The Clinicopathological Significance of BiP/GRP-78 in Breast Cancer: A Meta-Analysis of Public Datasets and Immunohistochemical Detection
The endoplasmic reticulum chaperone BiP (also known as GRP-78 or HSPA5) maintains protein folding to allow cell proliferation and survival and has been implicated in carcinogenesis, tumor progression, and therapy resistance. BiP’s association with clinical factors and prognostic potential in breast...
| Main Authors: | , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2022-11-01
|
| Series: | Current Oncology |
| Subjects: | |
| Online Access: | https://www.mdpi.com/1718-7729/29/12/710 |
| _version_ | 1797460770730016768 |
|---|---|
| author | Inês Direito Daniela Gomes Fátima Liliana Monteiro Isa Carneiro João Lobo Rui Henrique Carmen Jerónimo Luisa Alejandra Helguero |
| author_facet | Inês Direito Daniela Gomes Fátima Liliana Monteiro Isa Carneiro João Lobo Rui Henrique Carmen Jerónimo Luisa Alejandra Helguero |
| author_sort | Inês Direito |
| collection | DOAJ |
| description | The endoplasmic reticulum chaperone BiP (also known as GRP-78 or HSPA5) maintains protein folding to allow cell proliferation and survival and has been implicated in carcinogenesis, tumor progression, and therapy resistance. BiP’s 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’s 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. |
| first_indexed | 2024-03-09T17:09:47Z |
| format | Article |
| id | doaj.art-db130825249a4125b5ceeba757a41084 |
| institution | Directory Open Access Journal |
| issn | 1198-0052 1718-7729 |
| language | English |
| last_indexed | 2024-03-09T17:09:47Z |
| publishDate | 2022-11-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Current Oncology |
| spelling | doaj.art-db130825249a4125b5ceeba757a410842023-11-24T14:12:12ZengMDPI AGCurrent Oncology1198-00521718-77292022-11-0129129066908710.3390/curroncol29120710The Clinicopathological Significance of BiP/GRP-78 in Breast Cancer: A Meta-Analysis of Public Datasets and Immunohistochemical DetectionInês Direito0Daniela Gomes1Fátima Liliana Monteiro2Isa Carneiro3João Lobo4Rui Henrique5Carmen Jerónimo6Luisa Alejandra Helguero7iBiMED—Institute of Biomedicine, University of Aveiro, Agra do Crasto 30, 3810-193 Aveiro, PortugaliBiMED—Institute of Biomedicine, University of Aveiro, Agra do Crasto 30, 3810-193 Aveiro, PortugaliBiMED—Institute of Biomedicine, University of Aveiro, Agra do Crasto 30, 3810-193 Aveiro, PortugalDepartment of Pathology, Portuguese Oncology Institute of Porto (IPO Porto), R. Dr. António Bernardino de Almeida, 4200-072 Porto, PortugalDepartment of Pathology, Portuguese Oncology Institute of Porto (IPO Porto), R. Dr. António Bernardino de Almeida, 4200-072 Porto, PortugalDepartment of Pathology, Portuguese Oncology Institute of Porto (IPO Porto), R. Dr. António Bernardino de Almeida, 4200-072 Porto, PortugalDepartment of Pathology, Portuguese Oncology Institute of Porto (IPO Porto), R. Dr. António Bernardino de Almeida, 4200-072 Porto, PortugaliBiMED—Institute of Biomedicine, University of Aveiro, Agra do Crasto 30, 3810-193 Aveiro, PortugalThe endoplasmic reticulum chaperone BiP (also known as GRP-78 or HSPA5) maintains protein folding to allow cell proliferation and survival and has been implicated in carcinogenesis, tumor progression, and therapy resistance. BiP’s 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’s 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.https://www.mdpi.com/1718-7729/29/12/710unfolded protein responsebreast cancer outcomestherapy resistanceTCGAimmunohistochemistryBiP/GRP-78 |
