Global metabolomic profiling of uterine leiomyomas
Background: Uterine leiomyomas can be classified into molecularly distinct subtypes according to their genetic triggers: MED12 mutations, HMGA2 upregulation, or inactivation of FH . The aim of this study was to identify metabolites and metabolic pathways that are dysregulated in different subtypes o...
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| Veröffentlicht in: | British journal of cancer 2017-12, Vol.117 (12), p.1855-1864 |
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| creator | Heinonen, Hanna-Riikka Mehine, Miika Mäkinen, Netta Pasanen, Annukka Pitkänen, Esa Karhu, Auli Sarvilinna, Nanna S Sjöberg, Jari Heikinheimo, Oskari Bützow, Ralf Aaltonen, Lauri A Kaasinen, Eevi |
| description | Background:
Uterine leiomyomas can be classified into molecularly distinct subtypes according to their genetic triggers:
MED12
mutations,
HMGA2
upregulation, or inactivation of
FH
. The aim of this study was to identify metabolites and metabolic pathways that are dysregulated in different subtypes of leiomyomas.
Methods:
We performed global metabolomic profiling of 25 uterine leiomyomas and 17 corresponding myometrium specimens using liquid chromatography–tandem mass spectroscopy.
Results:
A total of 641 metabolites were detected. All leiomyomas displayed reduced homocarnosine and haeme metabolite levels. We identified a clearly distinct metabolomic profile for leiomyomas of the
FH
subtype, characterised by metabolic alterations in the tricarboxylic acid cycle and pentose phosphate pathways, and increased levels of multiple lipids and amino acids. Several metabolites were uniquely elevated in leiomyomas of the
FH
subtype, including N6-succinyladenosine and argininosuccinate, serving as potential biomarkers for
FH
deficiency. In contrast, leiomyomas of the
MED12
subtype displayed reduced levels of vitamin A, multiple membrane lipids and amino acids, and dysregulation of vitamin C metabolism, a finding which was also compatible with gene expression data.
Conclusions:
The study reveals the metabolomic heterogeneity of leiomyomas and provides the requisite framework for strategies designed to target metabolic alterations promoting the growth of these prevalent tumours. |
| doi_str_mv | 10.1038/bjc.2017.361 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_swepu</sourceid><recordid>TN_cdi_swepub_primary_oai_swepub_ki_se_493064</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>1973009895</sourcerecordid><originalsourceid>FETCH-LOGICAL-c538t-60207ff76dc94fcc616668575e703e02c6f578855577e097b823da0a4620fb2c3</originalsourceid><addsrcrecordid>eNp1kUlv2zAQhYmiQeIst54LAb1GzpAUOeSlQBFkAwLkkpwJiiZduZLoUnKL_PvQ8BIHaE9c5ntvyHmEfKEwpcDVVb1wUwYUp1zST2RCBWclVQw_kwkAYAmawQk5HYZFPmpQeExOmAbkkssJYXdtrG1bdH60dWxj17himWJo2qafFzEUq9GnpvdF65vYvcbODufkKNh28Bfb9Yy83N48X9-Xj093D9c_HksnuBpLCQwwBJQzp6vgnKRSSiVQeATugTkZBColhED0oLFWjM8s2EoyCDVz_IyUG9_hr1-uarNMTWfTq4m2MdurX3nnTaU5yCrz-r98_tLsXbQTUo4MVMUwa79vtBno_Mz5fky2_WjxodI3P808_jECma5w3fzb1iDF3ys_jGYRV6nP8zFUI8-TV1pk6nJDuRSHIfmw70DBrNM0OU2zTtPkNDP-9fBVe3gX38GIcqmf-3TQ9V-Gb59Zqpw</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>1973009895</pqid></control><display><type>article</type><title>Global metabolomic profiling of uterine leiomyomas</title><source>MEDLINE</source><source>SWEPUB Freely available online</source><source>Nature_系列刊</source><source>EZB-FREE-00999 freely available EZB journals</source><source>PubMed Central</source><creator>Heinonen, Hanna-Riikka ; Mehine, Miika ; Mäkinen, Netta ; Pasanen, Annukka ; Pitkänen, Esa ; Karhu, Auli ; Sarvilinna, Nanna S ; Sjöberg, Jari ; Heikinheimo, Oskari ; Bützow, Ralf ; Aaltonen, Lauri A ; Kaasinen, Eevi</creator><creatorcontrib>Heinonen, Hanna-Riikka ; Mehine, Miika ; Mäkinen, Netta ; Pasanen, Annukka ; Pitkänen, Esa ; Karhu, Auli ; Sarvilinna, Nanna S ; Sjöberg, Jari ; Heikinheimo, Oskari ; Bützow, Ralf ; Aaltonen, Lauri A ; Kaasinen, Eevi</creatorcontrib><description>Background:
Uterine leiomyomas can be classified into molecularly distinct subtypes according to their genetic triggers:
MED12
mutations,
HMGA2
upregulation, or inactivation of
FH
. The aim of this study was to identify metabolites and metabolic pathways that are dysregulated in different subtypes of leiomyomas.
