{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,25]],"date-time":"2026-02-25T11:09:43Z","timestamp":1772017783389,"version":"3.50.1"},"reference-count":34,"publisher":"MDPI AG","issue":"20","license":[{"start":{"date-parts":[[2023,10,11]],"date-time":"2023-10-11T00:00:00Z","timestamp":1696982400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Liga Portuguesa Contra o Cancro (LPCC) and Ausonia (2021)","award":["SFRH\/BD\/146489\/2019"],"award-info":[{"award-number":["SFRH\/BD\/146489\/2019"]}]},{"DOI":"10.13039\/501100001871","name":"Funda\u00e7\u00e3o para a Ci\u00eancia e Tecnologia","doi-asserted-by":"publisher","award":["SFRH\/BD\/146489\/2019"],"award-info":[{"award-number":["SFRH\/BD\/146489\/2019"]}],"id":[{"id":"10.13039\/501100001871","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Breast cancer is a heterogeneous entity, where different molecular subtypes (MS) exhibit distinct prognostic and therapeutic responses. A series of 62 breast cancer samples stratified by MS was obtained from the tumor biobank of IPO-Porto. The expression of glycolysis and gluconeogenesis-regulating enzymes was investigated by immunohistochemistry. Data analysis included stratification according to MS, body mass index (BMI), and BMI with MS (mBMI). We observed significant differences in pyruvate carboxylase (PC), phosphoenolpyruvate carboxykinase (PCK), and fructose-1,6-bisphosphatase (FBP) tumor cell expression when stratified by MS and mBMI. The expression of these enzymes was also statistically dependent on hormonal receptors and HER2 status and correlated with pathological stage and histological grade. Obesity tended to attenuate these differences, particularly in PC expression, although these were not affected by adipocyte deposition or inflammatory infiltration at the tumor microenvironment. Nonetheless, PCK and FBP expression was also modified by the presence of obesity-associated disorders like diabetes, hypertension, and dyslipidemia. Taken together, these findings identify metabolic fingerprints for breast cancer as distinct histological types, which are affected by the presence of obesity and obesity-associated conditions. Despite the biological role of the differential expression of enzymes remaining unknown, the current study highlights the need to identify the expression of gluconeogenic-regulating enzymes as a tool for personalized medicine.<\/jats:p>","DOI":"10.3390\/cancers15204936","type":"journal-article","created":{"date-parts":[[2023,10,11]],"date-time":"2023-10-11T08:18:57Z","timestamp":1697012337000},"page":"4936","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Breast Cancer Molecular Subtypes Differentially Express Gluconeogenic Rate-Limiting Enzymes\u2014Obesity as a Crucial Player"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5292-6337","authenticated-orcid":false,"given":"Carla","family":"Lu\u00eds","sequence":"first","affiliation":[{"name":"Biochemistry Unit, Department of Biomedicine, Faculty of Medicine, University of Porto (FMUP), Al. Prof. Hern\u00e2ni Monteiro, 4200-319 Porto, Portugal"},{"name":"i3S\u2014Instituto de Inova\u00e7\u00e3o e Investiga\u00e7\u00e3o em Sa\u00fade, University of Porto, 4200-135 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1006-6946","authenticated-orcid":false,"given":"Fernando","family":"Schmitt","sequence":"additional","affiliation":[{"name":"Institute of Molecular Pathology and Immunology of the University of Porto (IPATIMUP), 4200-135 Porto, Portugal"},{"name":"Pathology and Oncology Unit, Pathological Anatomy Laboratory, Faculty of Medicine, University of Porto (FMUP), Al. Prof. Hern\u00e2ni Monteiro, 4200-319 Porto, Portugal"},{"name":"CINTESIS@RISE, Health