{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T19:50:27Z","timestamp":1791921027684,"version":"4.3.4"},"reference-count":48,"publisher":"Wiley","license":[{"start":{"date-parts":[[2021,1,5]],"date-time":"2021-01-05T00:00:00Z","timestamp":1609804800000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100008005","name":"Yonsei University College of Medicine","doi-asserted-by":"publisher","award":["6-2016-0163"],"award-info":[{"award-number":["6-2016-0163"]}],"id":[{"id":"10.13039\/501100008005","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Disease Markers"],"published-print":{"date-parts":[[2021,1,5]]},"abstract":"<jats:p>Background. Glutamine metabolism is considered an important metabolic phenotype of proliferating tumor cells. Objective. The objective of this study was to investigate the expression of glutamine metabolism-related and amino acid transporter proteins in adrenal cortical neoplasms (ACNs) and pheochromocytomas (PCCs) in the adrenal gland. Methods. A tissue microarray was constructed for 132 cases of ACN (115 cases of adrenal cortical adenoma and 17 cases of adrenal cortical carcinoma) and 189 cases of PCC. Immunohistochemical staining for glutamine metabolism-related proteins GLS1 and GDH and amino acid transporter proteins SLC1A5, SLC7A5, and SLC7A11 as well as SDHB was performed and compared with clinicopathologic parameters. Results. The expression levels of GLS (<jats:inline-formula>\n                     <a:math xmlns:a=\"http:\/\/www.w3.org\/1998\/Math\/MathML\" id=\"M1\">\n                        <a:mi>p<\/a:mi>\n                        <a:mo>&lt;<\/a:mo>\n                        <a:mn>0.001<\/a:mn>\n                     <\/a:math>\n                  <\/jats:inline-formula>), SLC7A5 (<jats:inline-formula>\n                     <c:math xmlns:c=\"http:\/\/www.w3.org\/1998\/Math\/MathML\" id=\"M2\">\n                        <c:mi>p<\/c:mi>\n                        <c:mo>=<\/c:mo>\n                        <c:mn>0.049<\/c:mn>\n                     <\/c:math>\n                  <\/jats:inline-formula>), and SDHB (<jats:inline-formula>\n                     <e:math xmlns:e=\"http:\/\/www.w3.org\/1998\/Math\/MathML\" id=\"M3\">\n                        <e:mi>p<\/e:mi>\n                        <e:mo>=<\/e:mo>\n                        <e:mn>0.007<\/e:mn>\n                     <\/e:math>\n                  <\/jats:inline-formula>) were higher in ACN than in PCC, whereas the expression levels of SLC1A5 (<jats:inline-formula>\n                     <g:math xmlns:g=\"http:\/\/www.w3.org\/1998\/Math\/MathML\" id=\"M4\">\n                        <g:mi>p<\/g:mi>\n                        <g:mo>&lt;<\/g:mo>\n                        <g:mn>0.001<\/g:mn>\n                     <\/g:math>\n                  <\/jats:inline-formula>) and SLC7A11 (<jats:inline-formula>\n                     <i:math xmlns:i=\"http:\/\/www.w3.org\/1998\/Math\/MathML\" id=\"M5\">\n                        <i:mi>p<\/i:mi>\n                        <i:mo>&lt;<\/i:mo>\n                        <i:mn>0.001<\/i:mn>\n                     <\/i:math>\n                  <\/jats:inline-formula>) were higher in PCC than in ACN. In ACN, GLS positivity was associated with a higher Fuhrman grade (<jats:inline-formula>\n                     <k:math xmlns:k=\"http:\/\/www.w3.org\/1998\/Math\/MathML\" id=\"M6\">\n                        <k:mi>p<\/k:mi>\n                        <k:mo>=<\/k:mo>\n                        <k:mn>0.009<\/k:mn>\n                     <\/k:math>\n                  <\/jats:inline-formula>), and SLC1A5 positivity was associated with SDHB positivity (<jats:inline-formula>\n                     <m:math xmlns:m=\"http:\/\/www.w3.org\/1998\/Math\/MathML\" id=\"M7\">\n                        <m:mi>p<\/m:mi>\n                        <m:mo>=<\/m:mo>\n                        <m:mn>0.004<\/m:mn>\n                     <\/m:math>\n                  <\/jats:inline-formula>) and a clear cell <jats:inline-formula>\n                     <o:math xmlns:o=\"http:\/\/www.w3.org\/1998\/Math\/MathML\" id=\"M8\">\n                        <o:mtext>proportion<\/o:mtext>\n                        <o:mo>&lt;<\/o:mo>\n                        <o:mn>25<\/o:mn>\n                        <o:mi>%<\/o:mi>\n                     <\/o:math>\n                  <\/jats:inline-formula> (<jats:inline-formula>\n                     <q:math xmlns:q=\"http:\/\/www.w3.org\/1998\/Math\/MathML\" id=\"M9\">\n                        <q:mi>p<\/q:mi>\n                        <q:mo>=<\/q:mo>\n                        <q:mn>0.010<\/q:mn>\n                     <\/q:math>\n                  <\/jats:inline-formula>). SDHB negativity was also associated with tumor cell necrosis (<jats:inline-formula>\n                     <s:math xmlns:s=\"http:\/\/www.w3.org\/1998\/Math\/MathML\" id=\"M10\">\n                        <s:mi>p<\/s:mi>\n                        <s:mo>=<\/s:mo>\n                        <s:mn>0.007<\/s:mn>\n                     <\/s:math>\n                  <\/jats:inline-formula>). In PCC, SLC7A11 positivity was associated with nonnorepinephrine type (<jats:inline-formula>\n                     <u:math xmlns:u=\"http:\/\/www.w3.org\/1998\/Math\/MathML\" id=\"M11\">\n                        <u:mi>p<\/u:mi>\n                        <u:mo>=<\/u:mo>\n                        <u:mn>0.008<\/u:mn>\n                     <\/u:math>\n                  <\/jats:inline-formula>). In Kaplan-Meier analysis, patients with GLS positivity (<jats:inline-formula>\n                     <w:math xmlns:w=\"http:\/\/www.w3.org\/1998\/Math\/MathML\" id=\"M12\">\n                        <w:mi>p<\/w:mi>\n                        <w:mo>=<\/w:mo>\n                        <w:mn>0.039<\/w:mn>\n                     <\/w:math>\n                  <\/jats:inline-formula>) and SDHB negativity (<jats:inline-formula>\n                     <y:math xmlns:y=\"http:\/\/www.w3.org\/1998\/Math\/MathML\" id=\"M13\">\n                        <y:mi>p<\/y:mi>\n                        <y:mo>=<\/y:mo>\n                        <y:mn>0.005<\/y:mn>\n                     <\/y:math>\n                  <\/jats:inline-formula>) had significantly shorter overall survival in ACN. In PCC patients with a <jats:inline-formula>\n                     <ab:math xmlns:ab=\"http:\/\/www.w3.org\/1998\/Math\/MathML\" id=\"M14\">\n                        <ab:mtext>GAPP<\/ab:mtext>\n                        <ab:mtext>\u2009<\/ab:mtext>\n                        <ab:mtext>score<\/ab:mtext>\n                        <ab:mo>\u2265<\/ab:mo>\n                        <ab:mn>3<\/ab:mn>\n                     <\/ab:math>\n                  <\/jats:inline-formula>, GLS positivity (<jats:inline-formula>\n                     <cb:math xmlns:cb=\"http:\/\/www.w3.org\/1998\/Math\/MathML\" id=\"M15\">\n                        <cb:mi>p<\/cb:mi>\n                        <cb:mo>=<\/cb:mo>\n                        <cb:mn>0.001<\/cb:mn>\n                     <\/cb:math>\n                  <\/jats:inline-formula>) and SDHB positivity (<jats:inline-formula>\n                     <eb:math xmlns:eb=\"http:\/\/www.w3.org\/1998\/Math\/MathML\" id=\"M16\">\n                        <eb:mi>p<\/eb:mi>\n                        <eb:mo>=<\/eb:mo>\n                        <eb:mn>0.001<\/eb:mn>\n                     <\/eb:math>\n                  <\/jats:inline-formula>) were associated with shorter disease-free survival, whereas GLS positivity (<jats:inline-formula>\n                     <gb:math xmlns:gb=\"http:\/\/www.w3.org\/1998\/Math\/MathML\" id=\"M17\">\n                        <gb:mi>p<\/gb:mi>\n                        <gb:mo>=<\/gb:mo>\n                        <gb:mn>0.004<\/gb:mn>\n                     <\/gb:math>\n                  <\/jats:inline-formula>) was also associated with shorter overall survival. Conclusions. The expression of glutamine metabolism-related and amino acid transporter proteins in ACN and PCC is distinct and associated with prognosis.