Glycolysis gene expression analysis and selective metabolic advantage in the clinical progression of colorectal cancer
Production of lactate even in the presence of sufficient levels of oxygen (aerobic glycolysis) seems the prevalent energy metabolism pathway in cancer cells. The analysis of altered expression of effectors causing redirection of glucose metabolism would help to characterize this phenomenon with poss...
Gespeichert in:
| Veröffentlicht in: | The pharmacogenomics journal 2017-06, Vol.17 (3), p.258-264 |
|---|---|
| Hauptverfasser: | , , , , , , , , , , , , , , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | 264 |
|---|---|
| container_issue | 3 |
| container_start_page | 258 |
| container_title | The pharmacogenomics journal |
| container_volume | 17 |
| creator | Graziano, F Ruzzo, A Giacomini, E Ricciardi, T Aprile, G Loupakis, F Lorenzini, P Ongaro, E Zoratto, F Catalano, V Sarti, D Rulli, E Cremolini, C De Nictolis, M De Maglio, G Falcone, A Fiorentini, G Magnani, M |
| description | Production of lactate even in the presence of sufficient levels of oxygen (aerobic glycolysis) seems the prevalent energy metabolism pathway in cancer cells. The analysis of altered expression of effectors causing redirection of glucose metabolism would help to characterize this phenomenon with possible therapeutic implications. We analyzed mRNA expression of the key enzymes involved in aerobic glycolysis in normal mucosa (NM), primary tumor (PT) and liver metastasis (LM) of colorectal cancer (CRC) patients (pts) who underwent primary tumor surgery and liver metastasectomy. Tissues of 48 CRC pts were analyzed by RT-qPCR for mRNA expression of the following genes: hexokinase-1 (
HK-1
) and 2 (
HK-2
), embryonic pyruvate kinase (
PKM-2
), lactate dehydrogenase-A (
LDH-A
), glucose transporter-1 (
GLUT-1
), voltage-dependent anion-selective channel protein-1 (
VDAC-1
). Differences in the expression of the candidate genes between tissues and associations with clinical/pathologic features were studied.
GLUT-1
,
LDH-A
,
HK-1, PKM-2
and
VDAC-1
mRNA expression levels were significantly higher in PT/LM tissues compared with NM. There was a trend for higher expression of these genes in LM compared with PT tissues, but differences were statistically significant for
LDH-A
expression only.
RAS
mutation-positive disease was associated with high
GLUT-1
mRNA expression levels only. Right-sided colon tumors showed significantly higher
GLUT-1
,
PKM-2
and
LDH-A
mRNA expression levels. High glycolytic profile was significantly associated with poor prognosis in 20 metastatic,
RAS
-mutated pts treated with first-line chemotherapy plus Bevacizumab. Altered expression of effectors associated with upregulated glucose uptake and aerobic glycolysis occurs in CRC tissues. Additional analyses are warranted for addressing the role of these changes in anti-angiogenic resistance and for developing novel therapeutics. |
| doi_str_mv | 10.1038/tpj.2016.13 |
| format | Article |
| fullrecord | <record><control><sourceid>gale_proqu</sourceid><recordid>TN_cdi_proquest_miscellaneous_1906461163</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><galeid>A689285908</galeid><sourcerecordid>A689285908</sourcerecordid><originalsourceid>FETCH-LOGICAL-c549t-638fb8943a53dabb7b0aa685945a0ff48d8e034384a2fae45bb746e9ed0f49643</originalsourceid><addsrcrecordid>eNqNks9rFDEUxwdRbK2evEvAi6C75vcmx1JqFQpeFLyFN5k3a5bZZE1ml-5_b6bbapVSJYeEvM_7fpPHt2leMjpnVJj342Y155TpOROPmmMmF2LGmKKPr890xrX9dtQ8K2VFK8QW5mlzVO_4ght53Owuhr1Pw76EQpYYkeDVJmMpIUUCEQ4FiB0pOKAfww7JGkdo0xA8gW4HcYQlkhDJ-B2JH0IMHgayyWl5K5N6Uh1Sru214iF6zM-bJz0MBV_c7CfN1w_nX84-zi4_X3w6O72ceSXtONPC9K2xUoASHbTtoqUA2igrFdC-l6YzSIUURgLvAaWqiNRosaO9tFqKk-bNQbc-6McWy-jWoXgcBoiYtsUxS7XUjGnxb9RwrZXVnFb09V_oKm1znVZxXDOlBDVWPERVW2oEZYr_ppYwoAuxT2MGP1m7U20sr5-t6EOUtFxKodXkOL-HqqvDdfApYh_q_R-y_9Vw1-HtocHnVErG3m1yWEPeO0bdlEZX0-imNDo20a9uJrBt19j9Ym_jV4F3B6DUUlxivjOie_R-Amhe5os</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>1900830152</pqid></control><display><type>article</type><title>Glycolysis