The Biological and Clinical Significance of Glutaminase in Luminal Breast Cancer

The Biological and Clinical Significance of Glutaminase in Luminal Breast Cancer | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Help Center Sign In Submit a Preprint Cite Share Download PDF Research The Biological and Clinical Significance of Glutaminase in Luminal Breast Cancer Brendah Masisi, Rokaya El-Ansari, Lutfi Alfarsi, Madeleine Craze, and 6 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-93938/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 06 Aug, 2021 Read the published version in Cancers → Version 1 posted You are reading this latest preprint version Abstract Background : Glutamine metabolism has a key role in the regulation of uncontrolled tumour growth by modulating bioenergetics, redox homeostasis and serving as a precursor for biomass synthesis. Glutaminase is a key enzyme involved in glutaminolysis, a process which plays a crucial role in carcinogenesis and progression. This study aimed to evaluate the expression and prognostic significance of glutaminase in luminal breast cancer (BC). Methods : The glutaminase protein isoforms (GLS and GLS2) were assessed at the genomic and transcriptomic levels, using METABRIC (n=1398) and GENE MINER datasets (n=4,712), and protein level using immunohistochemistry in large well characterised cohorts of luminal Oestrogen Receptor (ER)-positive and HER2-negative BC patients, including ductal carcinoma in situ (DCIS) (n=206) and invasive BC (IBC; n=717) cohorts. GLS and GLS2 expression was associated with clinicopathological features, patient outcome and other glutamine-metabolism related genes. Results : In DCIS, GLS expression was an independent risk factor for shorter local recurrence-free interval (p<0.0008). In IBC high GLS and GLS2 mRNA and protein expression significantly correlated with solute carriers with high glutamine affinity, SLC3A2 (p≤0.01) SLC7A8 (p≤0.01) and SLC7A5 (p<0.001), and glutamine related enzymes; GLUD1 (p<0.001) and ALDH18A1 (p<0.001). GLS and GLS2 gene copy number gains were associated with poor patient outcome (p=0.028; p=0.010 respectively). High GLS2 protein was predictive of a longer disease-free survival (p=0.006). Conclusion : GLS appears to play a role in the early non-invasive stage of BC and it could be used as a potential biomarker to predict DCIS progression to invasive disease. In IBC, both GLS and GLS2 play a key role in the biological function of luminal tumours. Further functional assessments are needed to explore the specific role played by each isoform in BC. Cancer Biology Glutaminase DCIS IBC prognosis Figures Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 Figure 7 Full Text Tables Due to technical limitations, table 1,2,3,4,5,6 is only available as a download in the Supplemental Files section. Supplementary Files Table1.JPG Table2.JPG Table3.JPG Table4.JPG Table5.JPG Table6.JPG Cite Share Download PDF Status: Published Journal Publication published 06 Aug, 2021 Read the published version in Cancers → Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-93938","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research","associatedPublications":[],"authors":[{"id":3700025,"identity":"f59a934c-ac92-4cce-a87d-146c3b1ce84c","order_by":0,"name":"Brendah Masisi","email":"","orcid":"","institution":"University of Nottingham University Park Campus: University of Nottingham","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Brendah","middleName":"","lastName":"Masisi","suffix":""},{"id":3700026,"identity":"244b3ff1-2d33-44ed-84b5-848780e748ec","order_by":1,"name":"Rokaya El-Ansari","email":"","orcid":"","institution":"University of