Methods:
We performed global metabolomic profiling of 25 uterine leiomyomas and 17 corresponding myometrium specimens using liquid chromatography–tandem mass spectroscopy.
Results:
A total of 641 metabolites were detected. All leiomyomas displayed reduced homocarnosine and haeme metabolite levels. We identified a clearly distinct metabolomic profile for leiomyomas of the
FH
subtype, characterised by metabolic alterations in the tricarboxylic acid cycle and pentose phosphate pathways, and increased levels of multiple lipids and amino acids. Several metabolites were uniquely elevated in leiomyomas of the
FH
subtype, including N6-succinyladenosine and argininosuccinate, serving as potential biomarkers for
FH
deficiency. In contrast, leiomyomas of the
MED12
subtype displayed reduced levels of vitamin A, multiple membrane lipids and amino acids, and dysregulation of vitamin C metabolism, a finding which was also compatible with gene expression data.
Conclusions:
The study reveals the metabolomic heterogeneity of leiomyomas and provides the requisite framework for strategies designed to target metabolic alterations promoting the growth of these prevalent tumours.</description><identifier>ISSN: 0007-0920</identifier><identifier>ISSN: 1532-1827</identifier><identifier>EISSN: 1532-1827</identifier><identifier>DOI: 10.1038/bjc.2017.361</identifier><identifier>PMID: 29073636</identifier><language>eng</language><publisher>London: Nature Publishing Group UK</publisher><subject>631/208/199 ; 631/67/1857 ; 631/80/304 ; 692/4017 ; 692/699/2768 ; Adenosine - analogs & derivatives ; Adenosine - metabolism ; Amino acids ; Amino Acids - metabolism ; Argininosuccinic Acid - metabolism ; Ascorbic acid ; Ascorbic Acid - metabolism ; Biomedical and Life Sciences ; Biomedicine ; Cancer och onkologi ; Cancer Research ; Citric Acid Cycle ; Drug Resistance ; Epidemiology ; Female ; Fibroids ; Fumarate Hydratase - genetics ; Gene expression ; Genetics & Genomics ; genetics-and-genomics ; HMGA2 Protein - genetics ; Humans ; Inactivation ; Klinisk medicin ; Leiomyoma - genetics ; Leiomyoma - metabolism ; Lipid Metabolism ; Lipids ; Liquid chromatography ; Mass spectroscopy ; Mediator Complex - genetics ; Medicin och hälsovetenskap ; Metabolic Networks and Pathways ; Metabolic pathways ; Metabolism ; Metabolites ; Metabolome ; Metabolomics ; Molecular Medicine ; Myometrium ; Oncology ; Pentose ; Pentose Phosphate Pathway ; Phosphates ; Reproduktionsmedicin och gynekologi ; Succinyladenosine ; Tricarboxylic acid cycle ; Tumors ; Uterine Neoplasms - genetics ; Uterine Neoplasms - metabolism ; Uterus ; Vitamin A ; Vitamin A - metabolism ; Vitamin C</subject><ispartof>British journal of cancer, 2017-12, Vol.117 (12), p.1855-1864</ispartof><rights>The Author(s) 2017</rights><rights>Copyright Nature Publishing Group Dec 5, 2017</rights><rights>Copyright © 2017 Cancer Research UK 2017 Cancer Research UK</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c538t-60207ff76dc94fcc616668575e703e02c6f578855577e097b823da0a4620fb2c3</citedby><cites>FETCH-LOGICAL-c538t-60207ff76dc94fcc616668575e703e02c6f578855577e097b823da0a4620fb2c3</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/PMC5729474/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC5729474/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,552,727,780,784,885,27924,27925,53791,53793</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/29073636$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink><backlink>$$Uhttp://kipublications.ki.se/Default.aspx?queryparsed=id:137208427$$DView record from Swedish Publication Index$$Hfree_for_read</backlink></links><search><creatorcontrib>Heinonen, Hanna-Riikka</creatorcontrib><creatorcontrib>Mehine, Miika</creatorcontrib><creatorcontrib>Mäkinen, Netta</creatorcontrib><creatorcontrib>Pasanen, Annukka</creatorcontrib><creatorcontrib>Pitkänen, Esa</creatorcontrib><creatorcontrib>Karhu, Auli</creatorcontrib><creatorcontrib>Sarvilinna, Nanna