Association between phosphorylated AMP-activated protein kinase and acetyl-CoA carboxylase expression and outcome in patients with squamous cell carcinoma of the head and neck
Epidemiological studies have indicated that impaired glucose metabolism may increase the risk of squamous cell carcinoma of the head and neck (SCCHN). AMP-activated protein kinase (AMPK) regulates glucose and lipid metabolism via the phosphorylation and subsequent inactivation of its downstream targ...
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| Veröffentlicht in: | PloS one 2014-04, Vol.9 (4), p.e96183-e96183 |
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| creator | Su, Ying-Wen Lin, Yun-Ho Pai, Man-Hui Lo, An-Chi Lee, Yu-Chieh Fang, I-Chih Lin, Johnson Hsieh, Ruey-Kuen Chang, Yi-Fang Chen, Chi-Long |
| description | Epidemiological studies have indicated that impaired glucose metabolism may increase the risk of squamous cell carcinoma of the head and neck (SCCHN). AMP-activated protein kinase (AMPK) regulates glucose and lipid metabolism via the phosphorylation and subsequent inactivation of its downstream target acetyl-CoA carboxylase (ACC).Thus, we analyzed the expression of pAMPK and its downstream target phosphorylated acetyl-CoA carboxylase (pACC), as well as their impact on the survival of patients with resected SCCHN.
One hundred eighteen patients with surgically resected SCCHN were enrolled. Immunohistochemical (IHC) staining for pAMPK and pACC was performed using tissue microarrays of operative specimens of SCCHN. The expression was divided into two or three groups according to the IHC score [pAMPK: negative (0), positive (1-3); pACC: negative (0), low expression (1, 2), and high expression (3)]. Statistical analysis was performed to determine the association of pAMPK expression with clinicopathological features and pACC and pErk expression.
The positive rates of pAMPK and pACC expression were 64.4% (76/118) and 68.6% (81/118), respectively. pAMPK was significantly higher in patients aged younger than 60 years (P = 0.024; χ2 test) and those with early-stage (T1/T2; P = 0.02; χ2 test) and oral cavity (P = 0.026; Fisher's exact test) tumors. In multivariate analysis, pAMPK expression was not significantly correlated with overall survival (OS) (adjusted hazard ratio [HR]: 0.66; 95% confidence interval [CI]: 0.35-1.23), whereas high pACC expression was independently associated with worse OS in node-positive patients (adjusted HR: 17.58; 95% CI: 3.50-88.18).
Strong expression of pACC was found to be an independent prognostic marker for patients with node-positive SCCHN. Our results suggest that pACC may play a role in tumor progression of SCCHN and may help to identify patient subgroups at high risk for poor disease outcome. |
| doi_str_mv | 10.1371/journal.pone.0096183 |
| format | Article |
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One hundred eighteen patients with surgically resected SCCHN were enrolled. Immunohistochemical (IHC) staining for pAMPK and pACC was performed using tissue microarrays of operative specimens of SCCHN. The expression was divided into two or three groups according to the IHC score [pAMPK: negative (0), positive (1-3); pACC: negative (0), low expression (1, 2), and high expression (3)]. Statistical analysis was performed to determine the association of pAMPK expression with clinicopathological features and pACC and pErk expression.
The positive rates of pAMPK and pACC expression were 64.4% (76/118) and 68.6% (81/118), respectively. pAMPK was significantly higher in patients aged younger than 60 years (P = 0.024; χ2 test) and those with early-stage (T1/T2; P = 0.02; χ2 test) and oral cavity (P = 0.026; Fisher's exact test) tumors. In multivariate analysis, pAMPK expression was not significantly correlated with overall survival (OS) (adjusted hazard ratio [HR]: 0.66; 95% confidence interval [CI]: 0.35-1.23), whereas high pACC expression was independently associated with worse OS in node-positive patients (adjusted HR: 17.58; 95% CI: 3.50-88.18).
