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Single-Cell Sequencing of Malignant Ascites Reveals Transcriptomic Remodeling of the Tumor Microenvironment during the Progression of Epithelial Ovarian Cancer

Epithelial ovarian cancer (EOC) is the main cause of mortality among gynecological malignancies worldwide. Although patients with EOC undergo aggregate treatment, the prognosis is often poor. Peritoneal malignant ascites is a distinguishable clinical feature in EOC patients and plays a pivotal role...

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Autores principales: Li, Yiqun, Wang, Wenjie, Wang, Danyun, Zhang, Liuchao, Wang, Xizhi, He, Jia, Cao, Lei, Li, Kang, Xie, Hongyu
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9778425/
https://www.ncbi.nlm.nih.gov/pubmed/36553542
http://dx.doi.org/10.3390/genes13122276
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author Li, Yiqun
Wang, Wenjie
Wang, Danyun
Zhang, Liuchao
Wang, Xizhi
He, Jia
Cao, Lei
Li, Kang
Xie, Hongyu
author_facet Li, Yiqun
Wang, Wenjie
Wang, Danyun
Zhang, Liuchao
Wang, Xizhi
He, Jia
Cao, Lei
Li, Kang
Xie, Hongyu
author_sort Li, Yiqun
collection PubMed
description Epithelial ovarian cancer (EOC) is the main cause of mortality among gynecological malignancies worldwide. Although patients with EOC undergo aggregate treatment, the prognosis is often poor. Peritoneal malignant ascites is a distinguishable clinical feature in EOC patients and plays a pivotal role in tumor progression and recurrence. The mechanisms of the tumor microenvironment (TME) in ascites in the regulation of tumor progression need to be explored. We comprehensively analyzed the transcriptomes of 4680 single cells from five EOC patients (three diagnostic samples and two recurrent samples) derived from Gene Expression Omnibus (GEO) databases. Batch effects between different samples were removed using an unsupervised deep embedding single-cell cluster algorithm. Subcluster analysis identified the different phenotypes of cells. The transition of a malignant cell state was confirmed using pseudotime analysis. The landscape of TME in malignant ascites was profiled during EOC progression. The transformation of epithelial cancer cells into mesenchymal cells was observed to lead to the emergence of related anti-chemotherapy and immune escape phenotypes. We found the activation of multiple biological pathways with the transition of tumor-associated macrophages and fibroblasts, and we identified the infiltration of CD4(+)CD25(+) T regulatory cells in recurrent samples. The cell adhesion molecules mediated by integrin might be associated with the formation of the tumorsphere. Our study provides novel insights into the remodeling of the TME heterogeneity in malignant ascites during EOC progression, which provides evidence for identifying novel therapeutic targets and promotes the development of ovarian cancer treatment.
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spelling pubmed-97784252022-12-23 Single-Cell Sequencing of Malignant Ascites Reveals Transcriptomic Remodeling of the Tumor Microenvironment during the Progression of Epithelial Ovarian Cancer Li, Yiqun Wang, Wenjie Wang, Danyun Zhang, Liuchao Wang, Xizhi He, Jia Cao, Lei Li, Kang Xie, Hongyu Genes (Basel) Article Epithelial ovarian cancer (EOC) is the main cause of mortality among gynecological malignancies worldwide. Although patients with EOC undergo aggregate treatment, the prognosis is often poor. Peritoneal malignant ascites is a distinguishable clinical feature in EOC patients and plays a pivotal role in tumor progression and recurrence. The mechanisms of the tumor microenvironment (TME) in ascites in the regulation of tumor progression need to be explored. We comprehensively analyzed the transcriptomes of 4680 single cells from five EOC patients (three diagnostic samples and two recurrent samples) derived from Gene Expression Omnibus (GEO) databases. Batch effects between different samples were removed using an unsupervised deep embedding single-cell cluster algorithm. Subcluster analysis identified the different phenotypes of cells. The transition of a malignant cell state was confirmed using pseudotime analysis. The landscape of TME in malignant ascites was profiled during EOC progression. The transformation of epithelial cancer cells into mesenchymal cells was observed to lead to the emergence of related anti-chemotherapy and immune escape phenotypes. We found the activation of multiple biological pathways with the transition of tumor-associated macrophages and fibroblasts, and we identified the infiltration of CD4(+)CD25(+) T regulatory cells in recurrent samples. The cell adhesion molecules mediated by integrin might be associated with the formation of the tumorsphere. Our study provides novel insights into the remodeling of the TME heterogeneity in malignant ascites during EOC progression, which provides evidence for identifying novel therapeutic targets and promotes the development of ovarian cancer treatment. MDPI 2022-12-02 /pmc/articles/PMC9778425/ /pubmed/36553542 http://dx.doi.org/10.3390/genes13122276 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Li, Yiqun
Wang, Wenjie
Wang, Danyun
Zhang, Liuchao
Wang, Xizhi
He, Jia
Cao, Lei
Li, Kang
Xie, Hongyu
Single-Cell Sequencing of Malignant Ascites Reveals Transcriptomic Remodeling of the Tumor Microenvironment during the Progression of Epithelial Ovarian Cancer
title Single-Cell Sequencing of Malignant Ascites Reveals Transcriptomic Remodeling of the Tumor Microenvironment during the Progression of Epithelial Ovarian Cancer
title_full Single-Cell Sequencing of Malignant Ascites Reveals Transcriptomic Remodeling of the Tumor Microenvironment during the Progression of Epithelial Ovarian Cancer
title_fullStr Single-Cell Sequencing of Malignant Ascites Reveals Transcriptomic Remodeling of the Tumor Microenvironment during the Progression of Epithelial Ovarian Cancer
title_full_unstemmed Single-Cell Sequencing of Malignant Ascites Reveals Transcriptomic Remodeling of the Tumor Microenvironment during the Progression of Epithelial Ovarian Cancer
title_short Single-Cell Sequencing of Malignant Ascites Reveals Transcriptomic Remodeling of the Tumor Microenvironment during the Progression of Epithelial Ovarian Cancer
title_sort single-cell sequencing of malignant ascites reveals transcriptomic remodeling of the tumor microenvironment during the progression of epithelial ovarian cancer
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9778425/
https://www.ncbi.nlm.nih.gov/pubmed/36553542
http://dx.doi.org/10.3390/genes13122276
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