S</creatorcontrib><creatorcontrib>Sjöberg, Jari</creatorcontrib><creatorcontrib>Heikinheimo, Oskari</creatorcontrib><creatorcontrib>Bützow, Ralf</creatorcontrib><creatorcontrib>Aaltonen, Lauri A</creatorcontrib><creatorcontrib>Kaasinen, Eevi</creatorcontrib><title>Global metabolomic profiling of uterine leiomyomas</title><title>British journal of cancer</title><addtitle>Br J Cancer</addtitle><addtitle>Br J Cancer</addtitle><description>Background:
Uterine leiomyomas can be classified into molecularly distinct subtypes according to their genetic triggers:
MED12
mutations,
HMGA2
upregulation, or inactivation of
FH
. The aim of this study was to identify metabolites and metabolic pathways that are dysregulated in different subtypes of leiomyomas.
Methods:
We performed global metabolomic profiling of 25 uterine leiomyomas and 17 corresponding myometrium specimens using liquid chromatography–tandem mass spectroscopy.
Results:
A total of 641 metabolites were detected. All leiomyomas displayed reduced homocarnosine and haeme metabolite levels. We identified a clearly distinct metabolomic profile for leiomyomas of the
FH
subtype, characterised by metabolic alterations in the tricarboxylic acid cycle and pentose phosphate pathways, and increased levels of multiple lipids and amino acids. Several metabolites were uniquely elevated in leiomyomas of the
FH
subtype, including N6-succinyladenosine and argininosuccinate, serving as potential biomarkers for
FH
deficiency. In contrast, leiomyomas of the
MED12
subtype displayed reduced levels of vitamin A, multiple membrane lipids and amino acids, and dysregulation of vitamin C metabolism, a finding which was also compatible with gene expression data.
Conclusions:
The study reveals the metabolomic heterogeneity of leiomyomas and provides the requisite framework for strategies designed to target metabolic alterations promoting the growth of these prevalent tumours.</description><subject>631/208/199</subject><subject>631/67/1857</subject><subject>631/80/304</subject><subject>692/4017</subject><subject>692/699/2768</subject><subject>Adenosine - analogs & derivatives</subject><subject>Adenosine - metabolism</subject><subject>Amino acids</subject><subject>Amino Acids - metabolism</subject><subject>Argininosuccinic Acid - metabolism</subject><subject>Ascorbic acid</subject><subject>Ascorbic Acid - metabolism</subject><subject>Biomedical and Life Sciences</subject><subject>Biomedicine</subject><subject>Cancer och onkologi</subject><subject>Cancer Research</subject><subject>Citric Acid Cycle</subject><subject>Drug Resistance</subject><subject>Epidemiology</subject><subject>Female</subject><subject>Fibroids</subject><subject>Fumarate Hydratase - genetics</subject><subject>Gene expression</subject><subject>Genetics & Genomics</subject><subject>genetics-and-genomics</subject><subject>HMGA2 Protein - genetics</subject><subject>Humans</subject><subject>Inactivation</subject><subject>Klinisk medicin</subject><subject>Leiomyoma - genetics</subject><subject>Leiomyoma - metabolism</subject><subject>Lipid Metabolism</subject><subject>Lipids</subject><subject>Liquid chromatography</subject><subject>Mass spectroscopy</subject><subject>Mediator Complex - genetics</subject><subject>Medicin och hälsovetenskap</subject><subject>Metabolic Networks and Pathways</subject><subject>Metabolic pathways</subject><subject>Metabolism</subject><subject>Metabolites</subject><subject>Metabolome</subject><subject>Metabolomics</subject><subject>Molecular Medicine</subject><subject>Myometrium</subject><subject>Oncology</subject><subject>Pentose</subject><subject>Pentose Phosphate