Strong expression of pACC was found to be an independent prognostic marker for patients with node-positive SCCHN. Our results suggest that pACC may play a role in tumor progression of SCCHN and may help to identify patient subgroups at high risk for poor disease outcome.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0096183</identifier><identifier>PMID: 24769813</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Acetyl-CoA carboxylase ; Acetyl-CoA Carboxylase - metabolism ; Adenylate Kinase - metabolism ; Adult ; Aged ; Aged, 80 and over ; AMP ; AMP-activated protein kinase ; Analysis ; Apoptosis ; Biomarkers, Tumor - metabolism ; Breast cancer ; Carcinoma, Squamous Cell - enzymology ; Carcinoma, Squamous Cell - mortality ; Carcinoma, Squamous Cell - secondary ; Carcinoma, Squamous Cell - therapy ; Care and treatment ; Cell growth ; Confidence intervals ; Deactivation ; Development and progression ; Diagnosis ; Epidemiology ; Extracellular Signal-Regulated MAP Kinases - metabolism ; Fatty acids ; Female ; Glucose ; Glucose kinase ; Glucose metabolism ; Head & neck cancer ; Head and Neck Neoplasms - enzymology ; Head and Neck Neoplasms - mortality ; Head and Neck Neoplasms - pathology ; Head and Neck Neoplasms - therapy ; Health risks ; Hematology ; Hospitals ; Humans ; Inactivation ; Internal medicine ; Kaplan-Meier Estimate ; Kinases ; Lipid metabolism ; Lymphatic Metastasis ; Male ; Medicine ; Medicine and Health Sciences ; Metabolism ; Middle Aged ; Multivariate Analysis ; Neck ; Neoadjuvant Therapy ; Oncology ; Oral cavity ; Pathology ; Patient outcomes ; Patients ; Phosphoproteins - metabolism ; Phosphorylation ; Prognosis ; Proportional Hazards Models ; Protein kinases ; Protein Processing, Post-Translational ; Proteins ; Squamous cell carcinoma ; Statistical analysis ; Studies ; Subgroups ; Survival ; Tissue Array Analysis ; Treatment Outcome ; Tumors</subject><ispartof>PloS one, 2014-04, Vol.9 (4), p.e96183-e96183</ispartof><rights>COPYRIGHT 2014 Public Library of Science</rights><rights>2014 Su et?al. This is an open-access article distributed under the terms of the Creative Commons Attribution License: http://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2014 Su et?al 2014 Su et?al</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c692t-683edb05ec9f7823591adb80a199351453ba4f38b36935004c859f7df45ef8603</citedby><cites>FETCH-LOGICAL-c692t-683edb05ec9f7823591adb80a199351453ba4f38b36935004c859f7df45ef8603</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/PMC4000216/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4000216/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,860,881,2096,2915,23845,27901,27902,53766,53768,79343,79344</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/24769813$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><contributor>Singh, Pankaj K.</contributor><creatorcontrib>Su, Ying-Wen</creatorcontrib><creatorcontrib>Lin, Yun-Ho</creatorcontrib><creatorcontrib>Pai, Man-Hui</creatorcontrib><creatorcontrib>Lo, An-Chi</creatorcontrib><creatorcontrib>Lee, Yu-Chieh</creatorcontrib><creatorcontrib>Fang, I-Chih</creatorcontrib><creatorcontrib>Lin, Johnson</creatorcontrib><creatorcontrib>Hsieh, Ruey-Kuen</creatorcontrib><creatorcontrib>Chang, Yi-Fang</creatorcontrib><creatorcontrib>Chen, Chi-Long</creatorcontrib><title>Association between phosphorylated AMP-activated protein kinase and acetyl-CoA carboxylase expression and outcome in patients with squamous cell carcinoma of the head and neck</title><title>PloS one</title><addtitle>PLoS One</addtitle><description>Epidemiological studies have indicated that impaired glucose metabolism may increase the risk of squamous cell carcinoma of the head and neck (SCCHN). AMP-activated protein kinase (AMPK) regulates glucose and lipid metabolism via the phosphorylation and subsequent inactivation of its downstream target acetyl-CoA carboxylase (ACC).Thus, we analyzed the expression of pAMPK and its downstream target phosphorylated acetyl-CoA carboxylase (pACC), as well as their impact on the survival of patients with resected SCCHN.
One hundred eighteen patients with surgically resected SCCHN were enrolled. Immunohistochemical (IHC) staining for pAMPK and pACC was performed using tissue microarrays of operative specimens of SCCHN. The expression was divided into two or three groups according to the IHC score [pAMPK: negative (0), positive (1-3); pACC: negative (0), low expression (1, 2), and high expression (3)]. Statistical analysis was performed to determine the association of pAMPK expression with clinicopathological features and pACC and pErk expression.
