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Proteomic and functional characterization of intra-tumor heterogeneity in human endometrial cancer

Endometrial cancer is one of the most frequently diagnosed gynecological cancers worldwide, and its prevalence has increased by more than 50% over the last two decades. Despite the understanding of the major signaling pathways driving the growth and metastasis of endometrial cancer, clinical trials...

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Autores principales: Jamaluddin, M. Fairuz B., Ko, Yi-An, Ghosh, Arnab, Syed, Shafiq M., Ius, Yvette, O’Sullivan, Rachel, Netherton, Jacob K., Baker, Mark A., Nahar, Pravin, Jaaback, Kenneth, Tanwar, Pradeep S.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9512672/
https://www.ncbi.nlm.nih.gov/pubmed/36103879
http://dx.doi.org/10.1016/j.xcrm.2022.100738
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author Jamaluddin, M. Fairuz B.
Ko, Yi-An
Ghosh, Arnab
Syed, Shafiq M.
Ius, Yvette
O’Sullivan, Rachel
Netherton, Jacob K.
Baker, Mark A.
Nahar, Pravin
Jaaback, Kenneth
Tanwar, Pradeep S.
author_facet Jamaluddin, M. Fairuz B.
Ko, Yi-An
Ghosh, Arnab
Syed, Shafiq M.
Ius, Yvette
O’Sullivan, Rachel
Netherton, Jacob K.
Baker, Mark A.
Nahar, Pravin
Jaaback, Kenneth
Tanwar, Pradeep S.
author_sort Jamaluddin, M. Fairuz B.
collection PubMed
description Endometrial cancer is one of the most frequently diagnosed gynecological cancers worldwide, and its prevalence has increased by more than 50% over the last two decades. Despite the understanding of the major signaling pathways driving the growth and metastasis of endometrial cancer, clinical trials targeting these signals have reported poor outcomes. The heterogeneous nature of endometrial cancer is suspected to be one of the key reasons for the failure of targeted therapies. In this study, we perform a sequential window acquisition of all theoretical fragment ion spectra (SWATH)-based comparative proteomic analysis of 63 tumor biopsies collected from 20 patients and define differences in protein signature in multiple regions of the same tumor. We develop organoids from multiple biopsies collected from the same tumor and show that organoids capture heterogeneity in endometrial cancer growth. Overall, using quantitative proteomics and patient-derived organoids, we define the heterogeneous nature of endometrial cancer within a patient’s tumor.
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spelling pubmed-95126722022-09-28 Proteomic and functional characterization of intra-tumor heterogeneity in human endometrial cancer Jamaluddin, M. Fairuz B. Ko, Yi-An Ghosh, Arnab Syed, Shafiq M. Ius, Yvette O’Sullivan, Rachel Netherton, Jacob K. Baker, Mark A. Nahar, Pravin Jaaback, Kenneth Tanwar, Pradeep S. Cell Rep Med Article Endometrial cancer is one of the most frequently diagnosed gynecological cancers worldwide, and its prevalence has increased by more than 50% over the last two decades. Despite the understanding of the major signaling pathways driving the growth and metastasis of endometrial cancer, clinical trials targeting these signals have reported poor outcomes. The heterogeneous nature of endometrial cancer is suspected to be one of the key reasons for the failure of targeted therapies. In this study, we perform a sequential window acquisition of all theoretical fragment ion spectra (SWATH)-based comparative proteomic analysis of 63 tumor biopsies collected from 20 patients and define differences in protein signature in multiple regions of the same tumor. We develop organoids from multiple biopsies collected from the same tumor and show that organoids capture heterogeneity in endometrial cancer growth. Overall, using quantitative proteomics and patient-derived organoids, we define the heterogeneous nature of endometrial cancer within a patient’s tumor. Elsevier 2022-09-13 /pmc/articles/PMC9512672/ /pubmed/36103879 http://dx.doi.org/10.1016/j.xcrm.2022.100738 Text en © 2022 The Author(s) https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
spellingShingle Article
Jamaluddin, M. Fairuz B.
Ko, Yi-An
Ghosh, Arnab
Syed, Shafiq M.
Ius, Yvette
O’Sullivan, Rachel
Netherton, Jacob K.
Baker, Mark A.
Nahar, Pravin
Jaaback, Kenneth
Tanwar, Pradeep S.
Proteomic and functional characterization of intra-tumor heterogeneity in human endometrial cancer
title Proteomic and functional characterization of intra-tumor heterogeneity in human endometrial cancer
title_full Proteomic and functional characterization of intra-tumor heterogeneity in human endometrial cancer
title_fullStr Proteomic and functional characterization of intra-tumor heterogeneity in human endometrial cancer
title_full_unstemmed Proteomic and functional characterization of intra-tumor heterogeneity in human endometrial cancer
title_short Proteomic and functional characterization of intra-tumor heterogeneity in human endometrial cancer
title_sort proteomic and functional characterization of intra-tumor heterogeneity in human endometrial cancer
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9512672/
https://www.ncbi.nlm.nih.gov/pubmed/36103879
http://dx.doi.org/10.1016/j.xcrm.2022.100738
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