the primary form of human adult liver malignancy, is a highly aggressive tumor with average survival rates that are currently less than a year following diagnosis. Although bioinformatic analyses have indicated differentially expressed genes and cancer related mutations in HCC, integrated genetic and metabolic pathway analyses remain to be investigated. Herein, gene (i.e. messenger RNA, mRNA) enrichment analysis was performed to delineate significant alterations of metabolic pathways in HCC. The objective of this study was to investigate the pathway of aspartate metabolism in HCC of humans. Coupled with transcriptomic (i.e. mRNA) and NMR based metabolomics of human tissue extracts, we utilized liquid chromatography mass spectrometry based metabolomics analysis of stable [U‐13C6]glucose metabolism or [U‐13C5,15N2]glutamine metabolism of HCC cell culture. Our results indicated that aspartate metabolism is a significant and differentiable metabolic pathway of HCC compared with non‐tumor liver (p value < 0.0001). In addition, branched‐chain amino acid metabolism (p value < 0.0001) and tricarboxylic acid metabolism (p value < 0.0001) are significant and differentiable. Statistical analysis of measurable NMR metabolites indicated that at least two of the group means were significantly different for the metabolites alanine (p value = 0.0013), succinate (p value = 0.0001), lactate (p value = 0.0114), glycerophosphoethanolamine (p value = 0.015), and inorganic phosphate (p value = 0.0001). However, 13C isotopic enrichment analysis of these metabolites revealed less than 50% isotopic enrichment with either stable [U‐13C6]glucose metabolism or [U‐13C5,15N2]glutamine. This may indicate the differential account of total metabolite pool versus de novo metabolites from a 13C labeled substrate. The ultimate translation of these findings will be to determine putative enzyme activity via 13C labeling, to investigate targeted therapeutics against these enzymes, and to optimize the in vivo performance of 13C MRI techniques. Copyright © 2014 John Wiley & Sons, Ltd.
Although aspartate aminotransaminase is a well known enzyme for the test of liver function, comprehensive pathway analysis of aspartate metabolism in human hepatocellular carcinoma (HCC) has not being performed. Herein, we identified significant enrichment of the aspartate metabolic pathway in HCC as compared with non‐tumor liver. In addition, metabolomics based analyses revealed the putative metabolites. To our knowledge, this study presents the first comprehensive insight into aspartate metabolism in HCC.</description><identifier>ISSN: 0952-3480</identifier><identifier>EISSN: 1099-1492</identifier><identifier>DOI: 10.1002/nbm.3072</identifier><identifier>PMID: 24497316</identifier><language>eng</language><publisher>Oxford: Blackwell Publishing Ltd</publisher><subject>aspartate ; branched-chain amino acids ; cancer ; genetics ; hepatocellular carcinoma ; metabolomics ; transcriptomics</subject><ispartof>NMR in biomedicine, 2014-04, Vol.27 (4), p.381-389</ispartof><rights>Copyright © 2014 John Wiley & Sons, Ltd.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1002%2Fnbm.3072$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1002%2Fnbm.3072$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>230,314,776,780,881,1411,27901,27902,45550,45551</link.rule.ids></links><search><creatorcontrib>Darpolor, Moses M.</creatorcontrib><creatorcontrib>Basu, Sankha S.</creatorcontrib><creatorcontrib>Worth, Andrew</creatorcontrib><creatorcontrib>Nelson, David S.</creatorcontrib><creatorcontrib>Clarke-Katzenberg, Regina H.</creatorcontrib><creatorcontrib>Glickson, Jerry D.</creatorcontrib><creatorcontrib>Kaplan, David E.</creatorcontrib><creatorcontrib>Blair, Ian A.</creatorcontrib><title>The aspartate metabolism pathway is differentiable in human hepatocellular carcinoma: transcriptomics and 13C-isotope based metabolomics</title><title>NMR in biomedicine</title><addtitle>NMR Biomed</addtitle><description>Hepatocellular carcinoma (HCC), the primary form of human adult liver malignancy, is a highly aggressive tumor with average survival rates that are currently less than a year following diagnosis. Although bioinformatic analyses have indicated differentially expressed genes and cancer related mutations in HCC, integrated genetic and metabolic pathway analyses remain to be investigated. Herein, gene (i.e. messenger RNA, mRNA) enrichment analysis was performed to delineate significant alterations of metabolic pathways in HCC. The objective of this study was to investigate the pathway of aspartate metabolism in HCC of humans. Coupled with transcriptomic (i.e. mRNA) and NMR based metabolomics of human tissue extracts, we utilized liquid chromatography mass spectrometry based metabolomics analysis of stable [U‐13C6]glucose metabolism or [U‐13C5,15N2]glutamine metabolism of HCC cell culture. Our results indicated that aspartate metabolism is a significant and differentiable metabolic pathway of HCC compared with non‐tumor liver (p value < 0.0001). In addition, branched‐chain amino acid metabolism (p value < 0.0001) and tricarboxylic acid metabolism (p value < 0.0001) are significant and differentiable. Statistical analysis of measurable NMR metabolites indicated that at least two of the group means were significantly different for the metabolites alanine (p value = 0.0013), succinate (p value = 0.0001), lactate (p value = 0.0114), glycerophosphoethanolamine (p value = 0.015), and inorganic phosphate (p value = 0.0001). However, 13C isotopic enrichment analysis of these metabolites revealed less than 50% isotopic enrichment with either stable [U‐13C6]glucose metabolism or [U‐13C5,15N2]glutamine. This may indicate the differential account of total metabolite pool versus de novo metabolites from a 13C labeled substrate. The ultimate translation of these findings will be to determine putative enzyme activity via 13C labeling, to investigate targeted therapeutics against these enzymes, and to optimize the in vivo performance of 13C MRI techniques. Copyright © 2014 John Wiley & Sons, Ltd.