Nottingham","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Rokaya","middleName":"","lastName":"El-Ansari","suffix":""},{"id":3700027,"identity":"cd2b2f49-edef-4b95-b57b-87a691f6f529","order_by":2,"name":"Lutfi Alfarsi","email":"","orcid":"","institution":"University of Nottingham","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Lutfi","middleName":"","lastName":"Alfarsi","suffix":""},{"id":3700028,"identity":"b43be108-d576-4d55-a288-3d93e6ba97da","order_by":3,"name":"Madeleine Craze","email":"","orcid":"","institution":"University of Nottingham","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Madeleine","middleName":"","lastName":"Craze","suffix":""},{"id":3700029,"identity":"2fbc07f9-926f-45b0-b5dd-616e7a136f4c","order_by":4,"name":"Natasha Jewa","email":"","orcid":"","institution":"University of Nottingham","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Natasha","middleName":"","lastName":"Jewa","suffix":""},{"id":3700030,"identity":"5d0d3f8d-de3f-42f5-9297-b436793994b7","order_by":5,"name":"Andrew Oldfield","email":"","orcid":"","institution":"University of Nottingham","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Andrew","middleName":"","lastName":"Oldfield","suffix":""},{"id":3700031,"identity":"9b04e0f2-3c16-4a62-9de0-d5044ae828e3","order_by":6,"name":"Hayley Cheung","email":"","orcid":"","institution":"University of Nottingham","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Hayley","middleName":"","lastName":"Cheung","suffix":""},{"id":3700032,"identity":"e1d23dbe-f3eb-4556-a5d3-576c4ae13adb","order_by":7,"name":"Michael Toss","email":"","orcid":"","institution":"University of Nottingham","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Michael","middleName":"","lastName":"Toss","suffix":""},{"id":3700033,"identity":"41670e76-6e16-4985-ad5d-92b6418f5a39","order_by":8,"name":"Emad Rakha","email":"","orcid":"","institution":"University of Nottingham","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Emad","middleName":"","lastName":"Rakha","suffix":""},{"id":3700034,"identity":"639a46bc-5207-4558-84c6-035e1aec812c","order_by":9,"name":"Andrew Green","email":"data:image/png;base64,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","orcid":"https://orcid.org/0000-0002-0488-5913","institution":"University of Nottingham","correspondingAuthor":true,"submittingAuthor":false,"prefix":"","firstName":"Andrew","middleName":"","lastName":"Green","suffix":""}],"badges":[],"createdAt":"2020-10-16 19:20:00","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-93938/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-93938/v1","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.3390/cancers13163963","type":"published","date":"2021-08-06T20:29:47+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":3157422,"identity":"e1016813-217d-47ba-81d5-a5d8d316aee5","added_by":"auto","created_at":"2020-10-23 15:05:43","extension":"jpg","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":89988,"visible":true,"origin":"","legend":"GLS and GLS2 protein expression in ER+/HER2- DCIS and invasive breast\ncancer. Representative TMA images (x20 magnification) depicting (A) negative\nimmunostaining, positive GLS (B) and GLS2 (C) immunostaining in DCIS cases. (D)\nNegative immunostaining, positive GLS (E) and GLS2 (F) expression in invasive breast\ntumours.","description":"","filename":"Fig1.JPG","url":"https://assets-eu.researchsquare.com/files/rs-93938/v1/7d31fc8325187edbe75e897b.JPG"},{"id":3157424,"identity":"3ccfabb8-27af-4f6a-82c3-880d37036abd","added_by":"auto","created_at":"2020-10-23 15:05:43","extension":"jpg","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":42632,"visible":true,"origin":"","legend":"Glutaminase protein expression