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. Data are available upon reasonable request. The results published here are in part based upon data generated by the TCGA Research Network: .

中文翻译：

---

葡萄膜黑色素瘤的肥胖悖论：高体重指数与低转移风险相关

背景代谢因素和肥胖可能影响癌症的发生和进展。在这项研究中，我们检查了它们与葡萄膜黑色素瘤发生转移的风险之间的关系。方法 在三个队列中检查代谢因素、药物、血清瘦素水平、肿瘤瘦素受体 RNA 表达和临床结果的数据。计算转移的 HR 和黑色素瘤相关死亡率的累积发生率，并将肿瘤瘦素受体表达水平与 BAP1 突变和肿瘤细胞形态等预后因素进行比较。结果 在主要队列的 581 名患者中，116 名 (20%) 患有肥胖症，7 名 (1%) 就诊时患有转移性疾病。在单变量 Cox 回归中，肿瘤直径、II 型糖尿病和胰岛素的使用与转移相关，但肥胖患者的风险较低。肥胖的有益预后意义保留在多变量回归中。在竞争性风险分析中，肥胖患者的黑色素瘤相关死亡率显着较低。在单独的队列中，血清瘦素水平≥中位数与转移风险降低相关，与患者性别和癌症分期无关（n=80）。同样，在第三组（n=80）中，具有 BAP1 突变的肿瘤和上皮样细胞具有较高的瘦素受体 RNA 表达水平，这与血清瘦素水平呈负相关。结论 肥胖和血清瘦素水平升高与葡萄膜黑色素瘤发生转移和死亡的风险较低相关。数据可根据合理要求提供。这里发布的结果部分基于 TCGA 研究网络生成的数据：。