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BiP\u2019s association with clinical factors and prognostic potential in breast cancer remains unclear. In this work, three types of analysis were conducted to improve the knowledge of BiP\u2019s clinicopathological potential: (1) analysis of publicly available RNA-seq and proteomics datasets stratified as high and low quartiles; (2) a systematic review and meta-analysis of immunohistochemical detection of BIP; (3) confirmation of findings by BiP immunohistochemical detection in two luminal-like breast cancer small cohorts of paired samples (pre- vs. post-endocrine therapy, and primary pre- vs. metastasis post-endocrine therapy). The TCGA PanCancer dataset and CPTAC showed groups with high BiP mRNA and protein associated with HER2, basal-like subtypes, and higher immune scores. The meta-analysis of BiP immunohistochemistry disclosed an association between higher BiP positivity and reduced relapse-free survival. BiP immunohistochemistry confirmed increased BiP expression in metastasis, an association of BiP positivity with HER2 expression, and nuclear BiP localization with higher a tumor stage and poor outcome. Therefore, three independent approaches showed that BiP protein is associated with worse outcomes and holds prognostic potential for breast cancer.<\/jats:p>","DOI":"10.3390\/curroncol29120710","type":"journal-article","created":{"date-parts":[[2022,11,23]],"date-time":"2022-11-23T03:48:12Z","timestamp":1669175292000},"page":"9066-9087","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["The Clinicopathological Significance of BiP\/GRP-78 in Breast Cancer: A Meta-Analysis of Public Datasets and Immunohistochemical Detection"],"prefix":"10.3390","volume":"29","author":[{"given":"In\u00eas","family":"Direito","sequence":"first","affiliation":[{"name":"iBiMED\u2014Institute of Biomedicine, University of Aveiro, Agra do Crasto 30, 3810-193 Aveiro, Portugal"}]},{"given":"Daniela","family":"Gomes","sequence":"additional","affiliation":[{"name":"iBiMED\u2014Institute of Biomedicine, University of Aveiro, Agra do Crasto 30, 3810-193 Aveiro, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8438-0332","authenticated-orcid":false,"given":"F\u00e1tima Liliana","family":"Monteiro","sequence":"additional","affiliation":[{"name":"iBiMED\u2014Institute of Biomedicine, University of Aveiro, Agra do Crasto 30, 3810-193 Aveiro, Portugal"}]},{"given":"Isa","family":"Carneiro","sequence":"additional","affiliation":[{"name":"Department of Pathology, Portuguese Oncology Institute of Porto (IPO Porto), R. Dr. Ant\u00f3nio Bernardino de Almeida, 4200-072 Porto, Portugal"},{"name":"Cancer Biology and Epigenetics Group, IPO Porto Research Center (CI-IPOP), Portuguese Oncology Institute of Porto (IPO Porto)\/Porto Comprehensive Cancer Centre (Porto.CCC) & RISE@CI-IPOP (Health Research Network), R. Dr. Ant\u00f3nio Bernardino de Almeida, 4200-072 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6829-1391","authenticated-orcid":false,"given":"Jo\u00e3o","family":"Lobo","sequence":"additional","affiliation":[{"name":"Department of Pathology, Portuguese Oncology Institute of Porto (IPO Porto), R. Dr. Ant\u00f3nio Bernardino de Almeida, 4200-072 Porto, Portugal"},{"name":"Cancer Biology and Epigenetics Group, IPO Porto Research Center (CI-IPOP), Portuguese Oncology Institute of Porto (IPO Porto)\/Porto Comprehensive Cancer Centre (Porto.CCC) & RISE@CI-IPOP (Health Research Network), R. Dr. Ant\u00f3nio Bernardino de Almeida, 4200-072 Porto, Portugal"},{"name":"Department of Pathology and Molecular Immunology, School of Medicine & Biomedical Sciences, University of Porto (ICBAS-UP), Rua Jorge Viterbo Ferreira 228, 4050-513 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3171-4666","authenticated-orcid":false,"given":"Rui","family":"Henrique","sequence":"additional","affiliation":[{"name":"Department of Pathology, Portuguese Oncology Institute of Porto (IPO Porto), R. Dr. Ant\u00f3nio Bernardino de Almeida, 4200-072 Porto, Portugal"},{"name":"Cancer Biology and Epigenetics Group, IPO Porto Research Center (CI-IPOP), Portuguese Oncology Institute of Porto (IPO Porto)\/Porto Comprehensive Cancer Centre (Porto.CCC) & RISE@CI-IPOP (Health Research Network), R. Dr. Ant\u00f3nio Bernardino de Almeida, 4200-072 Porto, Portugal"},{"name":"Department of Pathology and Molecular Immunology, School of Medicine & Biomedical Sciences, University of Porto (ICBAS-UP), Rua Jorge Viterbo Ferreira 228, 4050-513 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4186-5345","authenticated-orcid":false,"given":"Carmen","family":"Jer\u00f3nimo","sequence":"additional","affiliation":[{"name":"Department of Pathology, Portuguese Oncology Institute of Porto (IPO Porto), R. Dr. Ant\u00f3nio Bernardino de Almeida, 4200-072 Porto, Portugal"},{"name":"Cancer Biology and Epigenetics Group, IPO Porto Research Center (CI-IPOP), Portuguese Oncology Institute of Porto (IPO Porto)\/Porto Comprehensive Cancer Centre (Porto.CCC) & RISE@CI-IPOP (Health Research Network), R. Dr. Ant\u00f3nio Bernardino de Almeida, 4200-072 Porto, Portugal"},{"name":"Department of Pathology and Molecular Immunology, School of Medicine & Biomedical Sciences, University of Porto (ICBAS-UP), Rua Jorge Viterbo Ferreira 228, 4050-513 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8237-2390","authenticated-orcid":false,"given":"Luisa Alejandra","family":"Helguero","sequence":"additional","affiliation":[{"name":"iBiMED\u2014Institute of Biomedicine, University of Aveiro, Agra do Crasto 30, 3810-193 Aveiro, Portugal"}]}],"member":"1968","published-online":{"date-parts":[[2022,11,23]]},"reference":[{"key":"ref_1","unstructured":"(2021, December 27). Cancer Fact Sheets: Breast Cancer. 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