Introduction: This study evaluated the association between gene expression profiling (GEP), PRAME (preferentially expressed antigen in melanoma), and regression rate of uveal melanoma after proton beam irradiation (PBI). Methods: A retrospective review of uveal melanoma patients treated with PBI between 2013 and 2021, with GEP results and at least 3 post-radiation ultrasound measurements, was conducted. Patients with local recurrences were excluded. Regression rates were analyzed using a linear mixed model to predict percentage change in thickness from baseline. Cox regression was conducted to determine whether slow or fast regression, based on the median regression rate at 18 months, correlates with metastasis risk. Results: The study included 106 patients, with GEP classifications of 1A in 43.4%, 1B in 25.5%, and 2 in 31.1%. Overall, the mean change in tumor thickness was 20.9%, 35.1%, 51.4%, and 59.3% at 1 year, 2 years, 4 years, and 6 years, respectively. No differences in regression rates between GEP classes and PRAME expression were found through 72 months post-PBI. The median regression at 18 months was 27.1%. Slow and fast regression was not associated with the risk of metastasis. Conclusion: No association between GEP, PRAME, and regression rate was found through 72 months post-PBI.

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