Proteomic analysis of low-grade, early-stage endometrial carcinoma reveals new dysregulated pathways associated with cell death and cell signaling
AuthorLópez-Janeiro, Álvaro; Ruz-Caracuel, Ignacio; Ramón-Patino, Jorge L.; Ríos, Vivian De Los; Esparza, María Villalba; Berjón, Alberto; Yébenes, Laura; Hernández, Alicia; Masetto, Ivan; Kadioglu, Ece; Goubert, Virginie; Heredia-Soto, Victoria; Barderas, Rodrigo; Casal, José Ignacio; de Andrea, Carlos E.; Redondo Sánchez, Andrés; Mendiola, Marta; Peláez-García, Alberto; Hardisson Hernáez, David Alonso
EntityUAM. Departamento de Anatomía Patológica
10.3390/cancers13040794Cancers 13.4 (2021): 794
Funded byThis research was funded by the Instituto de Salud Carlos III (ISCIII) (PI17/01723), cofinanced by the European Development Regional Fund “A way to achieve Europe” (FEDER)
ProjectGobierno de España. PI17/01723
SubjectsEndometrial cancer; Ferrop-tosis; Immune microenvironment; Low grade; Necroptosis; Pathways; Proteomics; SLIT/ROBO; Medicina
Rights© 2021 by the authors
Esta obra está bajo una Licencia Creative Commons Atribución 4.0 Internacional.
Low-grade, early-stage endometrial carcinoma (EC) is the most frequent malignant tumor of the uterine corpus. However, the molecular alterations that underlie these tumors are far from being fully understood. The purpose of this study is to describe dysregulated molecular pathways from EC patients. Sixteen samples of tumor tissue and paired healthy controls were collected and both were subjected to mass spectrometry (MS)/MS proteomic analysis. Gene ontology and pathway analysis was performed to discover dysregulated pathways and/or proteins using different databases and bioinformatic tools. Dysregulated pathways were cross-validated in an independent external cohort. Cell signaling, immune response, and cell death-associated pathways were robustly identified. The SLIT/ROBO signaling pathway demonstrated dysregulation at the proteomic and transcriptomic level. Necroptosis and ferroptosis were cell death-associated processes aberrantly regulated, in addition to apoptosis. Immune response-associated pathways showed a dominance of innate immune responses. Tumor immune infiltrates measured by immunofluorescence demonstrated diverse lymphoid and myeloid populations. Our results suggest a role of SLIT/ROBO, necroptosis, and ferroptosis, as well as a prominent role of innate immune response in low-grade, early-stage EC. These results could guide future research in this group of tumors
Google Scholar:López-Janeiro, Álvaro - Ruz-Caracuel, Ignacio - Ramón-Patino, Jorge L. - Ríos, Vivian De Los - Esparza, María Villalba - Berjón, Alberto - Yébenes, Laura - Hernández, Alicia - Masetto, Ivan - Kadioglu, Ece - Goubert, Virginie - Heredia-Soto, Victoria - Barderas, Rodrigo - Casal, José Ignacio - de Andrea, Carlos E. - Redondo Sánchez, Andrés - Mendiola, Marta - Peláez-García, Alberto - Hardisson Hernáez, David Alonso
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Proteomic analysis of low-grade, early-stage endometrial carcinoma reveals new dysregulated pathways associated with cell death and cell signaling López-Janeiro, Álvaro; Ruz-Caracuel, Ignacio; Ramón-Patino, Jorge L.; Ríos, Vivian De Los; Esparza, María Villalba; Berjón, Alberto; Yébenes, Laura; Hernández Gutiérrez, María Alicia; Masetto, Ivan; Kadioglu, Ece; Goubert, Virginie; Heredia-Soto, Victoria; Barderas, Rodrigo; Casal, José Ignacio; de Andrea, Carlos E.; Redondo Sánchez, Andrés; Mendiola, Marta; Peláez-García, Alberto; Hardisson Hernáez, David Alonso
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