Profiling of Lymphovascular Space Invasion in Cervical Cancer Revealed PI3K/Akt Signaling Pathway Overactivation and Heterogenic Tumor-Immune Microenvironments

Abstract

Lymphovascular space invasion (LVSI) is the presence of tumor emboli in the endothelial-lined space at the tumor body’s invasive edge. LVSI is one of three Sedlis criteria components—a prognostic tool for early cervical cancer (CC)—essential for indicating poor prognosis, such as lymph node metastasis, distant metastasis, or shorter survival rate. Despite its clinical significance, an in-depth comprehension of the molecular mechanisms or immune dynamics underlying LVSI in CC remains elusive. Therefore, this study investigated tumor-immune microenvironment (TIME) dynamics of the LVSI-positive group in CC. RNA sequencing included formalin-fixed paraffin-embedded (FFPE) slides from 21 CC patients, and differentially expressed genes (DEGs) were analyzed. Functional analysis and immune deconvolution revealed aberrantly enriched PI3K/Akt pathway activation and a heterogenic immune composition with a low abundance of regulatory T cells (Treg) between LVSI-positive and LVSI-absent groups. These findings improve the comprehension of LSVI TIME and immune mechanisms, benefiting targeted LVSI therapy for CC.

Keywords

• cervical cancer
• lymphovascular space invasion
• RNA sequencing
• PI3K/Akt signaling pathway
• sustained angiogenesis
• immune deconvolution