The positive rates of pAMPK and pACC expression were 64.4% (76/118) and 68.6% (81/118), respectively. pAMPK was significantly higher in patients aged younger than 60 years (P = 0.024; χ2 test) and those with early-stage (T1/T2; P = 0.02; χ2 test) and oral cavity (P = 0.026; Fisher's exact test) tumors. In multivariate analysis, pAMPK expression was not significantly correlated with overall survival (OS) (adjusted hazard ratio [HR]: 0.66; 95% confidence interval [CI]: 0.35-1.23), whereas high pACC expression was independently associated with worse OS in node-positive patients (adjusted HR: 17.58; 95% CI: 3.50-88.18).
Strong expression of pACC was found to be an independent prognostic marker for patients with node-positive SCCHN. Our results suggest that pACC may play a role in tumor progression of SCCHN and may help to identify patient subgroups at high risk for poor disease outcome.</description><subject>Acetyl-CoA carboxylase</subject><subject>Acetyl-CoA Carboxylase - metabolism</subject><subject>Adenylate Kinase - metabolism</subject><subject>Adult</subject><subject>Aged</subject><subject>Aged, 80 and over</subject><subject>AMP</subject><subject>AMP-activated protein kinase</subject><subject>Analysis</subject><subject>Apoptosis</subject><subject>Biomarkers, Tumor - metabolism</subject><subject>Breast cancer</subject><subject>Carcinoma, Squamous Cell - enzymology</subject><subject>Carcinoma, Squamous Cell - mortality</subject><subject>Carcinoma, Squamous Cell - secondary</subject><subject>Carcinoma, Squamous Cell - therapy</subject><subject>Care and treatment</subject><subject>Cell growth</subject><subject>Confidence intervals</subject><subject>Deactivation</subject><subject>Development and progression</subject><subject>Diagnosis</subject><subject>Epidemiology</subject><subject>Extracellular Signal-Regulated MAP Kinases - metabolism</subject><subject>Fatty acids</subject><subject>Female</subject><subject>Glucose</subject><subject>Glucose kinase</subject><subject>Glucose metabolism</subject><subject>Head & neck cancer</subject><subject>Head and Neck Neoplasms - enzymology</subject><subject>Head and Neck Neoplasms - mortality</subject><subject>Head and Neck Neoplasms - pathology</subject><subject>Head and Neck Neoplasms - therapy</subject><subject>Health risks</subject><subject>Hematology</subject><subject>Hospitals</subject><subject>Humans</subject><subject>Inactivation</subject><subject>Internal medicine</subject><subject>Kaplan-Meier Estimate</subject><subject>Kinases</subject><subject>Lipid metabolism</subject><subject>Lymphatic Metastasis</subject><subject>Male</subject><subject>Medicine</subject><subject>Medicine and Health Sciences</subject><subject>Metabolism</subject><subject>Middle Aged</subject><subject>Multivariate Analysis</subject><subject>Neck</subject><subject>Neoadjuvant Therapy</subject><subject>Oncology</subject><subject>Oral cavity</subject><subject>Pathology</subject><subject>Patient outcomes</subject><subject>Patients</subject><subject>Phosphoproteins - metabolism</subject><subject>Phosphorylation</subject><subject>Prognosis</subject><subject>Proportional Hazards Models</subject><subject>Protein kinases</subject><subject>Protein Processing, Post-Translational</subject><subject>Proteins</subject><subject>Squamous cell carcinoma</subject><subject>Statistical analysis</subject><subject>Studies</subject><subject>Subgroups</subject><subject>Survival</subject><subject>Tissue Array Analysis</subject><subject>Treatment Outcome</subject><subject>Tumors</subject><issn>1932-6203</issn><issn>1932-6203</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2014</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>BENPR</sourceid><sourceid>DOA</sourceid><recordid>eNqNk9tu1DAQhiMEoqXwBggsISG4yGLHiZPcVFqtOFQqKuJ0azn2ZNfbxE5tp90-Fa-Is91WXdQLZEXx4fv_iSczSfKS4BmhJfmwtqMzopsN1sAM45qRij5KDklNs5RlmD6-Nz9Innm_xrigFWNPk4MsL1ldEXqY_Jl7b6UWQVuDGghXAAYNK-vj4647EUCh-ddvqZBBX25Xg7MBtEHn2ggPSBiFhIRw3aULO0dSuMZuojAewWZw4P3kPFF2DNL2gKJ2iPHABI-udFghfzGK3o4eSei6yUFqY3uBbIvCCtAKhNoaGJDnz5Mnreg8vNi9j5Jfnz7-XHxJT88-nyzmp6lkdRZSVlFQDS5A1m1ZZbSoiVBNhQWpa1qQvKCNyFtaNZTFNca5rIpIqjYvoK0YpkfJ6xvfobOe73LtOSlIjYuS5VkkTm4IZcWaD073wl1zKzTfbli35MIFLTvgClMhZK3yMg6WkZpAllHWtrRU0CoavY530camByVjbpzo9kz3T4xe8aW95DnGOCMsGrzbGTh7MYIPvNd-SqcwEDO7_e4qzypGIvrmH_Th2-2opYgX0Ka1Ma6cTPmclkVRFVmdR2r2ABWHgl7LWJitjvt7gvd7gsgE2ISlGL3nJz--_z979nuffXuPjRXThZW33TiVtd8H8xtQOuu9g_YuyQTzqa9us8GnvuK7voqyV_d_0J3otpHoX66qIG8</recordid><startdate>20140401</startdate><enddate>20140401</enddate><creator>Su, Ying-Wen</creator><creator>Lin, Yun-Ho</creator><creator>Pai, Man-Hui</creator><creator>Lo, An-Chi</creator><creator>Lee, Yu-Chieh</creator><creator>Fang, I-Chih</creator><creator>Lin, Johnson</creator><creator>Hsieh, Ruey-Kuen</creator><creator>Chang, Yi-Fang</creator><creator>Chen, Chi-Long</creator><general>Public