Single-cell transcriptomics reveals the landscape of intra-tumoral heterogeneity and transcriptional activities of ECs in CC

Abstract

Cervical cancer (CC) is the fourth leading cause of deaths in gynecological malignancies. Although the etiology of CC has been extensively investigated, the exact pathogenesis of CC remains incomplete. Recently, single-cell technologies demonstrated advantages in exploring intra-tumoral diversification among various tumor cells. However, single-cell transcriptome analysis (single-cell RNA sequencing [scRNA-seq]) of CC cells and microenvironment has not been conducted. In this study, a total of 20,938 cells from CC and adjacent normal tissues were examined by scRNA-seq. We identified four tumor cell subpopulations in tumor cells, which had specific signature genes with different biological functions and presented different prognoses. Among them, we identified a subset of cancer stem cells (CSCs) that was related to the developmental hierarchy of tumor progression. Then, we compared the expressive differences between tumor-derived endothelial cells (TECs) and normal ECs (NECs) and revealed higher expression of several metabolism-related genes in TECs. Then, we explored the potential biological function of ECs in vascularization and found several marker genes, which played a prior role in connections between cancer cells and ECs. Our findings provide valuable resources for deciphering the intra-tumoral heterogeneity of CC and uncover the developmental procedure of ECs, which paves the way for CC therapy.

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

“…To the best of our knowledge, this is one of the first few studies to comprehensively characterize a single-cell atlas of cervical cancer patients in China and worldwide (60).…”

Functional New Transcription Factors (TFs) Associated with Cervical Cancer

“…10x genomic single-cell RNA-sequencing files of cervical cancer and normal tissue: GSE168652 (GSM5155196 and GSM5155197) were downloaded from NCBI GEO [ 33 ]. The expression matrix was loaded into R and analyzed by Seurat package (version 4.0.3) [ 34 ].…”

A New Antitumor Direction: Tumor-Specific Endothelial Cells

“…TAGLN2, KLF5, STAT1 and STAT2 (7). ScRNA sequencing revealed that 2590 genes were differentially expressed between TECs isolated from human hepatocellular carcinoma and NECs isolated from normal liver tissues (61).…”

“…Initial hypotheses suggested that TECs were genetically stable normal somatic cells that were not prone to mutation and drug resistance and remained consistent in various tumors, which would allow multiple types of cancer to be treated by a single antiangiogenic drug (5). However, in recent years, many researchers have found that TECs are not ordinary somatic cells but rather are heterogeneous in many aspects relative to normal endothelial cells (NECs), which contradicts previous assumptions (6,7). Therefore, the study of TECs will provide targets or directions for tumor therapy.…”