gene expression analysis and selective metabolic advantage in the clinical progression of colorectal cancer</title><source>MEDLINE</source><source>Alma/SFX Local Collection</source><creator>Graziano, F ; Ruzzo, A ; Giacomini, E ; Ricciardi, T ; Aprile, G ; Loupakis, F ; Lorenzini, P ; Ongaro, E ; Zoratto, F ; Catalano, V ; Sarti, D ; Rulli, E ; Cremolini, C ; De Nictolis, M ; De Maglio, G ; Falcone, A ; Fiorentini, G ; Magnani, M</creator><creatorcontrib>Graziano, F ; Ruzzo, A ; Giacomini, E ; Ricciardi, T ; Aprile, G ; Loupakis, F ; Lorenzini, P ; Ongaro, E ; Zoratto, F ; Catalano, V ; Sarti, D ; Rulli, E ; Cremolini, C ; De Nictolis, M ; De Maglio, G ; Falcone, A ; Fiorentini, G ; Magnani, M</creatorcontrib><description>Production of lactate even in the presence of sufficient levels of oxygen (aerobic glycolysis) seems the prevalent energy metabolism pathway in cancer cells. The analysis of altered expression of effectors causing redirection of glucose metabolism would help to characterize this phenomenon with possible therapeutic implications. We analyzed mRNA expression of the key enzymes involved in aerobic glycolysis in normal mucosa (NM), primary tumor (PT) and liver metastasis (LM) of colorectal cancer (CRC) patients (pts) who underwent primary tumor surgery and liver metastasectomy. Tissues of 48 CRC pts were analyzed by RT-qPCR for mRNA expression of the following genes: hexokinase-1 (
HK-1
) and 2 (
HK-2
), embryonic pyruvate kinase (
PKM-2
), lactate dehydrogenase-A (
LDH-A
), glucose transporter-1 (
GLUT-1
), voltage-dependent anion-selective channel protein-1 (
VDAC-1
). Differences in the expression of the candidate genes between tissues and associations with clinical/pathologic features were studied.
GLUT-1
,
LDH-A
,
HK-1, PKM-2
and
VDAC-1
mRNA expression levels were significantly higher in PT/LM tissues compared with NM. There was a trend for higher expression of these genes in LM compared with PT tissues, but differences were statistically significant for
LDH-A
expression only.
RAS
mutation-positive disease was associated with high
GLUT-1
mRNA expression levels only. Right-sided colon tumors showed significantly higher
GLUT-1
,
PKM-2
and
LDH-A
mRNA expression levels. High glycolytic profile was significantly associated with poor prognosis in 20 metastatic,
RAS
-mutated pts treated with first-line chemotherapy plus Bevacizumab. Altered expression of effectors associated with upregulated glucose uptake and aerobic glycolysis occurs in CRC tissues. Additional analyses are warranted for addressing the role of these changes in anti-angiogenic resistance and for developing novel therapeutics.</description><identifier>ISSN: 1470-269X</identifier><identifier>EISSN: 1473-1150</identifier><identifier>DOI: 10.1038/tpj.2016.13</identifier><identifier>PMID: 26927284</identifier><language>eng</language><publisher>London: Nature Publishing Group UK</publisher><subject>631/67/68 ; 692/308/575 ; Aged ; Analysis ; Angiogenesis ; Angiogenesis Inhibitors - therapeutic use ; Antineoplastic Combined Chemotherapy Protocols - therapeutic use ; Bevacizumab ; Biomarkers, Tumor - genetics ; Biomedical and Life Sciences ; Biomedicine ; Cancer ; Care and treatment ; Chemotherapy ; Colectomy ; Colorectal cancer ; Colorectal carcinoma ; Colorectal Neoplasms - enzymology ; Colorectal Neoplasms - genetics ; Colorectal Neoplasms - pathology ; Colorectal Neoplasms - therapy ; Development and progression ; Disease Progression ; Drug Resistance, Neoplasm - genetics ; Embryos ; Energy metabolism ; Enzymes ; Female ; Gene Expression ; Gene Expression Profiling ; Gene Expression Regulation, Enzymologic ; Gene Expression Regulation, Neoplastic ; Genetic aspects ; Genetic Predisposition to Disease ; Glucose ; Glucose metabolism ; Glucose transporter ; Glycolysis ; Glycolysis - genetics ; Health aspects ; Hepatectomy ; Hexokinase ; Human Genetics ; Humans ; Identification and classification ; Italy ; Kaplan-Meier Estimate ; Kinases ; L-Lactate dehydrogenase ; Lactic acid ; Liver ; Liver Neoplasms - enzymology ; Liver Neoplasms - genetics ; Liver Neoplasms - secondary ; Liver Neoplasms - therapy ; Male ; Messenger RNA ; Metabolism ; Metastasectomy - methods ; Metastases ; Methods ; Mucosa ; Mutation ; Oncology ; original-article ; Pharmacogenetics ; Pharmacogenomic Variants ; Pharmacotherapy ; Phenotype ; Polymerase chain reaction ; Prognosis ; Psychopharmacology ; Pyruvate kinase ; Pyruvic acid ; Ras protein ; Retrospective Studies ; Risk Factors ; RNA, Messenger - genetics ; Statistical analysis ; Time Factors ; Treatment Outcome ; Tumors</subject><ispartof>The pharmacogenomics journal, 2017-06, Vol.17 (3), p.258-264</ispartof><rights>Macmillan Publishers Limited 2017</rights><rights>COPYRIGHT 2017 Nature Publishing Group</rights><rights>Copyright Nature Publishing Group Jun 2017</rights><rights>Macmillan Publishers Limited 2017.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c549t-638fb8943a53dabb7b0aa685945a0ff48d8e034384a2fae45bb746e9ed0f49643</citedby><cites>FETCH-LOGICAL-c549t-638fb8943a53dabb7b0aa685945a0ff48d8e034384a2fae45bb746e9ed0f49643</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,777,781,27905,27906</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/26927284$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Graziano, F</creatorcontrib><creatorcontrib>Ruzzo, A</creatorcontrib><creatorcontrib>Giacomini, E</creatorcontrib><creatorcontrib>Ricciardi, T</creatorcontrib><creatorcontrib>Aprile, G</creatorcontrib><creatorcontrib>Loupakis, F</creatorcontrib><creatorcontrib>Lorenzini, P</creatorcontrib><creatorcontrib>Ongaro, E</creatorcontrib><creatorcontrib>Zoratto, F</creatorcontrib><creatorcontrib>Catalano, V</creatorcontrib><creatorcontrib>Sarti, D</creatorcontrib><creatorcontrib>Rulli, E</creatorcontrib><creatorcontrib>Cremolini, C</creatorcontrib><creatorcontrib>De Nictolis, M</creatorcontrib><creatorcontrib>De Maglio, G</creatorcontrib><creatorcontrib>Falcone, A</creatorcontrib><creatorcontrib>Fiorentini, G</creatorcontrib><creatorcontrib>Magnani, M</creatorcontrib><title>Glycolysis gene expression analysis and selective metabolic advantage in the clinical progression of colorectal cancer</title><title>The pharmacogenomics journal</title><addtitle>Pharmacogenomics J</addtitle><addtitle>Pharmacogenomics J</addtitle><description>Production of lactate even in the presence of sufficient levels of oxygen (aerobic glycolysis) seems the prevalent energy metabolism pathway in cancer cells. The analysis of altered expression of effectors causing redirection of glucose metabolism would help to characterize this phenomenon with possible therapeutic implications. We analyzed mRNA expression of the key enzymes involved in aerobic glycolysis in normal mucosa (NM), primary tumor (PT) and liver metastasis (LM) of colorectal cancer (CRC) patients (pts) who underwent primary tumor surgery and liver metastasectomy. Tissues of 48 CRC pts were analyzed by RT-qPCR for mRNA expression of the following genes: hexokinase-1 (
HK-1
) and 2 (
HK-2
), embryonic pyruvate kinase (
PKM-2
), lactate dehydrogenase-A (
LDH-A
), glucose transporter-1 (
GLUT-1
), voltage-dependent anion-selective channel protein-1 (
VDAC-1
). Differences in the expression of the candidate genes between tissues and associations with clinical/pathologic features were studied.
