A Cross-Sectional Exploratory Study of Rat Sarcoid (Ras) Activation in Women with and Without Polycystic Ovary Syndrome

Niinuma, Sara Anjum; Habib, Haniya; Takemoto, Ashleigh Suzu-Nishio; Das, Priya; Sathyapalan, Thozhukat; Atkin, Stephen L.; Butler, Alexandra E.

Abstract

Objective: Rat sarcoma (Ras) proteins, Kirsten, Harvey, and Neuroblastoma rat sarcoma viral oncogene homolog (KRAS, HRAS, and NRAS, respectively), are a family of GTPases, which are key regulators of cellular growth, differentiation, and apoptosis through signal transduction pathways modulated by growth factors that have been recognized to be dysregulated in PCOS. This study explores Ras signaling proteins and growth factor-related proteins in polycystic ovary syndrome (PCOS). Methods: In a well-validated PCOS database of 147 PCOS and 97 control women, plasma was batch analyzed using Somascan proteomic analysis for circulating KRas, Ras GTPase-activating protein-1 (RASA1), and 45 growth factor-related proteins. The cohort was subsequently stratified for BMI (body mass index), testosterone, and insulin resistance (HOMA-IR) for subset analysis. Results: Circulating KRas, and RASA1 did not differ between PCOS and control women (p > 0.05). EGF1, EGFR, and EGFRvIII were decreased in PCOS (p = 0.04, p = 0.04 and p < 0.001, respectively). FGF8, FGF9, and FGF17 were increased in PCOS (p = 0.02, p = 0.03 and p = 0.04, respectively), and FGFR1 was decreased in PCOS (p < 0.001). VEGF-D (p < 0.001), IGF1 (p < 0.001), IGF-1sR (p = 0.02), and PDGFRA (p < 0.001) were decreased in PCOS compared to controls. After stratifying for BMI ≤ 29.9 kg/m2, EGFR FGF8, FGFR1 VEGF-D, IGF1, and IGF-1sR differed (p < 0.05) though EGF1, EGFRvIII, FGF8, FGFR1, and VEGF-D no longer differed; after subsequently stratifying for HOMA-IR, only FGFR1, VEGF-D, IGF1, and IGF-1sR differed between groups (p < 0.05). Conclusions: Several growth factors that activate Ras differ between women with and without PCOS, and when stratified for BMI and HOMA-IR, only FGFR1, VEGF-D, IGF1, and IGF-1sR differed; these appear to be inherent features of the pathophysiology of PCOS.

Citation

Niinuma, S. A., Habib, H., Takemoto, A. S.-N., Das, P., Sathyapalan, T., Atkin, S. L., & Butler, A. E. (2025). A Cross-Sectional Exploratory Study of Rat Sarcoid (Ras) Activation in Women with and Without Polycystic Ovary Syndrome. Cells, 14(5), Article 377. https://doi.org/10.3390/cells14050377

• Journal Article Type: Article
• Acceptance Date: Mar 4, 2025
• Online Publication Date: Mar 5, 2025
• Publication Date: Mar 1, 2025
• Deposit Date: Mar 12, 2025
• Publicly Available Date: Mar 14, 2025
• Journal: Cells
• Electronic ISSN: 2073-4409
• Publisher: MDPI
• Peer Reviewed: Peer Reviewed
• Volume: 14
• Issue: 5
• Article Number: 377
• DOI: https://doi.org/10.3390/cells14050377
• Keywords: Polycystic ovary syndrome (PCOS); Cardiovascular risk; Biomarkers; Proteomics; Rat sarcoid proteins; Ras
• Public URL: https://hull-repository.worktribe.com/output/5078161