Research Network, 4200-319 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5534-050X","authenticated-orcid":false,"given":"Rute","family":"Fernandes","sequence":"additional","affiliation":[{"name":"Portuguese Oncology Institute of Porto, 4200-072 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7809-6597","authenticated-orcid":false,"given":"Nuno","family":"Coimbra","sequence":"additional","affiliation":[{"name":"Portuguese Oncology Institute of Porto, 4200-072 Porto, Portugal"},{"name":"Cancer Biology & Epigenetics Group, Research Center of IPO Porto (CI-IPOP)\/RISE@CI-IPOP (Health Research Network), Portuguese Oncology Institute of Porto (IPO-Porto)\/Porto Comprehensive Cancer Center Raquel Seruca (Porto.CCC), 4200-072 Porto, Portugal"},{"name":"Department of Pathology and Molecular Immunology, School of Medicine & Biomedical Sciences, University of Porto (ICBAS-UP), 4050-313 Porto, Portugal"}]},{"given":"Joana","family":"Rigor","sequence":"additional","affiliation":[{"name":"Biochemistry Unit, Department of Biomedicine, Faculty of Medicine, University of Porto (FMUP), Al. Prof. Hern\u00e2ni Monteiro, 4200-319 Porto, Portugal"},{"name":"Internal Medicine Department, P\u00f3voa de Varzim\/Vila do Conde Hospital Centre, 4490-421 P\u00f3voa de Varzim, Portugal"}]},{"given":"Paula","family":"Dias","sequence":"additional","affiliation":[{"name":"Cancer Biology & Epigenetics Group, Research Center of IPO Porto (CI-IPOP)\/RISE@CI-IPOP (Health Research Network), Portuguese Oncology Institute of Porto (IPO-Porto)\/Porto Comprehensive Cancer Center Raquel Seruca (Porto.CCC), 4200-072 Porto, Portugal"}]},{"given":"Dina","family":"Leit\u00e3o","sequence":"additional","affiliation":[{"name":"Pathology and Oncology Unit, Pathological Anatomy Laboratory, Faculty of Medicine, University of Porto (FMUP), Al. Prof. Hern\u00e2ni Monteiro, 4200-319 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8933-3984","authenticated-orcid":false,"given":"R\u00faben","family":"Fernandes","sequence":"additional","affiliation":[{"name":"i3S\u2014Instituto de Inova\u00e7\u00e3o e Investiga\u00e7\u00e3o em Sa\u00fade, University of Porto, 4200-135 Porto, Portugal"},{"name":"FP-I3ID\u2014Instituto de Investiga\u00e7\u00e3o, Inova\u00e7\u00e3o e Desenvolvimento, FP-BHS\u2014Biomedical and Health Sciences Resarci Unit, FFP\u2014Funda\u00e7\u00e3o Fernando Pessoa, 4249-004 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9157-5541","authenticated-orcid":false,"given":"Raquel","family":"Soares","sequence":"additional","affiliation":[{"name":"Biochemistry Unit, Department of Biomedicine, Faculty of Medicine, University of Porto (FMUP), Al. Prof. Hern\u00e2ni Monteiro, 4200-319 Porto, Portugal"},{"name":"i3S\u2014Instituto de Inova\u00e7\u00e3o e Investiga\u00e7\u00e3o em Sa\u00fade, University of Porto, 4200-135 Porto, Portugal"}]}],"member":"1968","published-online":{"date-parts":[[2023,10,11]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"S120","DOI":"10.1038\/ijo.2008.247","article-title":"WHO recognition of the global obesity epidemic","volume":"32","author":"James","year":"2008","journal-title":"Int. J. Obes."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"97","DOI":"10.36713\/epra12421","article-title":"Obesity as a risk factor for different types of cancer","volume":"8","author":"Tzenios","year":"2023","journal-title":"EPRA Int. J. Multidiscip. Res. (IJMR)"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"66","DOI":"10.1038\/s41572-019-0111-2","article-title":"Breast cancer","volume":"5","author":"Harbeck","year":"2019","journal-title":"Nat. Rev. Dis. 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