Mapping cellular interactions and communication landscapes in cervical cancer via single-cell transcriptomics

Cervical cancer is among the prevalent gynecological malignancies affecting women worldwide. The diverse cellular populations and their intricate communication patterns within the tumor environment significantly influence cancer development and metastasis. Our research focused on elucidating the cellular diversity, intercellular signaling networks, and underlying molecular processes in cervical cancer tissues via single-cell transcriptomic approaches.

Publicly available single-cell RNA sequencing (scRNA-seq) data for cervical cancer (GSE236738) were re-analysed to delineate the cellular composition and transcriptional programs of the tumour microenvironment. We applied UMAP and t-SNE algorithms for dimensionality reduction, alongside intercellular communication mapping, MIF pathway analysis, temporal trajectory modeling, and pathway enrichment studies, to comprehensively characterize the cellular architecture and molecular profiles within cervical cancer tissues. In addition, paired tumour and adjacent non-tumour cervical tissues from 20 patients were subjected to quantitative real-time PCR and enzyme-linked immunosorbent assay to confirm the transcriptional and protein-level expression of key genes identified by scRNA-seq.

Analysis revealed substantial cellular and molecular diversity within cervical cancer specimens. Ten distinct cellular populations were characterized, including NK lymphocytes, epithelial components, and macrophage subsets, indicating pronounced cellular heterogeneity. Intercellular communication mapping revealed that stromal and epithelial populations are the primary coordinators of cell-to-cell signaling. MIF pathway activity peaked in cancer-associated fibroblasts, which exhibited distinct cell type distributions. Temporal analysis revealed dynamic cellular states and pinpointed critical regulatory elements, including ISG15. Pathway analysis emphasized the importance of neutrophil activity, mitochondrial respiration, and cell adhesion mechanisms in cancer progression. qPCR confirmed that ISG15 and TNFRSF18 were significantly upregulated in tumor tissues, while SDF4 was downregulated and NOC2L showed a moderate increase. ELISA results were consistent with transcript-level findings, demonstrating significant protein overexpression of ISG15 and TNFRSF18 in tumor tissues compared with controls.

Our investigation comprehensively characterized the cellular diversity and molecular features of the cervical cancer microenvironments.