Single-cell analysis reveals the regulatory role of ECT2 in HPV-driven cervical carcinogenesis process

This study attempted to investigate possible mechanisms of human papillomavirus (HPV) infection from high-grade squamous intraepithelial lesions (HSIL) to cervical cancer (CESC) by combining bulk RNA-seq and scRNA-seq data of CESC. scRNA-seq (GSE208653) and bulk RNA-seq (GSE63514) of CESC were obtained from GEO database. scRNA-seq and clinical data were obtained from the The Cancer Genome Atlas (TCGA) database. mRNA sequencing was performed on cervical samples from HPV-infected patients with histologically normal inflammation (IA), HSIL patients, and CESC patients. Cell-cell communication and hdWGCNA analysis were performed on GSE208653 data. Differentially upregulated genes in HSIL.vs.IA and CESC.vs.HSIL were identified. The intersection of them with the module genes were obtained by hdWGCNA to obtain intersection genes. Immunological analysis was conducted using CIBERSORT in TCGA data. Using MsigDB database and literature research, key signaling pathways were determined, and the relationship between ECT2 and glycolysis metabolism was analyzed. scRNA-seq data analysis identified 13 distinct cell clusters, including B cells, epithelial cells, and cancer stem cells, etc. Cell-cell communication analysis revealed that changes in epithelial cells may affect CESC progression. Key gene ECT2 was obtained through hdWGCNA analysis and clinical sequencing analysis. Validation of multiple datasets revealed that ECT2 may participate in epithelial cell repair during the early inflammatory response to HPV infection through glycolysis, and later glycolysis became a pro-cancer condition, promoting tumor stemness and inhibiting immune activity through lactate accumulation. This study probed into relationships among HPV infection, HSIL, and CESC, and identified potential oncogene ECT2 in epithelial cells and its possible regulatory mechanisms. These findings provided new insights into understanding HPV infection and CESC progression.