Department of Clinical Neuroscience, Division of Eye and Vision, Karolinska Institutet, 171 77 Stockholm, Sweden.
St. Erik Eye Hospital, 17164 Stockholm, Sweden.
Int J Mol Sci. 2024 Aug 9;25(16):8711. doi: 10.3390/ijms25168711.
Melatonin, noted for its anti-cancer properties in various malignancies, including cutaneous melanoma, shows promise in Uveal melanoma (UM) treatment. This study aimed to evaluate melatonin receptor expression in primary UM and its association with UM-related mortality and prognostic factors. Immunohistochemical analysis of 47 primary UM tissues showed low expression of melatonin receptor 1A (MTNR1A) and melatonin receptor 1B (MTNR1B), with MTNR1A significantly higher in patients who succumbed to UM. Analysis of TCGA data from 80 UM patients revealed RNA expression for MTNR1A, retinoic acid-related orphan receptor alpha (RORα), and N-ribosyldihydronicotinamide:quinone oxidoreductase (NQO2), but not MTNR1B or G protein-coupled receptor 50 (GPR50). Higher MTNR1A RNA levels were observed in patients with a BRCA1 Associated Protein 1 (BAP1) mutation, and higher NQO2 RNA levels were noted in patients with the epithelioid tumor cell type. However, Kaplan-Meier analysis did not show distinct survival probabilities based on receptor expression. This study concludes that UM clinical samples express melatonin receptors, suggesting a potential mechanism for melatonin's anti-cancer effects. Despite finding higher MTNR1A expression in patients who died of UM, no survival differences were observed.
褪黑素因其在各种恶性肿瘤中的抗癌特性而备受关注,包括皮肤黑色素瘤,在葡萄膜黑色素瘤(UM)治疗中显示出前景。本研究旨在评估褪黑素受体在原发性 UM 中的表达及其与 UM 相关死亡率和预后因素的关系。对 47 例原发性 UM 组织进行免疫组织化学分析显示,褪黑素受体 1A(MTNR1A)和褪黑素受体 1B(MTNR1B)表达水平较低,MTNR1A 在死于 UM 的患者中显著升高。对来自 80 例 UM 患者的 TCGA 数据进行分析显示,MTNR1A、视黄酸相关孤儿受体α(RORα)和 N-ribosyldihydronicotinamide:醌氧化还原酶(NQO2)的 RNA 表达,但 MTNR1B 或 G 蛋白偶联受体 50(GPR50)则不然。在 BRCA1 相关蛋白 1(BAP1)突变的患者中观察到更高的 MTNR1A RNA 水平,在具有上皮样肿瘤细胞类型的患者中观察到更高的 NQO2 RNA 水平。然而,Kaplan-Meier 分析并未根据受体表达显示出明显的生存概率差异。本研究得出结论,UM 临床样本表达褪黑素受体,提示褪黑素抗癌作用的潜在机制。尽管在死于 UM 的患者中发现了更高的 MTNR1A 表达,但未观察到生存差异。