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.
© 2022. The Author(s).