Library of Science</general><general>Public Library of Science (PLoS)</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>IOV</scope><scope>ISR</scope><scope>3V.</scope><scope>7QG</scope><scope>7QL</scope><scope>7QO</scope><scope>7RV</scope><scope>7SN</scope><scope>7SS</scope><scope>7T5</scope><scope>7TG</scope><scope>7TM</scope><scope>7U9</scope><scope>7X2</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8FD</scope><scope>8FE</scope><scope>8FG</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABJCF</scope><scope>ABUWG</scope><scope>AEUYN</scope><scope>AFKRA</scope><scope>ARAPS</scope><scope>ATCPS</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BGLVJ</scope><scope>BHPHI</scope><scope>C1K</scope><scope>CCPQU</scope><scope>D1I</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>KB.</scope><scope>KB0</scope><scope>KL.</scope><scope>L6V</scope><scope>LK8</scope><scope>M0K</scope><scope>M0S</scope><scope>M1P</scope><scope>M7N</scope><scope>M7P</scope><scope>M7S</scope><scope>NAPCQ</scope><scope>P5Z</scope><scope>P62</scope><scope>P64</scope><scope>PATMY</scope><scope>PDBOC</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PTHSS</scope><scope>PYCSY</scope><scope>RC3</scope><scope>7X8</scope><scope>5PM</scope><scope>DOA</scope></search><sort><creationdate>20140401</creationdate><title>Association between phosphorylated AMP-activated protein kinase and acetyl-CoA carboxylase expression and outcome in patients with squamous cell carcinoma of the head and neck</title><author>Su, Ying-Wen ; Lin, Yun-Ho ; Pai, Man-Hui ; Lo, An-Chi ; Lee, Yu-Chieh ; Fang, I-Chih ; Lin, Johnson ; Hsieh, Ruey-Kuen ; Chang, Yi-Fang ; Chen, Chi-Long</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c692t-683edb05ec9f7823591adb80a199351453ba4f38b36935004c859f7df45ef8603</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2014</creationdate><topic>Acetyl-CoA carboxylase</topic><topic>Acetyl-CoA Carboxylase - metabolism</topic><topic>Adenylate Kinase - metabolism</topic><topic>Adult</topic><topic>Aged</topic><topic>Aged, 80 and over</topic><topic>AMP</topic><topic>AMP-activated protein kinase</topic><topic>Analysis</topic><topic>Apoptosis</topic><topic>Biomarkers, Tumor - metabolism</topic><topic>Breast cancer</topic><topic>Carcinoma, Squamous Cell - enzymology</topic><topic>Carcinoma, Squamous Cell - mortality</topic><topic>Carcinoma, Squamous Cell - secondary</topic><topic>Carcinoma, Squamous Cell - therapy</topic><topic>Care and treatment</topic><topic>Cell growth</topic><topic>Confidence intervals</topic><topic>Deactivation</topic><topic>Development and progression</topic><topic>Diagnosis</topic><topic>Epidemiology</topic><topic>Extracellular Signal-Regulated MAP Kinases - metabolism</topic><topic>Fatty acids</topic><topic>Female</topic><topic>Glucose</topic><topic>Glucose kinase</topic><topic>Glucose metabolism</topic><topic>Head & neck cancer</topic><topic>Head and Neck Neoplasms - enzymology</topic><topic>Head and Neck Neoplasms - mortality</topic><topic>Head and Neck Neoplasms - pathology</topic><topic>Head and Neck Neoplasms - therapy</topic><topic>Health risks</topic><topic>Hematology</topic><topic>Hospitals</topic><topic>Humans</topic><topic>Inactivation</topic><topic>Internal medicine</topic><topic>Kaplan-Meier Estimate</topic><topic>Kinases</topic><topic>Lipid metabolism</topic><topic>Lymphatic Metastasis</topic><topic>Male</topic><topic>Medicine</topic><topic>Medicine and Health Sciences</topic><topic>Metabolism</topic><topic>Middle Aged</topic><topic>Multivariate Analysis</topic><topic>Neck</topic><topic>Neoadjuvant Therapy</topic><topic>Oncology</topic><topic>Oral cavity</topic><topic>Pathology</topic><topic>Patient outcomes</topic><topic>Patients</topic><topic>Phosphoproteins - metabolism</topic><topic>Phosphorylation</topic><topic>Prognosis</topic><topic>Proportional Hazards Models</topic><topic>Protein kinases</topic><topic>Protein Processing, Post-Translational</topic><topic>Proteins</topic><topic>Squamous cell carcinoma</topic><topic>Statistical analysis</topic><topic>Studies</topic><topic>Subgroups</topic><topic>Survival</topic><topic>Tissue Array Analysis</topic><topic>Treatment Outcome</topic><topic>Tumors</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Su, Ying-Wen</creatorcontrib><creatorcontrib>Lin, Yun-Ho</creatorcontrib><creatorcontrib>Pai, Man-Hui</creatorcontrib><creatorcontrib>Lo, An-Chi</creatorcontrib><creatorcontrib>Lee, Yu-Chieh</creatorcontrib><creatorcontrib>Fang, I-Chih</creatorcontrib><creatorcontrib>Lin, Johnson</creatorcontrib><creatorcontrib>Hsieh, Ruey-Kuen</creatorcontrib><creatorcontrib>Chang, Yi-Fang</creatorcontrib><creatorcontrib>Chen, Chi-Long</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Opposing Viewpoints in Context (Gale)</collection><collection>Gale In Context: Science</collection><collection>ProQuest Central (Corporate)</collection><collection>Animal Behavior Abstracts</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Biotechnology Research Abstracts</collection><collection>Proquest Nursing & Allied Health Source</collection><collection>Ecology Abstracts</collection><collection>Entomology Abstracts (Full archive)</collection><collection>Immunology Abstracts</collection><collection>Meteorological & Geoastrophysical Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Agricultural Science Collection</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>Public Health Database</collection><collection>Technology Research Database</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Technology 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>Materials Science & Engineering Collection</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest One Sustainability</collection><collection>ProQuest Central UK/Ireland</collection><collection>Advanced Technologies & Aerospace Collection</collection><collection>Agricultural & Environmental Science Collection</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Technology Collection</collection><collection>Natural Science Collection</collection><collection>Environmental Sciences and Pollution Management</collection><collection>ProQuest One Community College</collection><collection>ProQuest Materials Science Collection</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>AIDS and Cancer Research Abstracts</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Materials Science Database</collection><collection>Nursing & Allied Health Database (Alumni Edition)</collection><collection>Meteorological & Geoastrophysical Abstracts - 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Academic</collection><collection>PubMed Central (Full Participant titles)</collection><collection>DOAJ Directory of Open Access Journals</collection><jtitle>PloS one</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Su, Ying-Wen</au><au>Lin, Yun-Ho</au><au>Pai, Man-Hui</au><au>Lo, An-Chi</au><au>Lee, Yu-Chieh</au><au>Fang, I-Chih</au><au>Lin, Johnson</au><au>Hsieh, Ruey-Kuen</au><au>Chang, Yi-Fang</au><au>Chen, Chi-Long</au><au>Singh, Pankaj K.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Association between phosphorylated AMP-activated protein kinase and acetyl-CoA carboxylase expression and outcome in patients with squamous cell carcinoma of the head and neck</atitle><jtitle>PloS one</jtitle><addtitle>PLoS One</addtitle><date>2014-04-01</date><risdate>2014</risdate><volume>9</volume><issue>4</issue><spage>e96183</spage><epage>e96183</epage><pages>e96183-e96183</pages><issn>1932-6203</issn><eissn>1932-6203</eissn><abstract>Epidemiological studies have indicated that impaired glucose metabolism may increase the risk of squamous cell carcinoma of the head and neck (SCCHN). AMP-activated protein kinase (AMPK) regulates glucose and lipid metabolism via the phosphorylation and subsequent inactivation of its downstream target acetyl-CoA carboxylase (ACC).Thus, we analyzed the expression of pAMPK and its downstream target phosphorylated acetyl-CoA carboxylase (pACC), as well as their impact on the survival of patients with resected SCCHN.
