Department of Ophthalmology, Erasmus MC, 3000 CA Rotterdam, The Netherlands.
Department of Clinical Genetics, Erasmus MC, 3000 CA Rotterdam, The Netherlands.
Int J Mol Sci. 2023 Mar 7;24(6):5077. doi: 10.3390/ijms24065077.
Uveal melanomas (UM) are detected earlier. Consequently, tumors are smaller, allowing for novel eye-preserving treatments. This reduces tumor tissue available for genomic profiling. Additionally, these small tumors can be hard to differentiate from nevi, creating the need for minimally invasive detection and prognostication. Metabolites show promise as minimally invasive detection by resembling the biological phenotype. In this pilot study, we determined metabolite patterns in the peripheral blood of UM patients (n = 113) and controls (n = 46) using untargeted metabolomics. Using a random forest classifier (RFC) and leave-one-out cross-validation, we confirmed discriminatory metabolite patterns in UM patients compared to controls with an area under the curve of the receiver operating characteristic of 0.99 in both positive and negative ion modes. The RFC and leave-one-out cross-validation did not reveal discriminatory metabolite patterns in high-risk versus low-risk of metastasizing in UM patients. Ten-time repeated analyses of the RFC and LOOCV using 50% randomly distributed samples showed similar results for UM patients versus controls and prognostic groups. Pathway analysis using annotated metabolites indicated dysregulation of several processes associated with malignancies. Consequently, minimally invasive metabolomics could potentially allow for screening as it distinguishes metabolite patterns that are putatively associated with oncogenic processes in the peripheral blood plasma of UM patients from controls at the time of diagnosis.
葡萄膜黑色素瘤 (UM) 被更早地发现。因此，肿瘤更小，允许采用新的保眼治疗方法。这减少了可用于基因组分析的肿瘤组织。此外，这些小肿瘤可能难以与痣区分，这就需要进行微创检测和预后判断。代谢物作为微创检测具有潜力，因为它们类似于生物表型。在这项初步研究中，我们使用非靶向代谢组学检测了 UM 患者（n=113）和对照组（n=46）的外周血中的代谢物模式。使用随机森林分类器（RFC）和留一法交叉验证，我们证实了 UM 患者与对照组之间存在有区别的代谢物模式，正离子和负离子模式的曲线下面积（ROC）均为 0.99。RFC 和留一法交叉验证未显示出 UM 患者高转移风险与低转移风险之间存在有区别的代谢物模式。使用 50%随机分布样本重复 10 次分析 RFC 和 LOOCV，对 UM 患者与对照组和预后组的结果相似。使用注释代谢物进行的途径分析表明，与恶性肿瘤相关的几个过程失调。因此，微创代谢组学可能具有筛查潜力，因为它可以区分 UM 患者外周血血浆中与致瘤过程相关的代谢物模式，与对照组在诊断时区分开来。