GLUT-1
,
LDH-A
,
HK-1, PKM-2
and
VDAC-1
mRNA expression levels were significantly higher in PT/LM tissues compared with NM. There was a trend for higher expression of these genes in LM compared with PT tissues, but differences were statistically significant for
LDH-A
expression only.
RAS
mutation-positive disease was associated with high
GLUT-1
mRNA expression levels only. Right-sided colon tumors showed significantly higher
GLUT-1
,
PKM-2
and
LDH-A
mRNA expression levels. High glycolytic profile was significantly associated with poor prognosis in 20 metastatic,
RAS
-mutated pts treated with first-line chemotherapy plus Bevacizumab. Altered expression of effectors associated with upregulated glucose uptake and aerobic glycolysis occurs in CRC tissues. Additional analyses are warranted for addressing the role of these changes in anti-angiogenic resistance and for developing novel therapeutics.</description><subject>631/67/68</subject><subject>692/308/575</subject><subject>Aged</subject><subject>Analysis</subject><subject>Angiogenesis</subject><subject>Angiogenesis Inhibitors - therapeutic use</subject><subject>Antineoplastic Combined Chemotherapy Protocols - therapeutic use</subject><subject>Bevacizumab</subject><subject>Biomarkers, Tumor - genetics</subject><subject>Biomedical and Life Sciences</subject><subject>Biomedicine</subject><subject>Cancer</subject><subject>Care and treatment</subject><subject>Chemotherapy</subject><subject>Colectomy</subject><subject>Colorectal cancer</subject><subject>Colorectal carcinoma</subject><subject>Colorectal Neoplasms - enzymology</subject><subject>Colorectal Neoplasms - genetics</subject><subject>Colorectal Neoplasms - pathology</subject><subject>Colorectal Neoplasms - therapy</subject><subject>Development and progression</subject><subject>Disease Progression</subject><subject>Drug Resistance, Neoplasm - genetics</subject><subject>Embryos</subject><subject>Energy metabolism</subject><subject>Enzymes</subject><subject>Female</subject><subject>Gene Expression</subject><subject>Gene Expression Profiling</subject><subject>Gene Expression Regulation, Enzymologic</subject><subject>Gene Expression Regulation, Neoplastic</subject><subject>Genetic aspects</subject><subject>Genetic Predisposition to Disease</subject><subject>Glucose</subject><subject>Glucose metabolism</subject><subject>Glucose transporter</subject><subject>Glycolysis</subject><subject>Glycolysis - genetics</subject><subject>Health aspects</subject><subject>Hepatectomy</subject><subject>Hexokinase</subject><subject>Human Genetics</subject><subject>Humans</subject><subject>Identification and classification</subject><subject>Italy</subject><subject>Kaplan-Meier Estimate</subject><subject>Kinases</subject><subject>L-Lactate dehydrogenase</subject><subject>Lactic acid</subject><subject>Liver</subject><subject>Liver Neoplasms - enzymology</subject><subject>Liver Neoplasms - genetics</subject><subject>Liver Neoplasms - secondary</subject><subject>Liver Neoplasms - therapy</subject><subject>Male</subject><subject>Messenger RNA</subject><subject>Metabolism</subject><subject>Metastasectomy - methods</subject><subject>Metastases</subject><subject>Methods</subject><subject>Mucosa</subject><subject>Mutation</subject><subject>Oncology</subject><subject>original-article</subject><subject>Pharmacogenetics</subject><subject>Pharmacogenomic Variants</subject><subject>Pharmacotherapy</subject><subject>Phenotype</subject><subject>Polymerase chain reaction</subject><subject>Prognosis</subject><subject>Psychopharmacology</subject><subject>Pyruvate kinase</subject><subject>Pyruvic acid</subject><subject>Ras protein</subject><subject>Retrospective Studies</subject><subject>Risk Factors</subject><subject>RNA, Messenger - genetics</subject><subject>Statistical analysis</subject><subject>Time Factors</subject><subject>Treatment