Increased IGF2 and Immunosuppressive Cell Populations in Ascites of Patients with Recurrent High-Grade Serous Ovarian...

Background/Objectives: Ovarian cancer is frequently diagnosed at advanced stages, during which ascites serves as a microenvironment conducive to cancer recurrence. This study aimed to identify factors in ascites specimens that could be targeted for the detection and prevention of recurrence of the most common and lethal histology type, high-grade serous ovarian cancer (HGSOC). Methods: Ascites specimens were collected from patients with HGSOC who provided informed consent. RNA was isolated from ascites cells, sequenced, and compared between ascites cells in two initial and four recurrent HGSOC samples using DRAGENv.4.2.4 to identify differentially expressed genes. Immune cell populations were estimated from the differentially expressed genes using deconvolution analysis. ELISA and antibody isotyping were used to evaluate cell-free ascitic fluid (N = 24) and banked serum (N = 23) collected from independent groups of patients with HGSOC who provided informed consent. Results: Transcriptomics analysis identified reduced expression of immunoglobulin variable chains in the recurrent ascites group. The primary immunoglobulin present in all ascites specimens was IgG1, whereas IgG2 and IgG3 appeared to be present at higher levels in recurrent ascites. Deconvolution analysis estimated a more suppressive immune cell population profile in the recurrent samples. The immunosuppressor insulin-like growth factor 2 (IGF2) was the most differentially expressed gene, with higher expression in recurrent ascites than in initial ascites. Significantly higher levels of IGF2 protein were measured in recurrent cell-free ascites fluid than in initial cell-free ascites fluid. Conclusions: In conclusion, IGF2 and suppressive immune cell populations were identified as candidate drug targets for prevention of ovarian cancer recurrence.