Pathway</subject><subject>Phosphates</subject><subject>Reproduktionsmedicin och gynekologi</subject><subject>Succinyladenosine</subject><subject>Tricarboxylic acid cycle</subject><subject>Tumors</subject><subject>Uterine Neoplasms - genetics</subject><subject>Uterine Neoplasms - metabolism</subject><subject>Uterus</subject><subject>Vitamin A</subject><subject>Vitamin A - metabolism</subject><subject>Vitamin C</subject><issn>0007-0920</issn><issn>1532-1827</issn><issn>1532-1827</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2017</creationdate><recordtype>article</recordtype><sourceid>C6C</sourceid><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><sourceid>D8T</sourceid><recordid>eNp1kUlv2zAQhYmiQeIst54LAb1GzpAUOeSlQBFkAwLkkpwJiiZduZLoUnKL_PvQ8BIHaE9c5ntvyHmEfKEwpcDVVb1wUwYUp1zST2RCBWclVQw_kwkAYAmawQk5HYZFPmpQeExOmAbkkssJYXdtrG1bdH60dWxj17himWJo2qafFzEUq9GnpvdF65vYvcbODufkKNh28Bfb9Yy83N48X9-Xj093D9c_HksnuBpLCQwwBJQzp6vgnKRSSiVQeATugTkZBColhED0oLFWjM8s2EoyCDVz_IyUG9_hr1-uarNMTWfTq4m2MdurX3nnTaU5yCrz-r98_tLsXbQTUo4MVMUwa79vtBno_Mz5fky2_WjxodI3P808_jECma5w3fzb1iDF3ys_jGYRV6nP8zFUI8-TV1pk6nJDuRSHIfmw70DBrNM0OU2zTtPkNDP-9fBVe3gX38GIcqmf-3TQ9V-Gb59Zqpw</recordid><startdate>20171205</startdate><enddate>20171205</enddate><creator>Heinonen, Hanna-Riikka</creator><creator>Mehine, Miika</creator><creator>Mäkinen, Netta</creator><creator>Pasanen, Annukka</creator><creator>Pitkänen, Esa</creator><creator>Karhu, Auli</creator><creator>Sarvilinna, Nanna S</creator><creator>Sjöberg, Jari</creator><creator>Heikinheimo, Oskari</creator><creator>Bützow, Ralf</creator><creator>Aaltonen, Lauri A</creator><creator>Kaasinen, Eevi</creator><general>Nature Publishing Group UK</general><general>Nature Publishing Group</general><scope>C6C</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>3V.</scope><scope>7RV</scope><scope>7TO</scope><scope>7U9</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AN0</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>KB0</scope><scope>LK8</scope><scope>M0S</scope><scope>M1P</scope><scope>M7P</scope><scope>NAPCQ</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>5PM</scope><scope>ADTPV</scope><scope>AOWAS</scope><scope>D8T</scope><scope>ZZAVC</scope></search><sort><creationdate>20171205</creationdate><title>Global metabolomic profiling of uterine leiomyomas</title><author>Heinonen, Hanna-Riikka ; Mehine, Miika ; Mäkinen, Netta ; Pasanen, Annukka ; Pitkänen, Esa ; Karhu, Auli ; Sarvilinna, Nanna S ; Sjöberg, Jari ; Heikinheimo, Oskari ; Bützow, Ralf ; Aaltonen, Lauri A ; Kaasinen, Eevi</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c538t-60207ff76dc94fcc616668575e703e02c6f578855577e097b823da0a4620fb2c3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2017</creationdate><topic>631/208/199</topic><topic>631/67/1857</topic><topic>631/80/304</topic><topic>692/4017</topic><topic>692/699/2768</topic><topic>Adenosine - analogs & derivatives</topic><topic>Adenosine - metabolism</topic><topic>Amino acids</topic><topic>Amino Acids - metabolism</topic><topic>Argininosuccinic Acid - metabolism</topic><topic>Ascorbic acid</topic><topic>Ascorbic Acid - metabolism</topic><topic>Biomedical and Life Sciences</topic><topic>Biomedicine</topic><topic>Cancer och onkologi</topic><topic>Cancer Research</topic><topic>Citric Acid Cycle</topic><topic>Drug Resistance</topic><topic>Epidemiology</topic><topic>Female</topic><topic>Fibroids</topic><topic>Fumarate Hydratase - genetics</topic><topic>Gene expression</topic><topic>Genetics & Genomics</topic><topic>genetics-and-genomics</topic><topic>HMGA2 Protein - genetics</topic><topic>Humans</topic><topic>Inactivation</topic><topic>Klinisk medicin</topic><topic>Leiomyoma - genetics</topic><topic>Leiomyoma - metabolism</topic><topic>Lipid Metabolism</topic><topic>Lipids</topic><topic>Liquid chromatography</topic><topic>Mass