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Integrating digital pathology with transcriptomic and epigenomic tools for predicting metastatic uterine tumor aggressiveness
The incidence of new cancer cases is expected to increase significantly in the future, posing a worldwide problem. In this regard, precision oncology and its diagnostic tools are essential for developing personalized cancer treatments. Digital pathology (DP) is a particularly key strategy to study t...
Autores principales: | , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9716026/ https://www.ncbi.nlm.nih.gov/pubmed/36467415 http://dx.doi.org/10.3389/fcell.2022.1052098 |
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author | Sonzini, Giorgia Granados-Aparici, Sofia Sanegre, Sabina Diaz-Lagares, Angel Diaz-Martin, Juan de Andrea, Carlos Eritja, Núria Bao-Caamano, Aida Costa-Fraga, Nicolás García-Ros, David Salguero-Aranda, Carmen Davidson, Ben López-López, Rafael Melero, Ignacio Navarro, Samuel Ramon y Cajal, Santiago de Alava, Enrique Matias-Guiu, Xavier Noguera, Rosa |
author_facet | Sonzini, Giorgia Granados-Aparici, Sofia Sanegre, Sabina Diaz-Lagares, Angel Diaz-Martin, Juan de Andrea, Carlos Eritja, Núria Bao-Caamano, Aida Costa-Fraga, Nicolás García-Ros, David Salguero-Aranda, Carmen Davidson, Ben López-López, Rafael Melero, Ignacio Navarro, Samuel Ramon y Cajal, Santiago de Alava, Enrique Matias-Guiu, Xavier Noguera, Rosa |
author_sort | Sonzini, Giorgia |
collection | PubMed |
description | The incidence of new cancer cases is expected to increase significantly in the future, posing a worldwide problem. In this regard, precision oncology and its diagnostic tools are essential for developing personalized cancer treatments. Digital pathology (DP) is a particularly key strategy to study the interactions of tumor cells and the tumor microenvironment (TME), which play a crucial role in tumor initiation, progression and metastasis. The purpose of this study was to integrate data on the digital patterns of reticulin fiber scaffolding and the immune cell infiltrate, transcriptomic and epigenetic profiles in aggressive uterine adenocarcinoma (uADC), uterine leiomyosarcoma (uLMS) and their respective lung metastases, with the aim of obtaining key TME biomarkers that can help improve metastatic prediction and shed light on potential therapeutic targets. Automatized algorithms were used to analyze reticulin fiber architecture and immune infiltration in colocalized regions of interest (ROIs) of 133 invasive tumor front (ITF), 89 tumor niches and 70 target tissues in a total of six paired samples of uADC and nine of uLMS. Microdissected tissue from the ITF was employed for transcriptomic and epigenetic studies in primary and metastatic tumors. Reticulin fiber scaffolding was characterized by a large and loose reticular fiber network in uADC, while dense bundles were found in uLMS. Notably, more similarities between reticulin fibers were observed in paired uLMS then paired uADCs. Transcriptomic and multiplex immunofluorescence-based immune profiling showed a higher abundance of T and B cells in primary tumor and in metastatic uADC than uLMS. Moreover, the epigenetic signature of paired samples in uADCs showed more differences than paired samples in uLMS. Some epigenetic variation was also found between the ITF of metastatic uADC and uLMS. Altogether, our data suggest a correlation between morphological and molecular changes at the ITF and the degree of aggressiveness. The use of DP tools for characterizing reticulin scaffolding and immune cell infiltration at the ITF in paired samples together with information provided by omics analyses in a large cohort will hopefully help validate novel biomarkers of tumor aggressiveness, develop new drugs and improve patient quality of life in a much more efficient way. |
format | Online Article Text |
