Profiling of Lymphovascular Space Invasion in Cervical Cancer Revealed PI3K/Akt Signaling Pathway Overactivation and Heterogenic Tumor-Immune Microenvironments.
Yeseul ChoiYu AndoDonghyeon LeeNa Young KimOlive E M LeeJunghwan Joshua ChoIncheol SeoGun Oh ChongNora Jee-Young ParkPublished in: Life (Basel, Switzerland) (2023)
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.
Keyphrases
- lymph node metastasis
- pi k akt
- signaling pathway
- poor prognosis
- regulatory t cells
- single cell
- squamous cell carcinoma
- long non coding rna
- cell proliferation
- stem cells
- end stage renal disease
- newly diagnosed
- ejection fraction
- chronic kidney disease
- cell migration
- gene expression
- dna methylation
- oxidative stress
- lymph node
- epithelial mesenchymal transition
- cancer therapy
- prognostic factors
- high resolution
- patient reported outcomes
- single molecule