Single-cell and bulk RNA sequencing reveal ligands and receptors associated with worse overall survival in serous ovarian cancer
Autor(a) principal: | |
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Data de Publicação: | 2022 |
Outros Autores: | , , , , , , , |
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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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 |
|
_version_ |
1808129589090713600 |