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...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2022-11-01
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| Series: | Frontiers in Cell and Developmental Biology |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fcell.2022.1052098/full |
| _version_ | 1828187809465237504 |
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| author | Giorgia Sonzini Sofia Granados-Aparici Sabina Sanegre Sabina Sanegre Angel Diaz-Lagares Angel Diaz-Lagares Juan Diaz-Martin Juan Diaz-Martin Carlos de Andrea Carlos de Andrea Núria Eritja Núria Eritja Aida Bao-Caamano Aida Bao-Caamano Nicolás Costa-Fraga Nicolás Costa-Fraga David García-Ros Carmen Salguero-Aranda Carmen Salguero-Aranda Ben Davidson Ben Davidson Rafael López-López Rafael López-López Ignacio Melero Ignacio Melero Samuel Navarro Samuel Navarro Santiago Ramon y Cajal Santiago Ramon y Cajal Enrique de Alava Enrique de Alava Xavier Matias-Guiu Xavier Matias-Guiu Rosa Noguera Rosa Noguera |
| author_facet | Giorgia Sonzini Sofia Granados-Aparici Sabina Sanegre Sabina Sanegre Angel Diaz-Lagares Angel Diaz-Lagares Juan Diaz-Martin Juan Diaz-Martin Carlos de Andrea Carlos de Andrea Núria Eritja Núria Eritja Aida Bao-Caamano Aida Bao-Caamano Nicolás Costa-Fraga Nicolás Costa-Fraga David García-Ros Carmen Salguero-Aranda Carmen Salguero-Aranda Ben Davidson Ben Davidson Rafael López-López Rafael López-López Ignacio Melero Ignacio Melero Samuel Navarro Samuel Navarro Santiago Ramon y Cajal Santiago Ramon y Cajal Enrique de Alava Enrique de Alava Xavier Matias-Guiu Xavier Matias-Guiu Rosa Noguera Rosa Noguera |
| author_sort | Giorgia Sonzini |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-04-12T07:41:52Z |
| format | Article |
| id | doaj.art-1debe2f1f3eb466fb9188e4c9d95f9d3 |
| institution | Directory Open Access Journal |
| issn | 2296-634X |
| language | English |
| last_indexed | 2024-04-12T07:41:52Z |
| publishDate | 2022-11-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Cell and Developmental Biology |
| spelling | doaj.art-1debe2f1f3eb466fb9188e4c9d95f9d32022-12-22T03:41:48ZengFrontiers Media S.A.Frontiers in Cell and Developmental Biology2296-634X2022-11-011010.3389/fcell.2022.10520981052098Integrating digital pathology with transcriptomic and epigenomic tools for predicting metastatic uterine tumor aggressivenessGiorgia Sonzini0Sofia Granados-Aparici1Sabina Sanegre2Sabina Sanegre3Angel Diaz-Lagares4Angel Diaz-Lagares5Juan Diaz-Martin6Juan Diaz-Martin7Carlos de Andrea8Carlos de Andrea9Núria Eritja10Núria Eritja11Aida Bao-Caamano12Aida Bao-Caamano13Nicolás Costa-Fraga14Nicolás Costa-Fraga15David García-Ros16Carmen Salguero-Aranda17Carmen Salguero-Aranda18Ben Davidson19Ben Davidson20Rafael López-López21Rafael López-López22Ignacio Melero23Ignacio Melero24Samuel Navarro25Samuel Navarro26Santiago Ramon y Cajal27Santiago Ramon y Cajal28Enrique de Alava29Enrique de Alava30Xavier Matias-Guiu31Xavier Matias-Guiu32Rosa Noguera33Rosa Noguera34Department of Pathology, Medical School, University of Valencia-INCLIVA, Valencia, SpainDepartment of Pathology, Medical School, University of Valencia-INCLIVA, Valencia, SpainDepartment of Pathology, Medical School, University of Valencia-INCLIVA, Valencia, SpainCancer CIBER (CIBERONC), Madrid, SpainCancer CIBER (CIBERONC), Madrid, SpainEpigenomics Unit, Cancer Epigenomics, Translational Medical Oncology Group (Oncomet), Health Research Institute of Santiago (IDIS), University Clinical Hospital of Santiago (CHUS/SERGAS), Santiago de Compostela, SpainCancer CIBER (CIBERONC), Madrid, SpainInstitute of Biomedicine of Sevilla (IBiS), Virgen del Rocio University Hospital/CSIC/University of Sevilla, Seville, SpainCancer CIBER (CIBERONC), Madrid, SpainClínica Universidad de Navarra, University of Navarra, Pamplona, SpainCancer CIBER (CIBERONC), Madrid, SpainInstitut