<\/jats:p>","DOI":"10.1155\/2021\/8850990","type":"journal-article","created":{"date-parts":[[2021,1,6]],"date-time":"2021-01-06T23:06:19Z","timestamp":1609974379000},"page":"1-9","source":"Crossref","is-referenced-by-count":9,"title":["Expression of Glutamine Metabolism-Related and Amino Acid Transporter Proteins in Adrenal Cortical Neoplasms and Pheochromocytomas"],"prefix":"10.1155","volume":"2021","author":[{"given":"Hye Min","family":"Kim","sequence":"first","affiliation":[{"name":"Department of Pathology, Yonsei University College of Medicine, Seoul, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4546-4709","authenticated-orcid":true,"given":"Ja Seung","family":"Koo","sequence":"additional","affiliation":[{"name":"Department of Pathology, Yonsei University College of Medicine, Seoul, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","reference":[{"key":"1","doi-asserted-by":"publisher","DOI":"10.1007\/s11912-019-0773-7"},{"key":"2","doi-asserted-by":"publisher","DOI":"10.1016\/j.mce.2013.10.028"},{"key":"3","doi-asserted-by":"publisher","DOI":"10.1016\/s0140-6736(05)67139-5"},{"key":"4","doi-asserted-by":"publisher","DOI":"10.1016\/j.trecan.2017.01.005"},{"key":"5","doi-asserted-by":"publisher","DOI":"10.4062\/biomolther.2017.178"},{"key":"6","doi-asserted-by":"publisher","DOI":"10.1038\/nature10602"},{"key":"7","doi-asserted-by":"publisher","DOI":"10.1111\/j.1471-4159.1990.tb08831.x"},{"key":"8","doi-asserted-by":"publisher","DOI":"10.1038\/onc.2009.358"},{"key":"9","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.Can-14-3745"},{"key":"10","doi-asserted-by":"publisher","DOI":"10.1097\/mco.0000000000000430"},{"key":"11","doi-asserted-by":"publisher","DOI":"10.15252\/embj.201696151"},{"key":"12","doi-asserted-by":"publisher","DOI":"10.1016\/j.tibs.2010.05.003"},{"key":"13","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.Can-09-3556"},{"key":"14","doi-asserted-by":"publisher","DOI":"10.1016\/b978-0-12-394316-3.00001-6"},{"key":"15","doi-asserted-by":"publisher","DOI":"10.1042\/bj20101912"},{"key":"16","doi-asserted-by":"publisher","DOI":"10.1016\/j.pharmthera.2008.09.005"},{"key":"17","doi-asserted-by":"publisher","DOI":"10.1097\/00000478-198403000-00001"},{"key":"18","doi-asserted-by":"publisher","DOI":"10.1097\/00000478-198903000-00004"},{"key":"19","doi-asserted-by":"publisher","DOI":"10.1530\/erc-13-0494"},{"key":"20","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.Ccr-06-1746"},{"key":"21","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2265.2008.03257.x"},{"key":"22","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0156044"},{"key":"23","doi-asserted-by":"publisher","DOI":"10.1007\/s00259-016-3586-z"},{"key":"24","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.Ccr-16-0606"},{"key":"25","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccr.2013.04.018"},{"key":"26","doi-asserted-by":"publisher","DOI":"10.1093\/jnci\/djt201"},{"key":"27","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms3139"},{"key":"28","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.Ccr-14-2804"},{"key":"29","doi-asserted-by":"publisher","DOI":"10.3389\/fonc.2019.00053"},{"key":"30","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2796.2009.02111.x"},{"key":"31","doi-asserted-by":"publisher","DOI":"10.3390\/jcm7090242"},{"key":"32","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2018-01968"},{"key":"33","doi-asserted-by":"publisher","DOI":"10.1158\/1535-7163.Mct-13-0870"},{"key":"34","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2015-01-621870"},{"key":"35","doi-asserted-by":"publisher","DOI":"10.3109\/14756366.2011.622272"},{"key":"36","doi-asserted-by":"publisher","DOI":"10.1172\/jci75836"},{"key":"37","doi-asserted-by":"publisher","DOI":"10.1016\/j.exphem.2013.12.001"},{"key":"38","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.208"},{"key":"39","doi-asserted-by":"publisher","DOI":"10.1021\/mp500405h"},{"key":"40","doi-asserted-by":"publisher","DOI":"10.4161\/epi.22713"},{"key":"41","doi-asserted-by":"publisher","DOI":"10.1016\/j.tem.2013.01.002"},{"key":"42","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.RA117.001342"},{"issue":"4","key":"43","first-page":"1281","article-title":"L-type amino acid transport and cancer: targeting the mTORC1 pathway to inhibit neoplasia","volume":"5","author":"Q. 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