Nectin-4 Expression Is an Independent Prognostic Biomarker and Associated With Better Survival in Triple-Negative Breast Cancer
Background: Triple-negative breast cancer (TNBC) represents about 10-20% of all invasive breast cancers and is associated with a poor prognosis. The nectin cell adhesion protein 4 (Nectin-4) is a junction protein involved in the formation and maintenance of cell junctions. Nectin-4 has previously sh...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2019-09-01
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| Series: | Frontiers in Medicine |
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| Online Access: | https://www.frontiersin.org/article/10.3389/fmed.2019.00200/full |
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| author | Jasmin Zeindler Savas Deniz Soysal Savas Deniz Soysal Salvatore Piscuoglio Salvatore Piscuoglio Charlotte K. Y. Ng Robert Mechera Robert Mechera Andrej Isaak Walter Paul Weber Simone Muenst Simone Muenst Christian Kurzeder Christian Kurzeder |
| author_facet | Jasmin Zeindler Savas Deniz Soysal Savas Deniz Soysal Salvatore Piscuoglio Salvatore Piscuoglio Charlotte K. Y. Ng Robert Mechera Robert Mechera Andrej Isaak Walter Paul Weber Simone Muenst Simone Muenst Christian Kurzeder Christian Kurzeder |
| author_sort | Jasmin Zeindler |
| collection | DOAJ |
| description | Background: Triple-negative breast cancer (TNBC) represents about 10-20% of all invasive breast cancers and is associated with a poor prognosis. The nectin cell adhesion protein 4 (Nectin-4) is a junction protein involved in the formation and maintenance of cell junctions. Nectin-4 has previously shown to be expressed in about 60% of TNBC as well as in TNBC metastases, but to be absent in normal breast tissue, which makes it a potential specific target for TNBC therapy. Previous studies have shown an association of Nectin-4 protein expression with worse prognosis in TNBC in a small patient cohort. The aim of our study was to explore the role of Nectin-4 in TNBC and confirm its impact on survival in a larger TNBC patient cohort.Material and Methods: We performed immunohistochemical staining for Nectin-4 on a tissue microarray encompassing 148 TNBC cases with detailed clinical annotation and outcomes data.Results: A high expression of Nectin-4 was present in 86 (58%) of the 148 TNBC cases. In multivariate survival analysis, high expression of Nectin-4 was associated with a significantly better overall survival when compared with low expression of Nectin-4 (p < 0.001). Nectin-4-high expression was also significantly associated with a lower tumor stage (p = 0.025) and pN0 lymph node stage (p = 0.034).Conclusion: Our results confirm that expression of Nectin-4 serves as a potential prognostic marker in TNBC and is associated with a significantly better overall survival. In addition, Nectin-4 represents a potential target in TNBC, and its role in molecular defined breast cancer subtype should be investigated in larger patient cohorts. |
| first_indexed | 2024-12-12T17:54:08Z |
| format | Article |
| id | doaj.art-9cfc36042f51461e86cef6011da98873 |
| institution | Directory Open Access Journal |
| issn | 2296-858X |
| language | English |
| last_indexed | 2024-12-12T17:54:08Z |
| publishDate | 2019-09-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Medicine |
| spelling | doaj.art-9cfc36042f51461e86cef6011da988732022-12-22T00:16:44ZengFrontiers Media S.A.Frontiers in Medicine2296-858X2019-09-01610.3389/fmed.2019.00200486450Nectin-4 Expression Is an Independent Prognostic Biomarker and Associated With Better Survival in Triple-Negative Breast CancerJasmin Zeindler0Savas Deniz Soysal1Savas Deniz Soysal2Salvatore Piscuoglio3Salvatore Piscuoglio4Charlotte K. Y. Ng5Robert Mechera6Robert Mechera7Andrej Isaak8Walter Paul Weber9Simone Muenst10Simone Muenst11Christian Kurzeder12Christian Kurzeder13Breast Center, University Hospital Basel and University of Basel, Basel, SwitzerlandVisceral Surgery Research Laboratory, Clarunis, Department of Biomedicine, University of Basel, Basel, SwitzerlandDepartment of Surgery, Clarunis University Center for Gastrointestinal and Liver Diseases Basel, Basel, SwitzerlandVisceral Surgery Research Laboratory, Clarunis, Department of Biomedicine, University of