Although aspartate aminotransaminase is a well known enzyme for the test of liver function, comprehensive pathway analysis of aspartate metabolism in human hepatocellular carcinoma (HCC) has not being performed. Herein, we identified significant enrichment of the aspartate metabolic pathway in HCC as compared with non‐tumor liver. In addition, metabolomics based analyses revealed the putative metabolites. To our knowledge, this study presents the first comprehensive insight into aspartate metabolism in HCC.</description><subject>aspartate</subject><subject>branched-chain amino acids</subject><subject>cancer</subject><subject>genetics</subject><subject>hepatocellular carcinoma</subject><subject>metabolomics</subject><subject>transcriptomics</subject><issn>0952-3480</issn><issn>1099-1492</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2014</creationdate><recordtype>article</recordtype><recordid>eNpVkU9v1DAQxS0EotuCxEewxDnFf-J4zQGJrqClKuVS4GhNnAnrksTBdij7Dfqx8dJSxGXeYX56b0aPkBecHXPGxKupHY8l0-IRWXFmTMVrIx6TFTNKVLJeswNymNI1Y2xdS_GUHIi6NlryZkVur7ZIIc0QM2SkI2Zow-DTSGfI2xvYUZ9o5_seI07ZQzsg9RPdLiOUiQUKDodhGSBSB9H5KYzwmuYIU3LRzzmM3iUKU0e53FQ-hRxmpC0k7P6m_UGekSc9DAmf3-sR-fz-3dXmrLr4dPph8_ai8uVoUWlpGr7ugKsaDZcgEcF0TSukch0oQMVZbVzNai2gW7NO8FY4LvreqZZrJo_ImzvfeWlH7Fz5KsJg5-hHiDsbwNv_N5Pf2m_hpy3BQmtTDF7eG8TwY8GU7XVY4lRutlyxRnMlmCxUdUfd-AF3D_ac2X1hthRm94XZy5OPe_3H-5Tx1wMP8btttNTKfr08tSeqOW82X87sufwNp0Cbjg</recordid><startdate>201404</startdate><enddate>201404</enddate><creator>Darpolor, Moses M.</creator><creator>Basu, Sankha S.</creator><creator>Worth, Andrew</creator><creator>Nelson, David S.</creator><creator>Clarke-Katzenberg, Regina H.</creator><creator>Glickson, Jerry D.</creator><creator>Kaplan, David E.</creator><creator>Blair, Ian A.</creator><general>Blackwell Publishing Ltd</general><general>Wiley Subscription Services, Inc</general><scope>BSCLL</scope><scope>7QO</scope><scope>8FD</scope><scope>FR3</scope><scope>P64</scope><scope>5PM</scope></search><sort><creationdate>201404</creationdate><title>The aspartate metabolism pathway is differentiable in human hepatocellular carcinoma: transcriptomics and 13C-isotope based metabolomics</title><author>Darpolor, Moses M. ; Basu, Sankha S. ; Worth, Andrew ; Nelson, David S. ; Clarke-Katzenberg, Regina H. ; Glickson, Jerry D. ; Kaplan, David E. ; Blair, Ian A.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-i2442-739618da154e913a3eea9d6b235cda5ae51049c40472ad80d21b2c12ffc5b1703</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2014</creationdate><topic>aspartate</topic><topic>branched-chain amino acids</topic><topic>cancer</topic><topic>genetics</topic><topic>hepatocellular carcinoma</topic><topic>metabolomics</topic><topic>transcriptomics</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Darpolor, Moses M.</creatorcontrib><creatorcontrib>Basu, Sankha S.</creatorcontrib><creatorcontrib>Worth, Andrew</creatorcontrib><creatorcontrib>Nelson, David S.</creatorcontrib><creatorcontrib>Clarke-Katzenberg, Regina H.</creatorcontrib><creatorcontrib>Glickson, Jerry D.</creatorcontrib><creatorcontrib>Kaplan, David E.</creatorcontrib><creatorcontrib>Blair, Ian A.</creatorcontrib><collection>Istex</collection><collection>Biotechnology Research Abstracts</collection><collection>Technology Research Database</collection><collection>Engineering Research Database</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>NMR in biomedicine</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Darpolor, Moses M.</au><au>Basu, Sankha S.</au><au>Worth, Andrew</au><au>Nelson, David S.</au><au>Clarke-Katzenberg, Regina H.</au><au>Glickson, Jerry D.</au><au>Kaplan, David E.</au><au>Blair, Ian A.