and its association with clinicopathological\nparameters and molecular subtypes in ER+/HER2- DCIS: a GLS and GLS2, GLS and b\ntumour size, d tumour grade, f comedo type necrosis, h luminal subtypes; GLS2 and c\ntumour size, e tumour grade, g comedo type necrosis, i luminal subtypes.","description":"","filename":"Fig2.JPG","url":"https://assets-eu.researchsquare.com/files/rs-93938/v1/abb25016a54435befc02d242.JPG"},{"id":3157426,"identity":"cca86708-c415-41ce-ab10-a8dae4ac541c","added_by":"auto","created_at":"2020-10-23 15:05:43","extension":"jpg","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":74055,"visible":true,"origin":"","legend":"Correlation between glutaminase mRNA and protein expression in ER+/HER2-\ninvasive breast cancer: GLS and GLS2 mRNA in a all tumours, c luminal A tumours, e\nluminal B tumours; GLS and GLS2 protein in b all tumours, d low proliferation tumours, f\nhigh proliferation tumours. Copy number gain and relationship with mRNA expression for g\nGLS, h GLS2.","description":"","filename":"Fig3.JPG","url":"https://assets-eu.researchsquare.com/files/rs-93938/v1/faa67d45efb296ce1b8cabbd.JPG"},{"id":3157428,"identity":"5f628e50-24f2-477a-ba2e-0c172e0de611","added_by":"auto","created_at":"2020-10-23 15:05:43","extension":"jpg","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":48916,"visible":true,"origin":"","legend":"Glutaminase mRNA expression and its association with clinicopathological\nparameters: GLS and a tumour size, c tumour grade, e lymph node stage, g luminal subtypes,\ni METABRIC integrative clusters; GLS2 and b tumour size, d tumour grade, f lymph node\nstage, h luminal subtypes, j METABRIC integrative clusters.","description":"","filename":"Fig4.JPG","url":"https://assets-eu.researchsquare.com/files/rs-93938/v1/56ec26c08e103cf46e5af413.JPG"},{"id":3157430,"identity":"9b03124b-a350-49f2-85a6-918bf3565296","added_by":"auto","created_at":"2020-10-23 15:05:44","extension":"jpg","order_by":5,"title":"Figure 5","display":"","copyAsset":false,"role":"figure","size":58123,"visible":true,"origin":"","legend":"Glutaminase protein expression and its association with clinicopathological\nparameters and molecular subtypes in ER+/HER2- invasive breast cancer: GLS and a tumour size, c, tumour grade, e lymph node stage, g luminal subtypes; GLS2 and b tumour size, d tumour grade, f lymph node stage, h luminal subtypes.","description":"","filename":"Fig5.JPG","url":"https://assets-eu.researchsquare.com/files/rs-93938/v1/a8662344cb68e0cb5ed494fc.JPG"},{"id":3157432,"identity":"5472711e-c97f-495e-91bf-a6f0cb1ded8f","added_by":"auto","created_at":"2020-10-23 15:05:44","extension":"jpg","order_by":6,"title":"Figure 6","display":"","copyAsset":false,"role":"figure","size":39842,"visible":true,"origin":"","legend":"Association of GLS and GLS2 protein expression with tumour recurrence in\nER+/HER2- DCIS: a GLS, b GLS2 and, c combined expression of GLS and GLS2.","description":"","filename":"Fig6.JPG","url":"https://assets-eu.researchsquare.com/files/rs-93938/v1/c08234bcfa9a48808e71354f.JPG"},{"id":3157433,"identity":"423ee919-722f-4d52-ba4e-46be4cd56fe9","added_by":"auto","created_at":"2020-10-23 15:05:44","extension":"jpg","order_by":7,"title":"Figure 7","display":"","copyAsset":false,"role":"figure","size":47858,"visible":true,"origin":"","legend":"Association of glutaminase expression with patient outcome in ER+/HER2-\ninvasive breast cancer in the METABRIC and Nottingham series: breast cancer specific\nsurvival of a GLS copy number gain, b GLS2 copy number gain, c GLS mRNA, d GLS2\nmRNA, e GLS protein and f GLS2 protein, disease free interval of g GLS protein, h GLS2\nprotein, i combined expression of GLS and