de Recerca Biomèdica de LLeida (IRBLLEIDA), Institut d'Investigació Biomèdica de Bellvitge (IDIBELL), Department of Pathology, Hospital U Arnau de Vilanova and Hospital U de Bellvitge, University of Lleida - University of Barcelona, Barcelona, SpainEpigenomics Unit, Cancer Epigenomics, Translational Medical Oncology Group (Oncomet), Health Research Institute of Santiago (IDIS), University Clinical Hospital of Santiago (CHUS/SERGAS), Santiago de Compostela, SpainUniversidad de Santiago de Compostela (USC), Santiago de Compostela, SpainEpigenomics Unit, Cancer Epigenomics, Translational Medical Oncology Group (Oncomet), Health Research Institute of Santiago (IDIS), University Clinical Hospital of Santiago (CHUS/SERGAS), Santiago de Compostela, SpainUniversidad de Santiago de Compostela (USC), Santiago de Compostela, SpainClínica Universidad de Navarra, University of Navarra, Pamplona, SpainCancer CIBER (CIBERONC), Madrid, SpainInstitute of Biomedicine of Sevilla (IBiS), Virgen del Rocio University Hospital/CSIC/University of Sevilla, Seville, SpainInstitute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, NorwayDepartment of Pathology, Oslo University Hospital, Norwegian Radium Hospital, Oslo, NorwayCancer CIBER (CIBERONC), Madrid, Spain0Roche-Chus Joint Unit, Translational Medical Oncology Group (Oncomet), Health Research Institute of Santiago (IDIS), Santiago de Compostela, SpainCancer CIBER (CIBERONC), Madrid, SpainClínica Universidad de Navarra, University of Navarra, Pamplona, SpainDepartment of Pathology, Medical School, University of Valencia-INCLIVA, Valencia, SpainCancer CIBER (CIBERONC), Madrid, SpainCancer CIBER (CIBERONC), Madrid, Spain1Department of Pathology, Vall d'Hebron University Hospital, Autonoma University of Barcelona, Barcelona, SpainCancer CIBER (CIBERONC), Madrid, SpainInstitute of Biomedicine of Sevilla (IBiS), Virgen del Rocio University Hospital/CSIC/University of Sevilla, Seville, SpainCancer CIBER (CIBERONC), Madrid, SpainInstitut de Recerca Biomèdica de LLeida (IRBLLEIDA), Institut d'Investigació Biomèdica de Bellvitge (IDIBELL), Department of Pathology, Hospital U Arnau de Vilanova and Hospital U de Bellvitge, University of Lleida - University of Barcelona, Barcelona, SpainDepartment of Pathology, Medical School, University of Valencia-INCLIVA, Valencia, SpainCancer CIBER (CIBERONC), Madrid, SpainThe 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.https://www.frontiersin.org/articles/10.3389/fcell.2022.1052098/fulluterine adenocarcinomauterine leiomyosarcomalung metastasisdigital pathologyinvasive tumor frontmultiplex immunofluorescence |
| spellingShingle | Giorgia Sonzini Sofia Granados-Aparici Sabina Sanegre Sabina Sanegre Angel Diaz-Lagares Angel Diaz-Lagares Juan Diaz-Martin Juan Diaz-Martin Carlos de Andrea Carlos de Andrea Núria Eritja Núria Eritja Aida Bao-Caamano Aida Bao-Caamano Nicolás Costa-Fraga Nicolás Costa-Fraga David García-Ros Carmen Salguero-Aranda Carmen Salguero-Aranda Ben Davidson Ben Davidson Rafael López-López Rafael López-López Ignacio Melero Ignacio Melero Samuel Navarro Samuel Navarro Santiago Ramon y Cajal Santiago Ramon y Cajal Enrique de Alava Enrique de Alava Xavier Matias-Guiu Xavier Matias-Guiu Rosa Noguera Rosa Noguera Integrating digital pathology with transcriptomic and epigenomic tools for predicting metastatic uterine tumor aggressiveness Frontiers in Cell and Developmental Biology uterine adenocarcinoma uterine leiomyosarcoma lung metastasis digital pathology invasive tumor front multiplex immunofluorescence |
| 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 | uterine adenocarcinoma uterine leiomyosarcoma lung metastasis digital pathology invasive tumor front multiplex immunofluorescence |
| url | https://www.frontiersin.org/articles/10.3389/fcell.2022.1052098/full |
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