Basel, Basel, SwitzerlandInstitute of Medical Genetics and Pathology, University Hospital Basel, Basel, SwitzerlandInstitute of Medical Genetics and Pathology, University Hospital Basel, Basel, SwitzerlandVisceral Surgery Research Laboratory, Clarunis, Department of Biomedicine, University of Basel, Basel, SwitzerlandDepartment of Surgery, Clarunis University Center for Gastrointestinal and Liver Diseases Basel, Basel, SwitzerlandDepartment of Vascular and Endovascular Surgery, University Hospital Basel, Basel, SwitzerlandBreast Center, University Hospital Basel and University of Basel, Basel, SwitzerlandBreast Center, University Hospital Basel and University of Basel, Basel, SwitzerlandInstitute of Medical Genetics and Pathology, University Hospital Basel, Basel, SwitzerlandBreast Center, University Hospital Basel and University of Basel, Basel, SwitzerlandDepartment of Obstetrics and Gynecology, University Hospital of Basel, Basel, SwitzerlandBackground: Triple-negative breast cancer (TNBC) represents about 10-20% of all invasive breast cancers and is associated with a poor prognosis. The nectin cell adhesion protein 4 (Nectin-4) is a junction protein involved in the formation and maintenance of cell junctions. Nectin-4 has previously shown to be expressed in about 60% of TNBC as well as in TNBC metastases, but to be absent in normal breast tissue, which makes it a potential specific target for TNBC therapy. Previous studies have shown an association of Nectin-4 protein expression with worse prognosis in TNBC in a small patient cohort. The aim of our study was to explore the role of Nectin-4 in TNBC and confirm its impact on survival in a larger TNBC patient cohort.Material and Methods: We performed immunohistochemical staining for Nectin-4 on a tissue microarray encompassing 148 TNBC cases with detailed clinical annotation and outcomes data.Results: A high expression of Nectin-4 was present in 86 (58%) of the 148 TNBC cases. In multivariate survival analysis, high expression of Nectin-4 was associated with a significantly better overall survival when compared with low expression of Nectin-4 (p < 0.001). Nectin-4-high expression was also significantly associated with a lower tumor stage (p = 0.025) and pN0 lymph node stage (p = 0.034).Conclusion: Our results confirm that expression of Nectin-4 serves as a potential prognostic marker in TNBC and is associated with a significantly better overall survival. In addition, Nectin-4 represents a potential target in TNBC, and its role in molecular defined breast cancer subtype should be investigated in larger patient cohorts.https://www.frontiersin.org/article/10.3389/fmed.2019.00200/fullNectin-4breast cancerbiomarkersprognosistriple-negative breast cancer |
| spellingShingle | Jasmin Zeindler Savas Deniz Soysal Savas Deniz Soysal Salvatore Piscuoglio Salvatore Piscuoglio Charlotte K. Y. Ng Robert Mechera Robert Mechera Andrej Isaak Walter Paul Weber Simone Muenst Simone Muenst Christian Kurzeder Christian Kurzeder Nectin-4 Expression Is an Independent Prognostic Biomarker and Associated With Better Survival in Triple-Negative Breast Cancer Frontiers in Medicine Nectin-4 breast cancer biomarkers prognosis triple-negative breast cancer |
| title | Nectin-4 Expression Is an Independent Prognostic Biomarker and Associated With Better Survival in Triple-Negative Breast Cancer |
| title_full | Nectin-4 Expression Is an Independent Prognostic Biomarker and Associated With Better Survival in Triple-Negative Breast Cancer |
| title_fullStr | Nectin-4 Expression Is an Independent Prognostic Biomarker and Associated With Better Survival in Triple-Negative Breast Cancer |
| title_full_unstemmed | Nectin-4 Expression Is an Independent Prognostic Biomarker and Associated With Better Survival in Triple-Negative Breast Cancer |
| title_short | Nectin-4 Expression Is an Independent Prognostic Biomarker and Associated With Better Survival in Triple-Negative Breast Cancer |
| title_sort | nectin 4 expression is an independent prognostic biomarker and associated with better survival in triple negative breast cancer |
| topic | Nectin-4 breast cancer biomarkers prognosis triple-negative breast cancer |
| url | https://www.frontiersin.org/article/10.3389/fmed.2019.00200/full |
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