spectroscopy</topic><topic>Mediator Complex - genetics</topic><topic>Medicin och hälsovetenskap</topic><topic>Metabolic Networks and Pathways</topic><topic>Metabolic pathways</topic><topic>Metabolism</topic><topic>Metabolites</topic><topic>Metabolome</topic><topic>Metabolomics</topic><topic>Molecular Medicine</topic><topic>Myometrium</topic><topic>Oncology</topic><topic>Pentose</topic><topic>Pentose Phosphate Pathway</topic><topic>Phosphates</topic><topic>Reproduktionsmedicin och gynekologi</topic><topic>Succinyladenosine</topic><topic>Tricarboxylic acid cycle</topic><topic>Tumors</topic><topic>Uterine Neoplasms - genetics</topic><topic>Uterine Neoplasms - metabolism</topic><topic>Uterus</topic><topic>Vitamin A</topic><topic>Vitamin A - metabolism</topic><topic>Vitamin C</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Heinonen, Hanna-Riikka</creatorcontrib><creatorcontrib>Mehine, Miika</creatorcontrib><creatorcontrib>Mäkinen, Netta</creatorcontrib><creatorcontrib>Pasanen, Annukka</creatorcontrib><creatorcontrib>Pitkänen, Esa</creatorcontrib><creatorcontrib>Karhu, Auli</creatorcontrib><creatorcontrib>Sarvilinna, Nanna S</creatorcontrib><creatorcontrib>Sjöberg, Jari</creatorcontrib><creatorcontrib>Heikinheimo, Oskari</creatorcontrib><creatorcontrib>Bützow, Ralf</creatorcontrib><creatorcontrib>Aaltonen, Lauri A</creatorcontrib><creatorcontrib>Kaasinen, Eevi</creatorcontrib><collection>Springer Nature OA Free Journals</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>ProQuest Nursing and Allied Health Source</collection><collection>Oncogenes and Growth Factors Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>PHMC-Proquest健康医学期刊库</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>Public Health Database</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni)</collection><collection>ProQuest Central</collection><collection>British Nursing Database</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>AUTh Library subscriptions: ProQuest Central</collection><collection>Natural Science Collection</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Nursing & Allied Health Database (Alumni Edition)</collection><collection>ProQuest Biological Science Collection</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>PML(ProQuest Medical Library)</collection><collection>ProQuest Biological Science Journals</collection><collection>Nursing & Allied Health Premium</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>PubMed Central (Full Participant titles)</collection><collection>SwePub</collection><collection>SwePub Articles</collection><collection>SWEPUB Freely available online</collection><collection>SwePub Articles full text</collection><jtitle>British journal of cancer</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Heinonen, Hanna-Riikka</au><au>Mehine, Miika</au><au>Mäkinen, Netta</au><au>Pasanen, Annukka</au><au>Pitkänen, Esa</au><au>Karhu, Auli</au><au>Sarvilinna, Nanna S</au><au>Sjöberg, Jari</au><au>Heikinheimo, Oskari</au><au>Bützow, Ralf</au><au>Aaltonen, Lauri A</au><au>Kaasinen, Eevi</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Global metabolomic profiling of uterine leiomyomas</atitle><jtitle>British journal of cancer</jtitle><stitle>Br J Cancer</stitle><addtitle>Br J Cancer</addtitle><date>2017-12-05</date><risdate>2017</risdate><volume>117</volume><issue>12</issue><spage>1855</spage><epage>1864</epage><pages>1855-1864</pages><issn>0007-0920</issn><issn>1532-1827</issn><eissn>1532-1827</eissn><abstract>Background:
Uterine leiomyomas can be classified into molecularly distinct subtypes according to their genetic triggers:
MED12
mutations,
HMGA2
upregulation, or inactivation of
FH
. The aim of this study was to identify metabolites and metabolic pathways that are dysregulated in different subtypes of leiomyomas.