id | pubmed-9716026 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-97160262022-12-03 Integrating digital pathology with transcriptomic and epigenomic tools for predicting metastatic uterine tumor aggressiveness Sonzini, Giorgia Granados-Aparici, Sofia Sanegre, Sabina Diaz-Lagares, Angel Diaz-Martin, Juan de Andrea, Carlos Eritja, Núria Bao-Caamano, Aida Costa-Fraga, Nicolás García-Ros, David Salguero-Aranda, Carmen Davidson, Ben López-López, Rafael Melero, Ignacio Navarro, Samuel Ramon y Cajal, Santiago de Alava, Enrique Matias-Guiu, Xavier Noguera, Rosa Front Cell Dev Biol Cell and Developmental Biology The incidence of new cancer cases is expected to increase significantly in the future, posing a worldwide problem. In this regard, precision oncology and its diagnostic tools are essential for developing personalized cancer treatments. Digital pathology (DP) is a particularly key strategy to study the interactions of tumor cells and the tumor microenvironment (TME), which play a crucial role in tumor initiation, progression and metastasis. The purpose of this study was to integrate data on the digital patterns of reticulin fiber scaffolding and the immune cell infiltrate, transcriptomic and epigenetic profiles in aggressive uterine adenocarcinoma (uADC), uterine leiomyosarcoma (uLMS) and their respective lung metastases, with the aim of obtaining key TME biomarkers that can help improve metastatic prediction and shed light on potential therapeutic targets. Automatized algorithms were used to analyze reticulin fiber architecture and immune infiltration in colocalized regions of interest (ROIs) of 133 invasive tumor front (ITF), 89 tumor niches and 70 target tissues in a total of six paired samples of uADC and nine of uLMS. Microdissected tissue from the ITF was employed for transcriptomic and epigenetic studies in primary and metastatic tumors. Reticulin fiber scaffolding was characterized by a large and loose reticular fiber network in uADC, while dense bundles were found in uLMS. Notably, more similarities between reticulin fibers were observed in paired uLMS then paired uADCs. Transcriptomic and multiplex immunofluorescence-based immune profiling showed a higher abundance of T and B cells in primary tumor and in metastatic uADC than uLMS. Moreover, the epigenetic signature of paired samples in uADCs showed more differences than paired samples in uLMS. Some epigenetic variation was also found between the ITF of metastatic uADC and uLMS. Altogether, our data suggest a correlation between morphological and molecular changes at the ITF and the degree of aggressiveness. The use of DP tools for characterizing reticulin scaffolding and immune cell infiltration at the ITF in paired samples together with information provided by omics analyses in a large cohort will hopefully help validate novel biomarkers of tumor aggressiveness, develop new drugs and improve patient quality of life in a much more efficient way. Frontiers Media S.A. 2022-11-18 /pmc/articles/PMC9716026/ /pubmed/36467415 http://dx.doi.org/10.3389/fcell.2022.1052098 Text en Copyright © 2022 Sonzini, Granados-Aparici, Sanegre, Diaz-Lagares, Diaz-Martin, de Andrea, Eritja, Bao-Caamano, Costa-Fraga, García-Ros, Salguero-Aranda, Davidson, López-López, Melero, Navarro, Ramon y Cajal, de Alava, Matias-Guiu and Noguera. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Cell and Developmental Biology Sonzini, Giorgia Granados-Aparici, Sofia Sanegre, Sabina Diaz-Lagares, Angel Diaz-Martin, Juan de Andrea, Carlos Eritja, Núria Bao-Caamano, Aida Costa-Fraga, Nicolás García-Ros, David Salguero-Aranda, Carmen Davidson, Ben López-López, Rafael Melero, Ignacio Navarro, Samuel Ramon y Cajal, Santiago de Alava, Enrique Matias-Guiu, Xavier Noguera, Rosa Integrating digital pathology with transcriptomic and epigenomic tools for predicting metastatic uterine tumor aggressiveness |
title | Integrating digital pathology with transcriptomic and epigenomic tools for predicting metastatic uterine tumor aggressiveness |
title_full | Integrating digital pathology with transcriptomic and epigenomic tools for predicting metastatic uterine tumor aggressiveness |
title_fullStr | Integrating digital pathology with transcriptomic and epigenomic tools for predicting metastatic uterine tumor aggressiveness |
title_full_unstemmed | Integrating digital pathology with transcriptomic and epigenomic tools for predicting metastatic uterine tumor aggressiveness |
title_short | Integrating digital pathology with transcriptomic and epigenomic tools for predicting metastatic uterine tumor aggressiveness |
title_sort | integrating digital pathology with transcriptomic and epigenomic tools for predicting metastatic uterine tumor aggressiveness |
topic | Cell and Developmental Biology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9716026/ https://www.ncbi.nlm.nih.gov/pubmed/36467415 http://dx.doi.org/10.3389/fcell.2022.1052098 |
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