Spatial protein heterogeneity analysis in frozen tissues to evaluate tumor heterogeneity.

A new workflow for protein-based tumor heterogeneity probing in tissues is here presented. Tumor heterogeneity is believed to be key for therapy failure and differences in prognosis in cancer patients. Comprehending tumor heterogeneity, especially at the protein level, is critical for tracking tumor...

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Autores principales:	Anna Fomitcheva-Khartchenko, Maria Anna Rapsomaniki, Bettina Sobottka, Peter Schraml, Govind V Kaigala
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/1e8bcb48c0d342fabf7746449977b0b2
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spelling	oai:doaj.org-article:1e8bcb48c0d342fabf7746449977b0b22021-12-02T20:12:40ZSpatial protein heterogeneity analysis in frozen tissues to evaluate tumor heterogeneity.1932-620310.1371/journal.pone.0259332https://doaj.org/article/1e8bcb48c0d342fabf7746449977b0b22021-01-01T00:00:00Zhttps://doi.org/10.1371/journal.pone.0259332https://doaj.org/toc/1932-6203A new workflow for protein-based tumor heterogeneity probing in tissues is here presented. Tumor heterogeneity is believed to be key for therapy failure and differences in prognosis in cancer patients. Comprehending tumor heterogeneity, especially at the protein level, is critical for tracking tumor evolution, and showing the presence of different phenotypical variants and their location with respect to tissue architecture. Although a variety of techniques is available for quantifying protein expression, the heterogeneity observed in the tissue is rarely addressed. The proposed method is validated in breast cancer fresh-frozen tissues derived from five patients. Protein expression is quantified on the tissue regions of interest (ROI) with a resolution of up to 100 μm in diameter. High heterogeneity values across the analyzed patients in proteins such as cytokeratin 7, β-actin and epidermal growth factor receptor (EGFR) using a Shannon entropy analysis are observed. Additionally, ROIs are clustered according to their expression levels, showing their location in the tissue section, and highlighting that similar phenotypical variants are not always located in neighboring regions. Interestingly, a patient with a phenotype related to increased aggressiveness of the tumor presents a unique protein expression pattern. In summary, a workflow for the localized extraction and protein analysis of regions of interest from frozen tissues, enabling the evaluation of tumor heterogeneity at the protein level is presented.Anna Fomitcheva-KhartchenkoMaria Anna RapsomanikiBettina SobottkaPeter SchramlGovind V KaigalaPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 16, Iss 11, p e0259332 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Anna Fomitcheva-Khartchenko Maria Anna Rapsomaniki Bettina Sobottka Peter Schraml Govind V Kaigala Spatial protein heterogeneity analysis in frozen tissues to evaluate tumor heterogeneity.
description	A new workflow for protein-based tumor heterogeneity probing in tissues is here presented. Tumor heterogeneity is believed to be key for therapy failure and differences in prognosis in cancer patients. Comprehending tumor heterogeneity, especially at the protein level, is critical for tracking tumor evolution, and showing the presence of different phenotypical variants and their location with respect to tissue architecture. Although a variety of techniques is available for quantifying protein expression, the heterogeneity observed in the tissue is rarely addressed. The proposed method is validated in breast cancer fresh-frozen tissues derived from five patients. Protein expression is quantified on the tissue regions of interest (ROI) with a resolution of up to 100 μm in diameter. High heterogeneity values across the analyzed patients in proteins such as cytokeratin 7, β-actin and epidermal growth factor receptor (EGFR) using a Shannon entropy analysis are observed. Additionally, ROIs are clustered according to their expression levels, showing their location in the tissue section, and highlighting that similar phenotypical variants are not always located in neighboring regions. Interestingly, a patient with a phenotype related to increased aggressiveness of the tumor presents a unique protein expression pattern. In summary, a workflow for the localized extraction and protein analysis of regions of interest from frozen tissues, enabling the evaluation of tumor heterogeneity at the protein level is presented.
format	article
author	Anna Fomitcheva-Khartchenko Maria Anna Rapsomaniki Bettina Sobottka Peter Schraml Govind V Kaigala
author_facet	Anna Fomitcheva-Khartchenko Maria Anna Rapsomaniki Bettina Sobottka Peter Schraml Govind V Kaigala
author_sort	Anna Fomitcheva-Khartchenko
title	Spatial protein heterogeneity analysis in frozen tissues to evaluate tumor heterogeneity.
title_short	Spatial protein heterogeneity analysis in frozen tissues to evaluate tumor heterogeneity.
title_full	Spatial protein heterogeneity analysis in frozen tissues to evaluate tumor heterogeneity.
title_fullStr	Spatial protein heterogeneity analysis in frozen tissues to evaluate tumor heterogeneity.
title_full_unstemmed	Spatial protein heterogeneity analysis in frozen tissues to evaluate tumor heterogeneity.
title_sort	spatial protein heterogeneity analysis in frozen tissues to evaluate tumor heterogeneity.
publisher	Public Library of Science (PLoS)
publishDate	2021
url	https://doaj.org/article/1e8bcb48c0d342fabf7746449977b0b2
work_keys_str_mv	AT annafomitchevakhartchenko spatialproteinheterogeneityanalysisinfrozentissuestoevaluatetumorheterogeneity AT mariaannarapsomaniki spatialproteinheterogeneityanalysisinfrozentissuestoevaluatetumorheterogeneity AT bettinasobottka spatialproteinheterogeneityanalysisinfrozentissuestoevaluatetumorheterogeneity AT peterschraml spatialproteinheterogeneityanalysisinfrozentissuestoevaluatetumorheterogeneity AT govindvkaigala spatialproteinheterogeneityanalysisinfrozentissuestoevaluatetumorheterogeneity
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Spatial protein heterogeneity analysis in frozen tissues to evaluate tumor heterogeneity.

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