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TROP2 as Patient-Tailoring but Not Prognostic Biomarker for Breast Cancer

PURPOSE: Trophoblast cell surface antigen 2 (TROP2) has emerged as a promising target of antibody-drug conjugates (ADCs) for triple-negative breast cancer (TNBC), as well as other breast cancers (BCs). This study aims to investigate the biomarker value of TROP2 for patient-tailoring and prognostic f...

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Autores principales: Liu, Xiaoyue, Zhou, Tianhao, Wang, Yongmei, Pei, Min, Wang, Guifeng, Chu, Wendi, Wang, Qi, Du, Shaoqian, Wang, Hongxia, Wang, Chunhe
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Dove 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9078428/
https://www.ncbi.nlm.nih.gov/pubmed/35535168
http://dx.doi.org/10.2147/OTT.S354048
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author Liu, Xiaoyue
Zhou, Tianhao
Wang, Yongmei
Pei, Min
Wang, Guifeng
Chu, Wendi
Wang, Qi
Du, Shaoqian
Wang, Hongxia
Wang, Chunhe
author_facet Liu, Xiaoyue
Zhou, Tianhao
Wang, Yongmei
Pei, Min
Wang, Guifeng
Chu, Wendi
Wang, Qi
Du, Shaoqian
Wang, Hongxia
Wang, Chunhe
author_sort Liu, Xiaoyue
collection PubMed
description PURPOSE: Trophoblast cell surface antigen 2 (TROP2) has emerged as a promising target of antibody-drug conjugates (ADCs) for triple-negative breast cancer (TNBC), as well as other breast cancers (BCs). This study aims to investigate the biomarker value of TROP2 for patient-tailoring and prognostic for BC patients, including TNBC. METHODS: The levels of TROP2 expression in 404 Chinese BC tissues on tissue microarrays (TMAs) were quantified by immunohistochemistry and their correlations to the clinicopathological factors and the overall survival rate were analyzed. Also, BC cell lines and patient-derived organoids (PDOs) with different TROP2 expression levels were employed to investigate the correlation between TROP2 expression levels and the therapeutic responses to DS001, a TROP2-directed ADC molecule with stable linker and potent payload. RESULTS: TROP2 overexpression was identified in significantly more (P = 0.046) tumor tissues (41.08%, 99/241) than normal adjacent tissues (31.29%, 51/163) from Chinese BC patients, and in significantly more (P = 0.024) TNBC patients (59.38%, 19/32) than in other BC types (38.28%, 80/209). BC cell line with the lowest TROP2 expression level failed to respond to DS001 treatment. The levels of TROP2 expression were determined to be significantly correlated with the potencies of DS001 treatment, but not with the overall survival rates of the patients. CONCLUSION: Our results demonstrated that TROP2 could serve as a patient-tailoring and predictive biomarker for ADC therapeutics but not as a general prognostic biomarker to predicate patient survival.
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spelling pubmed-90784282022-05-08 TROP2 as Patient-Tailoring but Not Prognostic Biomarker for Breast Cancer Liu, Xiaoyue Zhou, Tianhao Wang, Yongmei Pei, Min Wang, Guifeng Chu, Wendi Wang, Qi Du, Shaoqian Wang, Hongxia Wang, Chunhe Onco Targets Ther Original Research PURPOSE: Trophoblast cell surface antigen 2 (TROP2) has emerged as a promising target of antibody-drug conjugates (ADCs) for triple-negative breast cancer (TNBC), as well as other breast cancers (BCs). This study aims to investigate the biomarker value of TROP2 for patient-tailoring and prognostic for BC patients, including TNBC. METHODS: The levels of TROP2 expression in 404 Chinese BC tissues on tissue microarrays (TMAs) were quantified by immunohistochemistry and their correlations to the clinicopathological factors and the overall survival rate were analyzed. Also, BC cell lines and patient-derived organoids (PDOs) with different TROP2 expression levels were employed to investigate the correlation between TROP2 expression levels and the therapeutic responses to DS001, a TROP2-directed ADC molecule with stable linker and potent payload. RESULTS: TROP2 overexpression was identified in significantly more (P = 0.046) tumor tissues (41.08%, 99/241) than normal adjacent tissues (31.29%, 51/163) from Chinese BC patients, and in significantly more (P = 0.024) TNBC patients (59.38%, 19/32) than in other BC types (38.28%, 80/209). BC cell line with the lowest TROP2 expression level failed to respond to DS001 treatment. The levels of TROP2 expression were determined to be significantly correlated with the potencies of DS001 treatment, but not with the overall survival rates of the patients. CONCLUSION: Our results demonstrated that TROP2 could serve as a patient-tailoring and predictive biomarker for ADC therapeutics but not as a general prognostic biomarker to predicate patient survival. Dove 2022-05-03 /pmc/articles/PMC9078428/ /pubmed/35535168 http://dx.doi.org/10.2147/OTT.S354048 Text en © 2022 Liu et al. https://creativecommons.org/licenses/by-nc/3.0/This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License (http://creativecommons.org/licenses/by-nc/3.0/ (https://creativecommons.org/licenses/by-nc/3.0/) ). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms (https://www.dovepress.com/terms.php).
spellingShingle Original Research
Liu, Xiaoyue
Zhou, Tianhao
Wang, Yongmei
Pei, Min
Wang, Guifeng
Chu, Wendi
Wang, Qi
Du, Shaoqian
Wang, Hongxia
Wang, Chunhe
TROP2 as Patient-Tailoring but Not Prognostic Biomarker for Breast Cancer
title TROP2 as Patient-Tailoring but Not Prognostic Biomarker for Breast Cancer
title_full TROP2 as Patient-Tailoring but Not Prognostic Biomarker for Breast Cancer
title_fullStr TROP2 as Patient-Tailoring but Not Prognostic Biomarker for Breast Cancer
title_full_unstemmed TROP2 as Patient-Tailoring but Not Prognostic Biomarker for Breast Cancer
title_short TROP2 as Patient-Tailoring but Not Prognostic Biomarker for Breast Cancer
title_sort trop2 as patient-tailoring but not prognostic biomarker for breast cancer
topic Original Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9078428/
https://www.ncbi.nlm.nih.gov/pubmed/35535168
http://dx.doi.org/10.2147/OTT.S354048
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