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

Detalhes bibliográficos
Autor(a) principal: Carvalho, Robson Francisco [UNESP]
Data de Publicação: 2022
Outros Autores: do Canto, Luisa Matos, Abildgaard, Cecilie, Aagaard, Mads Malik, Tronhjem, Monica Søgaard, Waldstrøm, Marianne, Jensen, Lars Henrik, Steffensen, Karina Dahl, Rogatto, Silvia Regina
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Repositório Institucional da UNESP
Texto Completo: http://dx.doi.org/10.1186/s12964-022-00991-4
http://hdl.handle.net/11449/249345
Resumo: Background: 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.].
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spelling Single-cell and bulk RNA sequencing reveal ligands and receptors associated with worse overall survival in serous ovarian cancerCancer-associated fibroblastsCell–cell communicationOrganoidsSerous ovarian cancerSingle-cell RNA-sequencingBackground: 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.].Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)Department of Clinical Genetics University Hospital of Southern DenmarkInstitute of Regional Health Research University of Southern DenmarkDepartment of Structural and Functional Biology - Institute of Bioscience São Paulo State University (UNESP), 18.618-689Department of Oncology University Hospital of Southern DenmarkDanish Colorectal Cancer Center SouthDepartment of Clinical Pathology University Hospital of Southern DenmarkDepartment of Structural and Functional Biology - Institute of Bioscience São Paulo State University (UNESP), 18.618-689CAPES: 88887.310463/2018-00University Hospital of Southern DenmarkUniversity of Southern DenmarkUniversidade Estadual Paulista (UNESP)Danish Colorectal Cancer Center SouthCarvalho, Robson Francisco [UNESP]do Canto, Luisa MatosAbildgaard, CecilieAagaard, Mads MalikTronhjem, Monica SøgaardWaldstrøm, MarianneJensen, Lars HenrikSteffensen, Karina DahlRogatto, Silvia Regina2023-07-29T15:13:34Z2023-07-29T15:13:34Z2022-12-01info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articlehttp://dx.doi.org/10.1186/s12964-022-00991-4Cell Communication and Signaling, v. 20, n. 1, 2022.1478-811Xhttp://hdl.handle.net/11449/24934510.1186/s12964-022-00991-42-s2.0-85141464842Scopusreponame:Repositório Institucional da UNESPinstname:Universidade Estadual Paulista (UNESP)instacron:UNESPengCell Communication and Signalinginfo:eu-repo/semantics/openAccess2023-07-29T15:13:34Zoai:repositorio.unesp.br:11449/249345Repositório InstitucionalPUBhttp://repositorio.unesp.br/oai/requestopendoar:29462024-08-06T00:08:22.665421Repositório Institucional da UNESP - Universidade Estadual Paulista (UNESP)false
dc.title.none.fl_str_mv Single-cell and bulk RNA sequencing reveal ligands and receptors associated with worse overall survival in serous ovarian cancer
title Single-cell and bulk RNA sequencing reveal ligands and receptors associated with worse overall survival in serous ovarian cancer
spellingShingle Single-cell and bulk RNA sequencing reveal ligands and receptors associated with worse overall survival in serous ovarian cancer
Carvalho, Robson Francisco [UNESP]
Cancer-associated fibroblasts
Cell–cell communication
Organoids
Serous ovarian cancer
Single-cell RNA-sequencing
title_short Single-cell and bulk RNA sequencing reveal ligands and receptors associated with worse overall survival in serous ovarian cancer
title_full Single-cell and bulk RNA sequencing reveal ligands and receptors associated with worse overall survival in serous ovarian cancer
title_fullStr Single-cell and bulk RNA sequencing reveal ligands and receptors associated with worse overall survival in serous ovarian cancer
title_full_unstemmed Single-cell and bulk RNA sequencing reveal ligands and receptors associated with worse overall survival in serous ovarian cancer
title_sort Single-cell and bulk RNA sequencing reveal ligands and receptors associated with worse overall survival in serous ovarian cancer
author Carvalho, Robson Francisco [UNESP]
author_facet Carvalho, Robson Francisco [UNESP]
do Canto, Luisa Matos
Abildgaard, Cecilie
Aagaard, Mads Malik
Tronhjem, Monica Søgaard
Waldstrøm, Marianne
Jensen, Lars Henrik
Steffensen, Karina Dahl
Rogatto, Silvia Regina
author_role author
author2 do Canto, Luisa Matos
Abildgaard, Cecilie
Aagaard, Mads Malik
Tronhjem, Monica Søgaard
Waldstrøm, Marianne
Jensen, Lars Henrik
Steffensen, Karina Dahl
Rogatto, Silvia Regina
author2_role author
author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv University Hospital of Southern Denmark
University of Southern Denmark
Universidade Estadual Paulista (UNESP)
Danish Colorectal Cancer Center South
dc.contributor.author.fl_str_mv Carvalho, Robson Francisco [UNESP]
do Canto, Luisa Matos
Abildgaard, Cecilie
Aagaard, Mads Malik
Tronhjem, Monica Søgaard
Waldstrøm, Marianne
Jensen, Lars Henrik
Steffensen, Karina Dahl
Rogatto, Silvia Regina
dc.subject.por.fl_str_mv Cancer-associated fibroblasts
Cell–cell communication
Organoids
Serous ovarian cancer
Single-cell RNA-sequencing
topic Cancer-associated fibroblasts
Cell–cell communication
Organoids
Serous ovarian cancer
Single-cell RNA-sequencing
description Background: 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.].
publishDate 2022
dc.date.none.fl_str_mv 2022-12-01
2023-07-29T15:13:34Z
2023-07-29T15:13:34Z
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
dc.type.driver.fl_str_mv info:eu-repo/semantics/article
format article
status_str publishedVersion
dc.identifier.uri.fl_str_mv http://dx.doi.org/10.1186/s12964-022-00991-4
Cell Communication and Signaling, v. 20, n. 1, 2022.
1478-811X
http://hdl.handle.net/11449/249345
10.1186/s12964-022-00991-4
2-s2.0-85141464842
url http://dx.doi.org/10.1186/s12964-022-00991-4
http://hdl.handle.net/11449/249345
identifier_str_mv Cell Communication and Signaling, v. 20, n. 1, 2022.
1478-811X
10.1186/s12964-022-00991-4
2-s2.0-85141464842
dc.language.iso.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv Cell Communication and Signaling
dc.rights.driver.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.source.none.fl_str_mv Scopus
reponame:Repositório Institucional da UNESP
instname:Universidade Estadual Paulista (UNESP)
instacron:UNESP
instname_str Universidade Estadual Paulista (UNESP)
instacron_str UNESP
institution UNESP
reponame_str Repositório Institucional da UNESP
collection Repositório Institucional da UNESP
repository.name.fl_str_mv Repositório Institucional da UNESP - Universidade Estadual Paulista (UNESP)
repository.mail.fl_str_mv
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