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

Meijia Gu,Xin Li,Yuncong Yuan,Suling Duan,Ti He,Chao Shen

doi:10.3389/fonc.2021.753386

Meijia Gu, Xin Li + Show 4 more

Open Access

https://doi.org/10.3389/fonc.2021.753386

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Abstract

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.

Highlights

As the fourth most common gynecological malignant tumor, cervical cancer is a leading cause of cancer-related deaths among women and poses a serious threat to the health of women worldwide [1]
Our study provides novel insights into the heterogeneity of cervical cancer at the single-cell level and will serve as a valuable resource for understanding chemotherapy resistance mechanisms in tumor progression
The main cell types were identified based on gene expression patterns obtained using dimensionality reduction and unsupervised cell clustering with the described Seurat pipeline

Summary

Introduction

As the fourth most common gynecological malignant tumor, cervical cancer is a leading cause of cancer-related deaths among women and poses a serious threat to the health of women worldwide [1]. Paclitaxel, cisplatin, carboplatin, or a combination of these agents is the front-line treatment for cervical cancer [2]. In actual clinical treatment, tumor cells often develop resistance. Cervical cancer is one of the most common gynecological cancers worldwide. The tumor microenvironment significantly influences the therapeutic response and clinical outcome. 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

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