GLS2.","description":"","filename":"Fig7.JPG","url":"https://assets-eu.researchsquare.com/files/rs-93938/v1/80f3d323df8ade130d46d201.JPG"},{"id":13545830,"identity":"fbc9f436-d3f3-46ee-a789-56a6f4c8d9a4","added_by":"auto","created_at":"2021-09-17 02:07:38","extension":"pdf","order_by":1,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":685035,"visible":true,"origin":"","legend":"","description":"","filename":"GLSandGLS2inDCISandIBCFINALVERSIONER.pdf","url":"https://assets-eu.researchsquare.com/files/rs-93938/v1_covered.pdf"},{"id":3157439,"identity":"ab945c51-9cff-4d62-a74d-f1618ca854ef","added_by":"auto","created_at":"2020-10-23 15:05:47","extension":"pdf","order_by":1,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":261882,"visible":true,"origin":"","legend":"","description":"","filename":"GLSandGLS2inDCISandIBCFINALVERSIONER.pdf","url":"https://assets-eu.researchsquare.com/files/rs-93938/v1_stamped.pdf"},{"id":3157421,"identity":"f587055f-f542-4742-8bf4-e6bc1c0c57e4","added_by":"auto","created_at":"2020-10-23 15:05:42","extension":"jpg","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":123160,"visible":true,"origin":"","legend":"","description":"","filename":"Table1.JPG","url":"https://assets-eu.researchsquare.com/files/rs-93938/v1/0830c68060d142423e11ab39.JPG"},{"id":3157423,"identity":"6907eb77-443a-486b-bed2-05f6de584507","added_by":"auto","created_at":"2020-10-23 15:05:43","extension":"jpg","order_by":2,"title":"","display":"","copyAsset":false,"role":"supplement","size":120282,"visible":true,"origin":"","legend":"","description":"","filename":"Table2.JPG","url":"https://assets-eu.researchsquare.com/files/rs-93938/v1/f08e526cdc4366e00a5c848e.JPG"},{"id":3157425,"identity":"ff548caf-9573-46d5-8c51-e084beccfd59","added_by":"auto","created_at":"2020-10-23 15:05:43","extension":"jpg","order_by":3,"title":"","display":"","copyAsset":false,"role":"supplement","size":85655,"visible":true,"origin":"","legend":"","description":"","filename":"Table3.JPG","url":"https://assets-eu.researchsquare.com/files/rs-93938/v1/13165c0bc7111622821fbc99.JPG"},{"id":3157427,"identity":"ba528aaa-87be-47de-9687-85d74bbf8c66","added_by":"auto","created_at":"2020-10-23 15:05:43","extension":"jpg","order_by":4,"title":"","display":"","copyAsset":false,"role":"supplement","size":79499,"visible":true,"origin":"","legend":"","description":"","filename":"Table4.JPG","url":"https://assets-eu.researchsquare.com/files/rs-93938/v1/878d9b6ea2c77b43ea651fb3.JPG"},{"id":3157429,"identity":"7d45a444-9378-42c7-a8fd-3e958c2c2a48","added_by":"auto","created_at":"2020-10-23 15:05:44","extension":"jpg","order_by":5,"title":"","display":"","copyAsset":false,"role":"supplement","size":34911,"visible":true,"origin":"","legend":"","description":"","filename":"Table5.JPG","url":"https://assets-eu.researchsquare.com/files/rs-93938/v1/72b76b8270b96c596a94d121.JPG"},{"id":3157431,"identity":"e85d7b33-214b-498c-98f7-5b19df7ab78d","added_by":"auto","created_at":"2020-10-23 15:05:44","extension":"jpg","order_by":6,"title":"","display":"","copyAsset":false,"role":"supplement","size":31964,"visible":true,"origin":"","legend":"","description":"","filename":"Table6.JPG","url":"https://assets-eu.researchsquare.com/files/rs-93938/v1/e8c0520b092053ed8a66cbac.JPG"}],"financialInterests":"","formattedTitle":"\u003cp\u003eThe Biological and Clinical Significance of Glutaminase in Luminal Breast Cancer\u003c/p\u003e","fulltext":[{"header":"Full Text","content":"\u003cp\u003eThis preprint is available for \u003ca href='/article/rs-93938/latest.pdf' target='_blank'\u003edownload as a PDF\u003c/a\u003e.\u003c/p\u003e"},{"header":"Tables","content":"\u003cp\u003eDue to technical limitations, table 1,2,3,4,5,6 is only available as a download in the Supplemental Files section.