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| Home > Articles > Published articles > Integrating digital pathology with transcriptomic and epigenomic tools for predicting metastatic uterine tumor aggressiveness |
| Home > Articles > Published articles > Integrating digital pathology with transcriptomic and epigenomic tools for predicting metastatic uterine tumor aggressiveness |
(Hospital Clínico Universitario (Santiago de Compostela, Galícia)) (Universidade de Santiago de Compostela) (Instituto de Investigación Sanitaria de Santiago (IDIS)) (Universitat Autònoma de Barcelona) (Hospital Universitario Virgen del Rocío (Sevilla, Andalusia))| Date: | 2022 |
| Abstract: | 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. |
| Grants: | Instituto de Salud Carlos III PI17/01558 Ministerio de Economía, Industria y Competitividad CB16/12/00484 Instituto de Salud Carlos III CB16/12/0328 Instituto de Salud Carlos III CB16/12/00363 Instituto de Salud Carlos III CB16/12/00364 Instituto de Salud Carlos III CB16/12/00481 Instituto de Salud Carlos III CB16/12/00231 Instituto de Salud Carlos III FI19/00240 |
| Rights: | Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.  |
| Language: | Anglès |
| Document: | Article ; recerca ; Versió publicada |
| Subject: | Uterine adenocarcinoma ; Uterine leiomyosarcoma ; Lung metastasis ; Digital pathology ; Invasive tumor front ; Multiplex immunofluorescence ; Transcriptomics ; Methylomics |
| Published in: | Frontiers in Cell and Developmental Biology, Vol. 10 (november 2022) , ISSN 2296-634X |
