Single-Cell RNA Sequencing Reveals Multiple Pathways and the Tumor Microenvironment Could Lead to Chemotherapy Resistance in Cervical Cancer

BackgroundCervical cancer is one of the most common gynecological cancers worldwide. The tumor microenvironment significantly influences the therapeutic response and clinical outcome. However, the complex tumor microenvironment of cervical cancer and the molecular mechanisms underlying chemotherapy...

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Autores principales:	Meijia Gu, Ti He, Yuncong Yuan, Suling Duan, Xin Li, Chao Shen
Formato:	article
Lenguaje:	EN
Publicado:	Frontiers Media S.A. 2021
Materias:	single-cell RNA sequencing cervical cancer tumor microenvironment chemotherapy resistance multiple pathways Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
Acceso en línea:	https://doaj.org/article/0dedb75c36504bc09d48d9aaff905af0
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spelling	oai:doaj.org-article:0dedb75c36504bc09d48d9aaff905af02021-12-01T08:20:36ZSingle-Cell RNA Sequencing Reveals Multiple Pathways and the Tumor Microenvironment Could Lead to Chemotherapy Resistance in Cervical Cancer2234-943X10.3389/fonc.2021.753386https://doaj.org/article/0dedb75c36504bc09d48d9aaff905af02021-11-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fonc.2021.753386/fullhttps://doaj.org/toc/2234-943XBackgroundCervical cancer is one of the most common gynecological cancers worldwide. The tumor microenvironment significantly influences the therapeutic response and clinical outcome. However, the complex tumor microenvironment of cervical cancer and the molecular mechanisms underlying chemotherapy resistance are not well studied. This study aimed to comprehensively analyze cells from pretreated and chemoresistant cervical cancer tissues to generate a molecular census of cell populations.MethodsBiopsy tissues collected from patients with cervical squamous cell carcinoma, cervical adenocarcinoma, and chronic cervicitis were subjected to single-cell RNA sequencing using the 10× Genomics platform. Unsupervised clustering analysis of cells was performed to identify the main cell types, and important cell clusters were reclustered into subpopulations. Gene expression profiles and functional enrichment analysis were used to explore gene expression and functional differences between cell subpopulations in cervicitis and cervical cancer samples and between chemoresistant and chemosensitive samples.ResultsA total of 24,371 cells were clustered into nine separate cell types, including immune and non-immune cells. Differentially expressed genes between chemoresistant and chemosensitive patients enriched in the phosphoinositide 3-kinase (PI3K)/AKT pathway were involved in tumor development, progression, and apoptosis, which might lead to chemotherapy resistance.ConclusionsOur study provides a comprehensive overview of the cancer microenvironment landscape and characterizes its gene expression and functional difference in chemotherapy resistance. Consequently, our study deepens the insights into cervical cancer biology through the identification of gene markers for diagnosis, prognosis, and therapy.Meijia GuTi HeYuncong YuanYuncong YuanSuling DuanXin LiChao ShenChao ShenFrontiers Media S.A.articlesingle-cell RNA sequencingcervical cancertumor microenvironmentchemotherapy resistancemultiple pathwaysNeoplasms. Tumors. Oncology. Including cancer and carcinogensRC254-282ENFrontiers in Oncology, Vol 11 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	single-cell RNA sequencing cervical cancer tumor microenvironment chemotherapy resistance multiple pathways Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
spellingShingle	single-cell RNA sequencing cervical cancer tumor microenvironment chemotherapy resistance multiple pathways Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282 Meijia Gu Ti He Yuncong Yuan Yuncong Yuan Suling Duan Xin Li Chao Shen Chao Shen Single-Cell RNA Sequencing Reveals Multiple Pathways and the Tumor Microenvironment Could Lead to Chemotherapy Resistance in Cervical Cancer
description	BackgroundCervical cancer is one of the most common gynecological cancers worldwide. The tumor microenvironment significantly influences the therapeutic response and clinical outcome. However, the complex tumor microenvironment of cervical cancer and the molecular mechanisms underlying chemotherapy resistance are not well studied. This study aimed to comprehensively analyze cells from pretreated and chemoresistant cervical cancer tissues to generate a molecular census of cell populations.MethodsBiopsy tissues collected from patients with cervical squamous cell carcinoma, cervical adenocarcinoma, and chronic cervicitis were subjected to single-cell RNA sequencing using the 10× Genomics platform. Unsupervised clustering analysis of cells was performed to identify the main cell types, and important cell clusters were reclustered into subpopulations. Gene expression profiles and functional enrichment analysis were used to explore gene expression and functional differences between cell subpopulations in cervicitis and cervical cancer samples and between chemoresistant and chemosensitive samples.ResultsA total of 24,371 cells were clustered into nine separate cell types, including immune and non-immune cells. Differentially expressed genes between chemoresistant and chemosensitive patients enriched in the phosphoinositide 3-kinase (PI3K)/AKT pathway were involved in tumor development, progression, and apoptosis, which might lead to chemotherapy resistance.ConclusionsOur study provides a comprehensive overview of the cancer microenvironment landscape and characterizes its gene expression and functional difference in chemotherapy resistance. Consequently, our study deepens the insights into cervical cancer biology through the identification of gene markers for diagnosis, prognosis, and therapy.
format	article
author	Meijia Gu Ti He Yuncong Yuan Yuncong Yuan Suling Duan Xin Li Chao Shen Chao Shen
author_facet	Meijia Gu Ti He Yuncong Yuan Yuncong Yuan Suling Duan Xin Li Chao Shen Chao Shen
author_sort	Meijia Gu
title	Single-Cell RNA Sequencing Reveals Multiple Pathways and the Tumor Microenvironment Could Lead to Chemotherapy Resistance in Cervical Cancer
title_short	Single-Cell RNA Sequencing Reveals Multiple Pathways and the Tumor Microenvironment Could Lead to Chemotherapy Resistance in Cervical Cancer
title_full	Single-Cell RNA Sequencing Reveals Multiple Pathways and the Tumor Microenvironment Could Lead to Chemotherapy Resistance in Cervical Cancer
title_fullStr	Single-Cell RNA Sequencing Reveals Multiple Pathways and the Tumor Microenvironment Could Lead to Chemotherapy Resistance in Cervical Cancer
title_full_unstemmed	Single-Cell RNA Sequencing Reveals Multiple Pathways and the Tumor Microenvironment Could Lead to Chemotherapy Resistance in Cervical Cancer
title_sort	single-cell rna sequencing reveals multiple pathways and the tumor microenvironment could lead to chemotherapy resistance in cervical cancer
publisher	Frontiers Media S.A.
publishDate	2021
url	https://doaj.org/article/0dedb75c36504bc09d48d9aaff905af0
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Single-Cell RNA Sequencing Reveals Multiple Pathways and the Tumor Microenvironment Could Lead to Chemotherapy Resistance in Cervical Cancer

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