\u003c/p\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":false,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":true,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"Glutaminase, DCIS, IBC, prognosis","lastPublishedDoi":"10.21203/rs.3.rs-93938/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-93938/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eBackground\u003c/strong\u003e: Glutamine metabolism has a key role in the regulation of uncontrolled tumour growth by modulating bioenergetics, redox homeostasis and serving as a precursor for biomass synthesis. Glutaminase is a key enzyme involved in glutaminolysis, a process which plays a crucial role in carcinogenesis and progression. This study aimed to evaluate the expression and prognostic significance of glutaminase in luminal breast cancer (BC). \u003c/p\u003e\u003cp\u003e\u003cstrong\u003eMethods\u003c/strong\u003e: The glutaminase protein isoforms (GLS and GLS2) were assessed at the genomic and transcriptomic levels, using METABRIC (n=1398) and GENE MINER datasets (n=4,712), and protein level using immunohistochemistry in large well characterised cohorts of luminal Oestrogen Receptor (ER)-positive and HER2-negative BC patients, including ductal carcinoma in situ (DCIS) (n=206) and invasive BC (IBC; n=717) cohorts. GLS and GLS2 expression was associated with clinicopathological features, patient outcome and other glutamine-metabolism related genes. \u003c/p\u003e\u003cp\u003e\u003cstrong\u003eResults\u003c/strong\u003e: In DCIS, GLS expression was an independent risk factor for shorter local recurrence-free interval (p\u0026lt;0.0008). In IBC high GLS and GLS2 mRNA and protein expression significantly correlated with solute carriers with high glutamine affinity, SLC3A2 (p≤0.01) SLC7A8 (p≤0.01) and SLC7A5 (p\u0026lt;0.001), and glutamine related enzymes; GLUD1 (p\u0026lt;0.001) and ALDH18A1 (p\u0026lt;0.001). GLS and GLS2 gene copy number gains were associated with poor patient outcome (p=0.028; p=0.010 respectively). High GLS2 protein was predictive of a longer disease-free survival (p=0.006). \u003c/p\u003e\u003cp\u003e\u003cstrong\u003eConclusion\u003c/strong\u003e: GLS appears to play a role in the early non-invasive stage of BC and it could be used as a potential biomarker to predict DCIS progression to invasive disease. In IBC, both GLS and GLS2 play a key role in the biological function of luminal tumours. Further functional assessments are needed to explore the specific role played by each isoform in BC.\u003c/p\u003e","manuscriptTitle":"The Biological and Clinical Significance of Glutaminase in Luminal Breast Cancer","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2020-10-23 15:05:40","doi":"10.21203/rs.3.rs-93938/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"18a3e42e-d075-4ed1-8bef-e7c14e6f7405","owner":[],"postedDate":"October 23rd, 2020","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[{"id":851251,"name":"Cancer Biology"}],"tags":[],"updatedAt":"2024-07-16T20:29:47+00:00","versionOfRecord":{"articleIdentity":"rs-93938","link":"https://doi.org/10.3390/cancers13163963","journal":{"identity":"cancers","isVorOnly":true,"title":"Cancers"},"publishedOn":"2021-08-06 20:29:47","publishedOnDateReadable":"August 6th, 2021"},"versionCreatedAt":"2020-10-23 15:05:40","video":"","vorDoi":"10.3390/cancers13163963","vorDoiUrl":"https://doi.org/10.3390/cancers13163963","workflowStages":[]},"version":"v1","identity":"rs-93938","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-93938","identity":"rs-93938","version":["v1"]},"buildId":"omnImTCwR2MFx8CMYfrG7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}