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

• Published in: Life (Basel, Switzerland) Vol. 13; no. 12; p. 2342
• Main Authors: Choi, Yeseul, Ando, Yu, Lee, Donghyeon, Kim, Na Young, Lee, Olive E M, Cho, Junghwan, Seo, Incheol, Chong, Gun Oh, Park, Nora Jee-Young
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 14-12-2023
• Subjects: 1-Phosphatidylinositol 3-kinase; AKT protein; Cancer; Cancer therapies; Cervical cancer; Chemotherapy; Clinical significance; Cytokines; Fibroblasts; Functional analysis; Gene sequencing; Genes; immune deconvolution; Immunoregulation; Lymph nodes; Lymphatic system; Lymphocytes; Lymphocytes T; lymphovascular space invasion; Medical prognosis; Metastases; Metastasis; Microenvironments; Molecular modelling; Patients; PI3K/Akt signaling pathway; RNA sequencing; Signal transduction; Survival; sustained angiogenesis; Tumors; United States > US; RNA sequencing; immune deconvolution; regulatory T cells; sustained angiogenesis; lymphovascular space invasion; tumor immune microenvironment; TIME; PI3K/Akt signaling pathway; cervical cancer
• ISSN: 2075-1729; 2075-1729
• DOI: 10.3390/life13122342

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.