Outcome</subject><subject>Tumors</subject><issn>1470-269X</issn><issn>1473-1150</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2017</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>eNqNks9rFDEUxwdRbK2evEvAi6C75vcmx1JqFQpeFLyFN5k3a5bZZE1ml-5_b6bbapVSJYeEvM_7fpPHt2leMjpnVJj342Y155TpOROPmmMmF2LGmKKPr890xrX9dtQ8K2VFK8QW5mlzVO_4ght53Owuhr1Pw76EQpYYkeDVJmMpIUUCEQ4FiB0pOKAfww7JGkdo0xA8gW4HcYQlkhDJ-B2JH0IMHgayyWl5K5N6Uh1Sru214iF6zM-bJz0MBV_c7CfN1w_nX84-zi4_X3w6O72ceSXtONPC9K2xUoASHbTtoqUA2igrFdC-l6YzSIUURgLvAaWqiNRosaO9tFqKk-bNQbc-6McWy-jWoXgcBoiYtsUxS7XUjGnxb9RwrZXVnFb09V_oKm1znVZxXDOlBDVWPERVW2oEZYr_ppYwoAuxT2MGP1m7U20sr5-t6EOUtFxKodXkOL-HqqvDdfApYh_q_R-y_9Vw1-HtocHnVErG3m1yWEPeO0bdlEZX0-imNDo20a9uJrBt19j9Ym_jV4F3B6DUUlxivjOie_R-Amhe5os</recordid><startdate>20170601</startdate><enddate>20170601</enddate><creator>Graziano, F</creator><creator>Ruzzo, A</creator><creator>Giacomini, E</creator><creator>Ricciardi, T</creator><creator>Aprile, G</creator><creator>Loupakis, F</creator><creator>Lorenzini, P</creator><creator>Ongaro, E</creator><creator>Zoratto, F</creator><creator>Catalano, V</creator><creator>Sarti, D</creator><creator>Rulli, E</creator><creator>Cremolini, C</creator><creator>De Nictolis, M</creator><creator>De Maglio, G</creator><creator>Falcone, A</creator><creator>Fiorentini, G</creator><creator>Magnani, M</creator><general>Nature Publishing Group UK</general><general>Nature Publishing Group</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>3V.</scope><scope>7QP</scope><scope>7TK</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8FD</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</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>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>LK8</scope><scope>M0S</scope><scope>M1P</scope><scope>M7P</scope><scope>P64</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>RC3</scope><scope>7X8</scope></search><sort><creationdate>20170601</creationdate><title>Glycolysis gene expression analysis and selective metabolic advantage in the clinical progression of colorectal cancer</title><author>Graziano, F ; Ruzzo, A ; Giacomini, E ; Ricciardi, T ; Aprile, G ; Loupakis, F ; Lorenzini, P ; Ongaro, E ; Zoratto, F ; Catalano, V ; Sarti, D ; Rulli, E ; Cremolini, C ; De Nictolis, M ; De Maglio, G ; Falcone, A ; Fiorentini, G ; Magnani, M</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c549t-638fb8943a53dabb7b0aa685945a0ff48d8e034384a2fae45bb746e9ed0f49643</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2017</creationdate><topic>631/67/68</topic><topic>692/308/575</topic><topic>Aged</topic><topic>Analysis</topic><topic>Angiogenesis</topic><topic>Angiogenesis Inhibitors - therapeutic use</topic><topic>Antineoplastic Combined Chemotherapy Protocols - therapeutic use</topic><topic>Bevacizumab</topic><topic>Biomarkers, Tumor - genetics</topic><topic>Biomedical and Life Sciences</topic><topic>Biomedicine</topic><topic>Cancer</topic><topic>Care and treatment</topic><topic>Chemotherapy</topic><topic>Colectomy</topic><topic>Colorectal cancer</topic><topic>Colorectal carcinoma</topic><topic>Colorectal Neoplasms - enzymology</topic><topic>Colorectal Neoplasms - genetics</topic><topic>Colorectal Neoplasms - pathology</topic><topic>Colorectal Neoplasms - therapy</topic><topic>Development and progression</topic><topic>Disease Progression</topic><topic>Drug Resistance, Neoplasm - genetics</topic><topic>Embryos</topic><topic>Energy metabolism</topic><topic>Enzymes</topic><topic>Female</topic><topic>Gene Expression</topic><topic>Gene Expression Profiling</topic><topic>Gene Expression Regulation, Enzymologic</topic><topic>Gene Expression Regulation, Neoplastic</topic><topic>Genetic aspects</topic><topic>Genetic Predisposition to Disease</topic><topic>Glucose</topic><topic>Glucose metabolism</topic><topic>Glucose transporter</topic><topic>Glycolysis</topic><topic>Glycolysis - genetics</topic><topic>Health aspects</topic><topic>Hepatectomy</topic><topic>Hexokinase</topic><topic>Human Genetics</topic><topic>Humans</topic><topic>Identification and classification</topic><topic>Italy</topic><topic>Kaplan-Meier Estimate</topic><topic>Kinases</topic><topic>L-Lactate dehydrogenase</topic><topic>Lactic acid</topic><topic>Liver</topic><topic>Liver Neoplasms - enzymology</topic><topic>Liver Neoplasms - genetics</topic><topic>Liver Neoplasms - secondary</topic><topic>Liver Neoplasms - therapy</topic><topic>Male</topic><topic>Messenger