Single-cell transcriptomics reveals cellular heterogeneity and molecular stratification of cervical cancer

• Published in: Communications biology Vol. 5; no. 1; pp. 1208 - 10
• Main Authors: Li, Chunbo, Wu, Hao, Guo, Luopei, Liu, Danyang, Yang, Shimin, Li, Shengli, Hua, Keqin
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 10.11.2022; Nature Publishing Group; Nature Portfolio
• Subjects: 38/39; 38/91; 631/114/2164; 631/67/1517/1371; 631/67/327; Biology; Biomedical and Life Sciences; Cancer-Associated Fibroblasts - pathology; CD8 antigen; Cervical cancer; Cervix; Female; Fibroblasts; Humans; Hypoxia; Inflammation; Life Sciences; Lymphocytes T; Malignancy; Medical prognosis; Prognosis; Ribonucleic acid; RNA; Single-Cell Analysis - methods; Transcriptome; Transcriptomes; Transcriptomics; Tumors; Uterine Cervical Neoplasms - genetics; Uterine Cervical Neoplasms - pathology
• ISSN: 2399-3642; 2399-3642
• DOI: 10.1038/s42003-022-04142-w

Cervical cancer (CC) is the most common gynecological malignancy, whose cellular heterogeneity has not been fully understood. Here, we performed single-cell RNA sequencing (scRNA-seq) to survey the transcriptomes of 57,669 cells derived from three CC tumors with paired normal adjacent non-tumor (NAT) samples. Single-cell transcriptomics analysis revealed extensive heterogeneity in malignant cells of human CCs, wherein epithelial subpopulation exhibited different genomic and transcriptomic signatures. We also identified cancer-associated fibroblasts (CAFs) that may promote tumor progression of CC, and further distinguished inflammatory CAF (iCAF) and myofibroblastic CAF (myCAF). CD8 + T cell diversity revealed both proliferative ( MKI67 + ) and non-cycling exhausted ( PDCD1 + ) subpopulations at the end of the trajectory path. We used the epithelial signature genes derived from scRNA-seq to deconvolute bulk RNA-seq data of CC, identifying four different CC subtypes, namely hypoxia (S-H subtype), proliferation (S-P subtype), differentiation (S-D subtype), and immunoactive (S-I subtype) subtype. The S-H subtype showed the worst prognosis, while CC patients of the S-I subtype had the longest overall survival time. Our results lay the foundation for precision prognostic and therapeutic stratification of CC. Single-cell RNA sequencing of cervical cancer reveals four different cancer subtypes and provides information on populations of cancer-associated fibroblasts as well as CD8+ T cell diversity.