RT Journal Article
T1 Integrating digital pathology with transcriptomic and epigenomic tools for predicting metastatic uterine tumor aggressiveness
A1 Sonzini, Giorgia
A1 Granados-Aparici, Sofia
A1 Sanegre, Sabina
A1 Diaz-Lagares, Angel
A1 Diaz-Martin, Juan
A1 de Andrea, Carlos
A1 Eritja, Nuria
A1 Bao-Caamano, Aida
A1 Costa-Fraga, Nicolas
A1 Garcia-Ros, David
A1 Salguero-Aranda, Carmen
A1 Davidson, Ben
A1 Lopez-Lopez, Rafael
A1 Melero, Ignacio
A1 Navarro, Samuel
A1 Ramon y Cajal, Santiago
A1 de Alava, Enrique
A1 Matias-Guiu, Xavier
A1 Noguera, Rosa
K1 uterine adenocarcinoma
K1 uterine leiomyosarcoma
K1 lung metastasis
K1 digital pathology
K1 invasive tumor front
K1 multiplex immunofluorescence
K1 transcriptomics
K1 methylomics
K1 Collagen
K1 Defines
K1 Cancer
AB 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.
PB Frontiers media sa
SN 2296-634X
YR 2022
FD 2022-11-18
LK http://hdl.handle.net/10668/20539
UL http://hdl.handle.net/10668/20539
LA en
DS RISalud
RD Apr 11, 2025