One hundred eighteen patients with surgically resected SCCHN were enrolled. Immunohistochemical (IHC) staining for pAMPK and pACC was performed using tissue microarrays of operative specimens of SCCHN. The expression was divided into two or three groups according to the IHC score [pAMPK: negative (0), positive (1-3); pACC: negative (0), low expression (1, 2), and high expression (3)]. Statistical analysis was performed to determine the association of pAMPK expression with clinicopathological features and pACC and pErk expression.
The positive rates of pAMPK and pACC expression were 64.4% (76/118) and 68.6% (81/118), respectively. pAMPK was significantly higher in patients aged younger than 60 years (P = 0.024; χ2 test) and those with early-stage (T1/T2; P = 0.02; χ2 test) and oral cavity (P = 0.026; Fisher's exact test) tumors. In multivariate analysis, pAMPK expression was not significantly correlated with overall survival (OS) (adjusted hazard ratio [HR]: 0.66; 95% confidence interval [CI]: 0.35-1.23), whereas high pACC expression was independently associated with worse OS in node-positive patients (adjusted HR: 17.58; 95% CI: 3.50-88.18).
Strong expression of pACC was found to be an independent prognostic marker for patients with node-positive SCCHN. Our results suggest that pACC may play a role in tumor progression of SCCHN and may help to identify patient subgroups at high risk for poor disease outcome.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>24769813</pmid><doi>10.1371/journal.pone.0096183</doi><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1932-6203 |
| ispartof | PloS one, 2014-04, Vol.9 (4), p.e96183-e96183 |
| issn | 1932-6203 1932-6203 |
| language | eng |
| recordid | cdi_plos_journals_1519057642 |
| source | MEDLINE; DOAJ Directory of Open Access Journals; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; PubMed Central; Free Full-Text Journals in Chemistry; Public Library of Science (PLoS) |
| subjects | Acetyl-CoA carboxylase Acetyl-CoA Carboxylase - metabolism Adenylate Kinase - metabolism Adult Aged Aged, 80 and over AMP AMP-activated protein kinase Analysis Apoptosis Biomarkers, Tumor - metabolism Breast cancer Carcinoma, Squamous Cell - enzymology Carcinoma, Squamous Cell - mortality Carcinoma, Squamous Cell - secondary Carcinoma, Squamous Cell - therapy Care and treatment Cell growth Confidence intervals Deactivation Development and progression Diagnosis Epidemiology Extracellular Signal-Regulated MAP Kinases - metabolism Fatty acids Female Glucose Glucose kinase Glucose metabolism Head & neck cancer Head and Neck Neoplasms - enzymology Head and Neck Neoplasms - mortality Head and Neck Neoplasms - pathology Head and Neck Neoplasms - therapy Health risks Hematology Hospitals Humans Inactivation Internal medicine Kaplan-Meier Estimate Kinases Lipid metabolism Lymphatic Metastasis Male Medicine Medicine and Health Sciences Metabolism Middle Aged Multivariate Analysis Neck Neoadjuvant Therapy Oncology Oral cavity Pathology Patient outcomes Patients Phosphoproteins - metabolism Phosphorylation Prognosis Proportional Hazards Models Protein kinases Protein Processing, Post-Translational Proteins Squamous cell carcinoma Statistical analysis Studies Subgroups Survival Tissue Array Analysis Treatment Outcome Tumors |
| title | Association between phosphorylated AMP-activated protein kinase and acetyl-CoA carboxylase expression and outcome in patients with squamous cell carcinoma of the head and neck |
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