RNA</topic><topic>Metabolism</topic><topic>Metastasectomy - methods</topic><topic>Metastases</topic><topic>Methods</topic><topic>Mucosa</topic><topic>Mutation</topic><topic>Oncology</topic><topic>original-article</topic><topic>Pharmacogenetics</topic><topic>Pharmacogenomic Variants</topic><topic>Pharmacotherapy</topic><topic>Phenotype</topic><topic>Polymerase chain reaction</topic><topic>Prognosis</topic><topic>Psychopharmacology</topic><topic>Pyruvate kinase</topic><topic>Pyruvic acid</topic><topic>Ras protein</topic><topic>Retrospective Studies</topic><topic>Risk Factors</topic><topic>RNA, Messenger - genetics</topic><topic>Statistical analysis</topic><topic>Time Factors</topic><topic>Treatment Outcome</topic><topic>Tumors</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Graziano, F</creatorcontrib><creatorcontrib>Ruzzo, A</creatorcontrib><creatorcontrib>Giacomini, E</creatorcontrib><creatorcontrib>Ricciardi, T</creatorcontrib><creatorcontrib>Aprile, G</creatorcontrib><creatorcontrib>Loupakis, F</creatorcontrib><creatorcontrib>Lorenzini, P</creatorcontrib><creatorcontrib>Ongaro, E</creatorcontrib><creatorcontrib>Zoratto, F</creatorcontrib><creatorcontrib>Catalano, V</creatorcontrib><creatorcontrib>Sarti, D</creatorcontrib><creatorcontrib>Rulli, E</creatorcontrib><creatorcontrib>Cremolini, C</creatorcontrib><creatorcontrib>De Nictolis, M</creatorcontrib><creatorcontrib>De Maglio, G</creatorcontrib><creatorcontrib>Falcone, A</creatorcontrib><creatorcontrib>Fiorentini, G</creatorcontrib><creatorcontrib>Magnani, M</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 Central (Corporate)</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>Neurosciences Abstracts</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>Technology Research 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 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>Engineering Research Database</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>ProQuest Biological Science Collection</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Biological Science Database</collection><collection>Biotechnology and BioEngineering Abstracts</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>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>The pharmacogenomics journal</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Graziano, F</au><au>Ruzzo, A</au><au>Giacomini, E</au><au>Ricciardi, T</au><au>Aprile, G</au><au>Loupakis, F</au><au>Lorenzini, P</au><au>Ongaro, E</au><au>Zoratto, F</au><au>Catalano, V</au><au>Sarti, D</au><au>Rulli, E</au><au>Cremolini, C</au><au>De Nictolis, M</au><au>De Maglio, G</au><au>Falcone, A</au><au>Fiorentini, G</au><au>Magnani, M</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Glycolysis gene expression analysis and selective metabolic advantage in the clinical progression of colorectal cancer</atitle><jtitle>The pharmacogenomics journal</jtitle><stitle>Pharmacogenomics J</stitle><addtitle>Pharmacogenomics J</addtitle><date>2017-06-01</date><risdate>2017</risdate><volume>17</volume><issue>3</issue><spage>258</spage><epage>264</epage><pages>258-264</pages><issn>1470-269X</issn><eissn>1473-1150</eissn><abstract>Production of lactate even in the presence of sufficient levels of oxygen (aerobic glycolysis) seems the prevalent energy metabolism pathway in cancer cells. The analysis of altered expression of effectors causing redirection of glucose metabolism would help to characterize this phenomenon with possible therapeutic implications. We analyzed mRNA expression of the key enzymes involved in aerobic glycolysis in normal mucosa (NM), primary tumor (PT) and liver metastasis (LM) of colorectal cancer (CRC) patients (pts) who underwent primary tumor surgery and liver metastasectomy. Tissues of 48 CRC pts were analyzed by RT-qPCR for mRNA expression of the following genes: hexokinase-1 (
HK-1
) and 2 (
HK-2
), embryonic pyruvate kinase (
PKM-2
), lactate dehydrogenase-A (
LDH-A
), glucose transporter-1 (
GLUT-1
), voltage-dependent anion-selective channel protein-1 (
VDAC-1
). Differences in the expression of the candidate genes between tissues and associations with clinical/pathologic features were studied.
