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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.

Authors

Sara Anjum Niinuma

Haniya Habib

Ashleigh Suzu-Nishio Takemoto

Priya Das

Stephen L. Atkin

Alexandra E. Butler



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

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Publisher Licence URL
http://creativecommons.org/licenses/by/4.0

Copyright Statement
© 2025 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).




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