Introduction The establishment of a proangiogenic phenotype and epithelial-mesenchymal transition (EMT) are regarded as prerequisites for activation of invasive growth and dissemination of malignant cells in epithelial tumors. Various borderline conditions, as for example a transition between intraepithelial neoplasia and microcarcinoma, can be the source of critical factors that act as driving forces for further tumor spread, but in the case of cervical cancer these issues remain poorly studied.

Methods RNA-sequencing and bioinformatics analysis were used to compare transcriptomes and signaling pathways activation profiles in HPV-positive preinvasive neoplastic lesions and early-stage invasive cervical carcinoma samples obtained from patients. Flow cytometry was applied to evaluate the expression of three key lymphangiogenesis and EMT markers (VEGFR3, MET, and SLUG) in epithelial cells derived from enzymatically treated tissue specimens.

Results The differentially expressed genes were screened for angiogenesis, lymphangiogenesis, EMT, and invasion regulatory factors and subsequent pathway analysis confirmed enrichment for angiogenesis, epithelial organization, and cell guidance pathways at transition from intraepithelial neoplasia to invasive carcinoma and suggested inflammatory antiviral response-associated pathways to be critically implicated in initiation of invasive growth of cervical cancer. Cell-phenotype-specific expression pattern for VEGFR3, MET, and SLUG was revealed which appeared to be correlated with the amount of tumor-infiltrating lymphocytes at the earliest stages of cancer progression.

Conclusion These findings extend the existing knowledge about driving forces of angiogenesis and metastasis in cervical cancer and may be useful for developing new treatments. The study was supported by the state assignment of the Ministry of Science and Higher Education, project No.0752-2020-0007 (AAAA-A20-120070290151-6).