GLUT-1
,
LDH-A
,
HK-1, PKM-2
and
VDAC-1
mRNA expression levels were significantly higher in PT/LM tissues compared with NM. There was a trend for higher expression of these genes in LM compared with PT tissues, but differences were statistically significant for
LDH-A
expression only.
RAS
mutation-positive disease was associated with high
GLUT-1
mRNA expression levels only. Right-sided colon tumors showed significantly higher
GLUT-1
,
PKM-2
and
LDH-A
mRNA expression levels. High glycolytic profile was significantly associated with poor prognosis in 20 metastatic,
RAS
-mutated pts treated with first-line chemotherapy plus Bevacizumab. Altered expression of effectors associated with upregulated glucose uptake and aerobic glycolysis occurs in CRC tissues. Additional analyses are warranted for addressing the role of these changes in anti-angiogenic resistance and for developing novel therapeutics.</abstract><cop>London</cop><pub>Nature Publishing Group UK</pub><pmid>26927284</pmid><doi>10.1038/tpj.2016.13</doi><tpages>7</tpages></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1470-269X |
| ispartof | The pharmacogenomics journal, 2017-06, Vol.17 (3), p.258-264 |
| issn | 1470-269X 1473-1150 |
| language | eng |
| recordid | cdi_proquest_miscellaneous_1906461163 |
| source | MEDLINE; Alma/SFX Local Collection |
| subjects | 631/67/68 692/308/575 Aged Analysis Angiogenesis Angiogenesis Inhibitors - therapeutic use Antineoplastic Combined Chemotherapy Protocols - therapeutic use Bevacizumab Biomarkers, Tumor - genetics Biomedical and Life Sciences Biomedicine Cancer Care and treatment Chemotherapy Colectomy Colorectal cancer Colorectal carcinoma Colorectal Neoplasms - enzymology Colorectal Neoplasms - genetics Colorectal Neoplasms - pathology Colorectal Neoplasms - therapy Development and progression Disease Progression Drug Resistance, Neoplasm - genetics Embryos Energy metabolism Enzymes Female Gene Expression Gene Expression Profiling Gene Expression Regulation, Enzymologic Gene Expression Regulation, Neoplastic Genetic aspects Genetic Predisposition to Disease Glucose Glucose metabolism Glucose transporter Glycolysis Glycolysis - genetics Health aspects Hepatectomy Hexokinase Human Genetics Humans Identification and classification Italy Kaplan-Meier Estimate Kinases L-Lactate dehydrogenase Lactic acid Liver Liver Neoplasms - enzymology Liver Neoplasms - genetics Liver Neoplasms - secondary Liver Neoplasms - therapy Male Messenger RNA Metabolism Metastasectomy - methods Metastases Methods Mucosa Mutation Oncology original-article Pharmacogenetics Pharmacogenomic Variants Pharmacotherapy Phenotype Polymerase chain reaction Prognosis Psychopharmacology Pyruvate kinase Pyruvic acid Ras protein Retrospective Studies Risk Factors RNA, Messenger - genetics Statistical analysis Time Factors Treatment Outcome Tumors |
| title | Glycolysis gene expression analysis and selective metabolic advantage in the clinical progression of colorectal cancer |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-19T16%3A11%3A20IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-gale_proqu&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Glycolysis%20gene%20expression%20analysis%20and%20selective%20metabolic%20advantage%20in%20the%20clinical%20progression%20of%20colorectal%20cancer&rft.jtitle=The%20pharmacogenomics%20journal&rft.au=Graziano,%20F&rft.date=2017-06-01&rft.volume=17&rft.issue=3&rft.spage=258&rft.epage=264&rft.pages=258-264&rft.issn=1470-269X&rft.eissn=1473-1150&rft_id=info:doi/10.1038/tpj.2016.13&rft_dat=%3Cgale_proqu%3EA689285908%3C/gale_proqu%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=1900830152&rft_id=info:pmid/26927284&rft_galeid=A689285908&rfr_iscdi=true |