Obesity paradox in uveal melanoma: High body mass index is associated with low metastatic risk

Abstract

Background Metabolic factors and obesity may influence the development and progression of cancer. In this study, we examine their association with the risk of developing metastases of uveal melanoma. Methods Data on metabolic factors, medications, serum leptin levels, tumour leptin receptor RNA expression and clinical outcomes were examined in three cohorts. HRs for metastasis and cumulative incidences of melanoma-related mortality were calculated, and the levels of tumour leptin receptor expression were compared with prognostic factors including BAP1 mutation, and tumour cell morphology. Results Of 581 patients in the main cohort, 116 (20%) were obese and 7 (1 %) had metastatic disease at presentation. In univariate Cox regressions, tumour diameter, diabetes type II and use of insulin were associated with metastases, but patients with obesity had a lower risk. The beneficial prognostic implication of obesity was retained in multivariate regressions. In competing risk analyses, the incidence of melanoma-related mortality was significantly lower for patients with obesity. Serum leptin levels≥median were associated with a reduced risk for metastasis, independent of patient sex and cancer stage in a separate cohort (n=80). Similarly, in a third cohort (n=80), tumours with BAP1 mutation and epithelioid cells had higher leptin receptor RNA expression levels, which have a negative correlation with serum leptin levels. Conclusion Obesity and elevated serum leptin levels are associated with a lower risk for developing metastases and dying from uveal melanoma.