Plasminogen activator inhibitor 1 is associated with high-grade serous ovarian cancer metastasis and is reduced in patients who have received neoadjuvant chemotherapy

• DOI: 10.3389/fcell.2023.1150991
• Publication Date: 2023-12-07T14:44:36Z
• Authors: Tanya E. Kelly; Cathy L. Spillane; Mark P. Ward; Karsten Hokamp; Yanmei Huang; Prerna Tewari; Cara M. Martin; Lucy A. Norris; Bashir M. Mohamed; Mark Bates; Robert Brooks; Stavros Selemidis; Douglas A. Brooks; Waseem Kamran; Feras Abu Saadeh; Sharon A. O’Toole; John J. O’Leary
• Keywords: Plasminogen activator inhibitor-1; Circulating tumor cell; Serpin

Introduction: High-grade serous ovarian cancer (HGSOC) is the most prevalent and deadliest subtype of epithelial (EOC), killing over 140,000 people annually. Morbidity mortality are compounded by a lack screening methods, recurrence common. Plasminogen-activator-inhibitor 1 (PAI-1, protein product SERPIN E1) involved in hemostasis, extracellular matrix (ECM) remodeling, tumor cell migration invasion. Overexpression associated with poor prognosis EOC. Platelets significantly increase PAI-1 cells vitro, may contribute to hematogenous metastasis circulating (CTCs). CTCs viable that intravasate travel through circulation-often aided platelets - potential form secondary metastases. Here, we provide evidence central platelet-cancer interactome, plays role metastatic cascade. Methods: SK-OV-3 where had been silenced, treated healthy donor platelets, platelet-conditioned medium were used as an vitro model Gene expression analysis was performed using RNA-Seq data from untreated siRNA or negative control, each without platelets. Four cohorts banked patient plasma samples (n = 239) assayed for ELISA. Treatment-naïve (TN) whole blood (WB) evaluated conjunction evaluation matched plasma. Results discussion: Significant phenotypic changes occurring when silenced added reflected RNA-seq data, observed be molecular mechanisms EOC metastasis. Increased proliferation Plasma correlated advanced disease TN cohort, reduced neoadjuvant chemotherapy (NACT) cohort. demonstrated trend towards significance overall survival (OS) late-stage correlation between neutrophils this cohort significant. 72.7% (16/22) patients levels higher than OS cutoff CTC-positive. These support metastasis, highlight PAI-1's biomarker, prognostic indicator, gauge treatment response HGSOC.