Abstract
Purpose :
To develop a prognostic test based on serum samples obtained at diagnosis of uveal melanoma.
Methods :
Eighty-three patients diagnosed with primary melanoma in the choroid or ciliary body at St. Erik Eye Hospital, Stockholm, Sweden between 1996 and 2000. Serum samples from peripheral blood were obtained at diagnosis and kept at -80 °C until this analysis.
Proteome profiling of 84 different cancer-related proteins was used to screen for potential biomarkers. ELISA was then performed to evaluated serum levels of the best candidates. Receiver operating characteristics were used to define thresholds for metastatic risk. A prognostic test was developed (serUM) in a training cohort and tested in a validation cohort.
Results :
Of the 83 included patients, 43 (52 %) were female. Their mean age at diagnosis was 65 years (12.6 SD) their mean tumor diameter and thickness was 9.8 mm (3.7 SD) and 4.9 mm (2.3 SD). In proteome profiling, five proteins (Leptin, Osteopontin, Progranulin, Tenascin C and DLL-1) were included for further analysis. Receiver operating characteristics were used to define thresholds for metastatic risk. serUM, based on Leptin and Osteopontin concentrations, was developed in a training cohort (n=17) and then tested in a validation cohort (n=62) after exclusion of three patients with unreliable total protein fractions. Patients had gradually shorter cumulative metastasis-free survival with each increasing metastatic risk category (Log rank p for trend = 0.01). In multivariate Cox regression, serUM was an independent predictor of metastasis when entering all of tumor diameter, tumor thickness and patient age at diagnosis as covariates (hazard ratio 2.4, 95 % CI 1.0 to 5.3).
Conclusions :
serUM, a prognostic test based on serum obtained from a peripheral blood sample at diagnosis of uveal melanoma, is a strong predictor of metastasis. Future prospective studies should aim to validate these findings.
This abstract was presented at the 2022 ARVO Annual Meeting, held in Denver, CO, May 1-4, 2022, and virtually.