| spellingShingle | Inês Direito Daniela Gomes Fátima Liliana Monteiro Isa Carneiro João Lobo Rui Henrique Carmen Jerónimo Luisa Alejandra Helguero The Clinicopathological Significance of BiP/GRP-78 in Breast Cancer: A Meta-Analysis of Public Datasets and Immunohistochemical Detection Current Oncology unfolded protein response breast cancer outcomes therapy resistance TCGA immunohistochemistry BiP/GRP-78 |
| title | The Clinicopathological Significance of BiP/GRP-78 in Breast Cancer: A Meta-Analysis of Public Datasets and Immunohistochemical Detection |
| title_full | The Clinicopathological Significance of BiP/GRP-78 in Breast Cancer: A Meta-Analysis of Public Datasets and Immunohistochemical Detection |
| title_fullStr | The Clinicopathological Significance of BiP/GRP-78 in Breast Cancer: A Meta-Analysis of Public Datasets and Immunohistochemical Detection |
| title_full_unstemmed | The Clinicopathological Significance of BiP/GRP-78 in Breast Cancer: A Meta-Analysis of Public Datasets and Immunohistochemical Detection |
| title_short | The Clinicopathological Significance of BiP/GRP-78 in Breast Cancer: A Meta-Analysis of Public Datasets and Immunohistochemical Detection |
| title_sort | clinicopathological significance of bip grp 78 in breast cancer a meta analysis of public datasets and immunohistochemical detection |
| topic | unfolded protein response breast cancer outcomes therapy resistance TCGA immunohistochemistry BiP/GRP-78 |
| url | https://www.mdpi.com/1718-7729/29/12/710 |
| work_keys_str_mv | AT inesdireito theclinicopathologicalsignificanceofbipgrp78inbreastcancerametaanalysisofpublicdatasetsandimmunohistochemicaldetection AT danielagomes theclinicopathologicalsignificanceofbipgrp78inbreastcancerametaanalysisofpublicdatasetsandimmunohistochemicaldetection AT fatimalilianamonteiro theclinicopathologicalsignificanceofbipgrp78inbreastcancerametaanalysisofpublicdatasetsandimmunohistochemicaldetection AT isacarneiro theclinicopathologicalsignificanceofbipgrp78inbreastcancerametaanalysisofpublicdatasetsandimmunohistochemicaldetection AT joaolobo theclinicopathologicalsignificanceofbipgrp78inbreastcancerametaanalysisofpublicdatasetsandimmunohistochemicaldetection AT ruihenrique theclinicopathologicalsignificanceofbipgrp78inbreastcancerametaanalysisofpublicdatasetsandimmunohistochemicaldetection AT carmenjeronimo theclinicopathologicalsignificanceofbipgrp78inbreastcancerametaanalysisofpublicdatasetsandimmunohistochemicaldetection AT luisaalejandrahelguero theclinicopathologicalsignificanceofbipgrp78inbreastcancerametaanalysisofpublicdatasetsandimmunohistochemicaldetection AT inesdireito clinicopathologicalsignificanceofbipgrp78inbreastcancerametaanalysisofpublicdatasetsandimmunohistochemicaldetection AT danielagomes clinicopathologicalsignificanceofbipgrp78inbreastcancerametaanalysisofpublicdatasetsandimmunohistochemicaldetection AT fatimalilianamonteiro clinicopathologicalsignificanceofbipgrp78inbreastcancerametaanalysisofpublicdatasetsandimmunohistochemicaldetection AT isacarneiro clinicopathologicalsignificanceofbipgrp78inbreastcancerametaanalysisofpublicdatasetsandimmunohistochemicaldetection AT joaolobo clinicopathologicalsignificanceofbipgrp78inbreastcancerametaanalysisofpublicdatasetsandimmunohistochemicaldetection AT ruihenrique clinicopathologicalsignificanceofbipgrp78inbreastcancerametaanalysisofpublicdatasetsandimmunohistochemicaldetection AT carmenjeronimo clinicopathologicalsignificanceofbipgrp78inbreastcancerametaanalysisofpublicdatasetsandimmunohistochemicaldetection AT luisaalejandrahelguero clinicopathologicalsignificanceofbipgrp78inbreastcancerametaanalysisofpublicdatasetsandimmunohistochemicaldetection |