Methods:
We performed global metabolomic profiling of 25 uterine leiomyomas and 17 corresponding myometrium specimens using liquid chromatography–tandem mass spectroscopy.
Results:
A total of 641 metabolites were detected. All leiomyomas displayed reduced homocarnosine and haeme metabolite levels. We identified a clearly distinct metabolomic profile for leiomyomas of the
FH
subtype, characterised by metabolic alterations in the tricarboxylic acid cycle and pentose phosphate pathways, and increased levels of multiple lipids and amino acids. Several metabolites were uniquely elevated in leiomyomas of the
FH
subtype, including N6-succinyladenosine and argininosuccinate, serving as potential biomarkers for
FH
deficiency. In contrast, leiomyomas of the
MED12
subtype displayed reduced levels of vitamin A, multiple membrane lipids and amino acids, and dysregulation of vitamin C metabolism, a finding which was also compatible with gene expression data.
Conclusions:
The study reveals the metabolomic heterogeneity of leiomyomas and provides the requisite framework for strategies designed to target metabolic alterations promoting the growth of these prevalent tumours.</abstract><cop>London</cop><pub>Nature Publishing Group UK</pub><pmid>29073636</pmid><doi>10.1038/bjc.2017.361</doi><tpages>10</tpages><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0007-0920 |
| ispartof | British journal of cancer, 2017-12, Vol.117 (12), p.1855-1864 |
| issn | 0007-0920 1532-1827 1532-1827 |
| language | eng |
| recordid | cdi_swepub_primary_oai_swepub_ki_se_493064 |
| source | MEDLINE; SWEPUB Freely available online; Nature_系列刊; EZB-FREE-00999 freely available EZB journals; PubMed Central |
| subjects | 631/208/199 631/67/1857 631/80/304 692/4017 692/699/2768 Adenosine - analogs & derivatives Adenosine - metabolism Amino acids Amino Acids - metabolism Argininosuccinic Acid - metabolism Ascorbic acid Ascorbic Acid - metabolism Biomedical and Life Sciences Biomedicine Cancer och onkologi Cancer Research Citric Acid Cycle Drug Resistance Epidemiology Female Fibroids Fumarate Hydratase - genetics Gene expression Genetics & Genomics genetics-and-genomics HMGA2 Protein - genetics Humans Inactivation Klinisk medicin Leiomyoma - genetics Leiomyoma - metabolism Lipid Metabolism Lipids Liquid chromatography Mass spectroscopy Mediator Complex - genetics Medicin och hälsovetenskap Metabolic Networks and Pathways Metabolic pathways Metabolism Metabolites Metabolome Metabolomics Molecular Medicine Myometrium Oncology Pentose Pentose Phosphate Pathway Phosphates Reproduktionsmedicin och gynekologi Succinyladenosine Tricarboxylic acid cycle Tumors Uterine Neoplasms - genetics Uterine Neoplasms - metabolism Uterus Vitamin A Vitamin A - metabolism Vitamin C |
| title | Global metabolomic profiling of uterine leiomyomas |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2024-12-25T07%3A48%3A02IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_swepu&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Global%20metabolomic%20profiling%20of%20uterine%20leiomyomas&rft.jtitle=British%20journal%20of%20cancer&rft.au=Heinonen,%20Hanna-Riikka&rft.date=2017-12-05&rft.volume=117&rft.issue=12&rft.spage=1855&rft.epage=1864&rft.pages=1855-1864&rft.issn=0007-0920&rft.eissn=1532-1827&rft_id=info:doi/10.1038/bjc.2017.361&rft_dat=%3Cproquest_swepu%3E1973009895%3C/proquest_swepu%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=1973009895&rft_id=info:pmid/29073636&rfr_iscdi=true |