Proteomic Analysis of Low-Grade, Early-Stage Endometrial Carcinoma Reveals New Dysregulated Pathways Associated with Cell Death and Cell Signaling.
SLIT/ROBO
endometrial cancer
ferroptosis
immune microenvironment
low grade
necroptosis
pathways
proteomics
Journal
Cancers
ISSN: 2072-6694
Titre abrégé: Cancers (Basel)
Pays: Switzerland
ID NLM: 101526829
Informations de publication
Date de publication:
14 Feb 2021
14 Feb 2021
Historique:
received:
16
12
2020
revised:
28
01
2021
accepted:
09
02
2021
entrez:
6
3
2021
pubmed:
7
3
2021
medline:
7
3
2021
Statut:
epublish
Résumé
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.
Identifiants
pubmed: 33672863
pii: cancers13040794
doi: 10.3390/cancers13040794
pmc: PMC7917913
pii:
doi:
Types de publication
Journal Article
Langues
eng
Subventions
Organisme : Instituto de Salud Carlos III
ID : PI17/01723
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