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>The aspartate metabolism pathway is differentiable in human hepatocellular carcinoma: transcriptomics and 13C-isotope based metabolomics</atitle><jtitle>NMR in biomedicine</jtitle><addtitle>NMR Biomed</addtitle><date>2014-04</date><risdate>2014</risdate><volume>27</volume><issue>4</issue><spage>381</spage><epage>389</epage><pages>381-389</pages><issn>0952-3480</issn><eissn>1099-1492</eissn><abstract>Hepatocellular carcinoma (HCC), the primary form of human adult liver malignancy, is a highly aggressive tumor with average survival rates that are currently less than a year following diagnosis. Although bioinformatic analyses have indicated differentially expressed genes and cancer related mutations in HCC, integrated genetic and metabolic pathway analyses remain to be investigated. Herein, gene (i.e. messenger RNA, mRNA) enrichment analysis was performed to delineate significant alterations of metabolic pathways in HCC. The objective of this study was to investigate the pathway of aspartate metabolism in HCC of humans. Coupled with transcriptomic (i.e. mRNA) and NMR based metabolomics of human tissue extracts, we utilized liquid chromatography mass spectrometry based metabolomics analysis of stable [U‐13C6]glucose metabolism or [U‐13C5,15N2]glutamine metabolism of HCC cell culture. Our results indicated that aspartate metabolism is a significant and differentiable metabolic pathway of HCC compared with non‐tumor liver (p value < 0.0001). In addition, branched‐chain amino acid metabolism (p value < 0.0001) and tricarboxylic acid metabolism (p value < 0.0001) are significant and differentiable. Statistical analysis of measurable NMR metabolites indicated that at least two of the group means were significantly different for the metabolites alanine (p value = 0.0013), succinate (p value = 0.0001), lactate (p value = 0.0114), glycerophosphoethanolamine (p value = 0.015), and inorganic phosphate (p value = 0.0001). However, 13C isotopic enrichment analysis of these metabolites revealed less than 50% isotopic enrichment with either stable [U‐13C6]glucose metabolism or [U‐13C5,15N2]glutamine. This may indicate the differential account of total metabolite pool versus de novo metabolites from a 13C labeled substrate. The ultimate translation of these findings will be to determine putative enzyme activity via 13C labeling, to investigate targeted therapeutics against these enzymes, and to optimize the in vivo performance of 13C MRI techniques. Copyright © 2014 John Wiley & Sons, Ltd.
Although aspartate aminotransaminase is a well known enzyme for the test of liver function, comprehensive pathway analysis of aspartate metabolism in human hepatocellular carcinoma (HCC) has not being performed. Herein, we identified significant enrichment of the aspartate metabolic pathway in HCC as compared with non‐tumor liver. In addition, metabolomics based analyses revealed the putative metabolites. To our knowledge, this study presents the first comprehensive insight into aspartate metabolism in HCC.</abstract><cop>Oxford</cop><pub>Blackwell Publishing Ltd</pub><pmid>24497316</pmid><doi>10.1002/nbm.3072</doi><tpages>9</tpages></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0952-3480 |
| ispartof | NMR in biomedicine, 2014-04, Vol.27 (4), p.381-389 |
| issn | 0952-3480 1099-1492 |
| language | eng |
| recordid | cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_3962779 |
| source | Wiley Online Library Journals Frontfile Complete |
| subjects | aspartate branched-chain amino acids cancer genetics hepatocellular carcinoma metabolomics transcriptomics |
| title | The aspartate metabolism pathway is differentiable in human hepatocellular carcinoma: transcriptomics and 13C-isotope based metabolomics |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-02-03T10%3A48%3A16IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_pubme&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=The%20aspartate%20metabolism%20pathway%20is%20differentiable%20in%20human%20hepatocellular%20carcinoma:%20transcriptomics%20and%2013C-isotope%20based%20metabolomics&rft.jtitle=NMR%20in%20biomedicine&rft.au=Darpolor,%20Moses%20M.&rft.date=2014-04&rft.volume=27&rft.issue=4&rft.spage=381&rft.epage=389&rft.pages=381-389&rft.issn=0952-3480&rft.eissn=1099-1492&rft_id=info:doi/10.1002/nbm.3072&rft_dat=%3Cproquest_pubme%3E3244488991%3C/proquest_pubme%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=1506715203&rft_id=info:pmid/24497316&rfr_iscdi=true |