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bioRxiv · 10.1101/2025.02.05.636637

Profiling serum oxylipin metabolites across melanoma subtypes and immunotherapy responders

Goodman, A. C.·Michel, K. M.·MacBeth, M. L.·Turner, J. A.·Tobin, R. P.·Robinson, W. A.·Couts, K. L.
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Abstract

ObjectivesThis study investigates the relationship between serum oxylipin profiles and response to immune checkpoint inhibitor therapy in melanoma subtypes to identify potential metabolic biomarkers for treatment response. MethodsIn a retrospective cohort study, serum samples from 43 stage III and stage IV melanoma patients treated at the University of Colorado Hospital from 2010 to 2023 were analyzed via ultra-high-pressure liquid chromatography-mass spectrometry. Melanoma patients were treated anti-PD-1 monotherapy or combination immune checkpoint inhibitor therapy and response was assessed using RECIST 1.1 criteria. ResultsUsing mass spectroscopy, we determined global oxylipin metabolite profiles are largely uniform pre-and post-treatment across melanoma subtypes including cutaneous, acral, mucosal, and uveal melanoma. Across subtypes, 33 oxylipin metabolites were analyzed, with limited variation observed overall. Prostaglandin J2 was more abundant in rare melanoma subtypes including acral, mucosal, and uveal melanoma compared to cutaneous melanoma. ConclusionsDespite limited variation of serum oxylipin molecular species by subtype and response status, we observed significant differences in Prostaglandin J2 which could serve as a potential biomarker for immune checkpoint inhibitor therapy response in melanoma. However, further investigation is warranted to explore the role of oxylipins in immune response modulation.

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Goodman, A. C., Michel, K. M., MacBeth, M. L., Turner, J. A., Tobin, R. P., Robinson, W. A., Couts, K. L.. 2025-02-06. Profiling serum oxylipin metabolites across melanoma subtypes and immunotherapy responders. https://doi.org/10.1101/2025.02.05.636637

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