{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T11:55:16Z","timestamp":1789127716519,"version":"build-2803163510"},"reference-count":34,"publisher":"MDPI AG","issue":"16","license":[{"start":{"date-parts":[[2021,8,6]],"date-time":"2021-08-06T00:00:00Z","timestamp":1628208000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>The glutamine metabolism has a key role in the regulation of uncontrolled tumour growth. This study aimed to evaluate the expression and prognostic significance of glutaminase in luminal breast cancer (BC). The glutaminase isoforms (GLS\/GLS2) were assessed at genomic\/transcriptomic levels, using METABRIC (n = 1398) and GeneMiner datasets (n = 4712), and protein using immunohistochemistry in well-characterised cohorts of Oestrogen receptor-positive\/HER2-negative BC patients: ductal carcinoma in situ (DCIS; n = 206) and invasive breast cancer (IBC; n = 717). Glutaminase expression was associated with clinicopathological features, patient outcome and glutamine-metabolism-related genes. In DCIS, GLS alone and GLS+\/GLS2- expression were risk factors for shorter local recurrence-free interval (p &lt; 0.0001 and p = 0.001, respectively) and remained prognostic factors independent of tumour size, grade and comedo necrosis (p = 0.0008 and p = 0.003, respectively). In IBC, GLS gene copy number gain with high mRNA expression was associated with poor patient outcome (p = 0.011), whereas high GLS2 protein was predictive of a longer disease-free survival (p = 0.006). Glutaminase plays a role in the biological function of luminal BC, particularly GLS in the early non-invasive stage, which could be used as a potential biomarker to predict disease progression and a target for inhibition. Further validation is required to confirm these observations, and functional assessments are needed to explore their specific roles.<\/jats:p>","DOI":"10.3390\/cancers13163963","type":"journal-article","created":{"date-parts":[[2021,8,6]],"date-time":"2021-08-06T05:22:01Z","timestamp":1628227321000},"page":"3963","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":25,"title":["The Biological and Clinical Significance of Glutaminase in Luminal Breast Cancer"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0974-5397","authenticated-orcid":false,"given":"Brendah K.","family":"Masisi","sequence":"first","affiliation":[{"name":"Nottingham Breast Cancer Research Centre, Academic Unit for Translational Medical Sciences, School of Medicine, University of Nottingham Biodiscovery Institute, University Park, Nottingham NG7 2RD, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rokaya","family":"El Ansari","sequence":"additional","affiliation":[{"name":"Nottingham Breast Cancer Research Centre, Academic Unit for Translational Medical Sciences, School of Medicine, University of Nottingham Biodiscovery Institute, University Park, Nottingham NG7 2RD, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lutfi","family":"Alfarsi","sequence":"additional","affiliation":[{"name":"Nottingham Breast Cancer Research Centre, Academic Unit for Translational Medical Sciences, School of Medicine, University of Nottingham Biodiscovery Institute, University Park, Nottingham NG7 2RD, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Madeleine L.","family":"Craze","sequence":"additional","affiliation":[{"name":"Nottingham Breast Cancer Research Centre, Academic Unit for Translational Medical Sciences, School of Medicine, University of Nottingham Biodiscovery Institute, University Park, Nottingham NG7 2RD, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Natasha","family":"Jewa","sequence":"additional","affiliation":[{"name":"Nottingham Breast Cancer Research Centre, Academic Unit for Translational Medical Sciences, School of Medicine, University of Nottingham Biodiscovery Institute, University Park, Nottingham NG7 2RD, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew","family":"Oldfield","sequence":"additional","affiliation":[{"name":"Nottingham Breast Cancer Research Centre, Academic Unit for Translational Medical Sciences, School of Medicine, University of Nottingham Biodiscovery Institute, University Park, Nottingham NG7 2RD, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hayley","family":"Cheung","sequence":"additional","affiliation":[{"name":"Nottingham Breast Cancer Research Centre, Academic Unit for Translational Medical Sciences, School of Medicine, University of Nottingham Biodiscovery Institute, University Park, Nottingham NG7 2RD, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Toss","sequence":"additional","affiliation":[{"name":"Nottingham Breast Cancer Research Centre, Academic Unit for Translational Medical Sciences, School of Medicine, University of Nottingham Biodiscovery Institute, University Park, Nottingham NG7 2RD, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emad A.","family":"Rakha","sequence":"additional","affiliation":[{"name":"Nottingham Breast Cancer Research Centre, Academic Unit for Translational Medical Sciences, School of Medicine, University of Nottingham Biodiscovery Institute, University Park, Nottingham NG7 2RD, UK"},{"name":"Cellular Pathology, Nottingham University Hospitals NHS Trust, Hucknall Road, Nottingham NG5 1PB, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0488-5913","authenticated-orcid":false,"given":"Andrew R.","family":"Green","sequence":"additional","affiliation":[{"name":"Nottingham Breast Cancer Research Centre, Academic Unit for Translational Medical Sciences, School of Medicine, University of Nottingham Biodiscovery Institute, University Park, Nottingham NG7 2RD, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,8,6]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"646","DOI":"10.1016\/j.cell.2011.02.013","article-title":"Hallmarks of Cancer: The Next Generation","volume":"144","author":"Hanahan","year":"2011","journal-title":"Cell"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"427","DOI":"10.1016\/j.tibs.2010.05.003","article-title":"Glutamine addiction: A new therapeutic target in cancer","volume":"35","author":"Wise","year":"2010","journal-title":"Trends Biochem. 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