Single-cell and bulk RNA sequencing reveal ligands and receptors associated with worse overall survival in serous ovarian cancer

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Autor(es): dc.contributorUniversity Hospital of Southern Denmark-
Autor(es): dc.contributorUniversity of Southern Denmark-
Autor(es): dc.contributorUniversidade Estadual Paulista (UNESP)-
Autor(es): dc.contributorDanish Colorectal Cancer Center South-
Autor(es): dc.creatorCarvalho, Robson Francisco-
Autor(es): dc.creatordo Canto, Luisa Matos-
Autor(es): dc.creatorAbildgaard, Cecilie-
Autor(es): dc.creatorAagaard, Mads Malik-
Autor(es): dc.creatorTronhjem, Monica Søgaard-
Autor(es): dc.creatorWaldstrøm, Marianne-
Autor(es): dc.creatorJensen, Lars Henrik-
Autor(es): dc.creatorSteffensen, Karina Dahl-
Autor(es): dc.creatorRogatto, Silvia Regina-
Data de aceite: dc.date.accessioned2025-08-21T23:39:41Z-
Data de disponibilização: dc.date.available2025-08-21T23:39:41Z-
Data de envio: dc.date.issued2023-07-29-
Data de envio: dc.date.issued2023-07-29-
Data de envio: dc.date.issued2022-11-30-
Fonte completa do material: dc.identifierhttp://dx.doi.org/10.1186/s12964-022-00991-4-
Fonte completa do material: dc.identifierhttp://hdl.handle.net/11449/249345-
Fonte: dc.identifier.urihttp://educapes.capes.gov.br/handle/11449/249345-
Descrição: dc.descriptionBackground: Serous ovarian carcinoma is the most frequent histological subgroup of ovarian cancer and the leading cause of death among gynecologic tumors. The tumor microenvironment and cancer-associated fibroblasts (CAFs) have a critical role in the origin and progression of cancer. We comprehensively characterized the crosstalk between CAFs and ovarian cancer cells from malignant fluids to identify specific ligands and receptors mediating intercellular communications and disrupted pathways related to prognosis and therapy response. Methods: Malignant fluids of serous ovarian cancer, including tumor-derived organoids, CAFs-enriched (eCAFs), and malignant effusion cells (no cultured) paired with normal ovarian tissues, were explored by RNA-sequencing. These data were integrated with single-cell RNA-sequencing data of ascites from ovarian cancer patients. The most relevant ligand and receptor interactions were used to identify differentially expressed genes with prognostic values in ovarian cancer. Results: CAF ligands and epithelial cancer cell receptors were enriched for PI3K-AKT, focal adhesion, and epithelial-mesenchymal transition signaling pathways. Collagens, MIF, MDK, APP, and laminin were detected as the most significant signaling, and the top ligand-receptor interactions THBS2/THBS3 (CAFs)—CD47 (cancer cells), MDK (CAFs)—NCL/SDC2/SDC4 (cancer cells) as potential therapeutic targets. Interestingly, 34 genes encoding receptors and ligands of the PI3K pathway were associated with the outcome, response to treatment, and overall survival in ovarian cancer. Up-regulated genes from this list consistently predicted a worse overall survival (hazard ratio > 1.0 and log-rank P < 0.05) in two independent validation cohorts. Conclusions: This study describes critical signaling pathways, ligands, and receptors involved in the communication between CAFs and cancer cells that have prognostic and therapeutic significance in ovarian cancer. [MediaObject not available: see fulltext.].-
Descrição: dc.descriptionCoordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)-
Descrição: dc.descriptionDepartment of Clinical Genetics University Hospital of Southern Denmark-
Descrição: dc.descriptionInstitute of Regional Health Research University of Southern Denmark-
Descrição: dc.descriptionDepartment of Structural and Functional Biology - Institute of Bioscience São Paulo State University (UNESP), 18.618-689-
Descrição: dc.descriptionDepartment of Oncology University Hospital of Southern Denmark-
Descrição: dc.descriptionDanish Colorectal Cancer Center South-
Descrição: dc.descriptionDepartment of Clinical Pathology University Hospital of Southern Denmark-
Descrição: dc.descriptionDepartment of Structural and Functional Biology - Institute of Bioscience São Paulo State University (UNESP), 18.618-689-
Descrição: dc.descriptionCAPES: 88887.310463/2018-00-
Idioma: dc.languageen-
Relação: dc.relationCell Communication and Signaling-
???dc.source???: dc.sourceScopus-
Palavras-chave: dc.subjectCancer-associated fibroblasts-
Palavras-chave: dc.subjectCell–cell communication-
Palavras-chave: dc.subjectOrganoids-
Palavras-chave: dc.subjectSerous ovarian cancer-
Palavras-chave: dc.subjectSingle-cell RNA-sequencing-
Título: dc.titleSingle-cell and bulk RNA sequencing reveal ligands and receptors associated with worse overall survival in serous ovarian cancer-
Tipo de arquivo: dc.typelivro digital-
Aparece nas coleções:Repositório Institucional - Unesp

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