Gulati Khushboo, Poluri Krishna Mohan, Kaliki Swathi
The Operation Eyesight Universal Institute for Eye Cancer, L. V. Prasad Eye Institute, Hyderabad 500034, Telangana, India.
Brien Holden Eye Research Center, L. V. Prasad Eye Institute, Hyderabad 500034, Telangana, India.
ACS Omega. 2024 Sep 12;9(38):40082-40094. doi: 10.1021/acsomega.4c06014. eCollection 2024 Sep 24.
Retinoblastoma (Rb) is a pediatric eye cancer which if diagnosed at later stages can lead to Rb invasion into the choroid, optic nerve, sclera, or beyond, with the potential of undergoing metastasis. Cancer cells, including Rb cells, reprogram their metabolic circuits for their own survival and progression, which provides a great opportunity to monitor the extent of Rb progression based on metabolic differences. Henceforth, the present study aims to map the metabolic variations in patients with invasive (primarily enucleated eyes with high-risk histopathological features) and noninvasive (eyes salvaged with treatment) unilateral retinoblastoma (Rb) using nuclear magnetic resonance (NMR) based serum metabolomics. Quantification of differential metabolites in the serum obtained from 9 patients with invasive and 4 with noninvasive unilateral Rb along with 6 controls (no retinal pathology) was carried out using H NMR spectroscopy. A total of 71 metabolites, such as organic acids, amino acids, carbohydrates, and others, were identified in the serum obtained from 9 patients with invasive and 4 with noninvasive unilateral Rb. Partial least-squares discriminant analysis (PLS-DA) models depicted distinct grouping of invasive and noninvasive Rb patients and controls. Differential metabolic fingerprints were observed for invasive and noninvasive Rb patients based on their biostatistical analyses with respect to controls. Remarkable perturbation was observed among various metabolites such as 4-aminobutyrate, 2-phosphoglycerate, -phosphocholine, proline, Sn-glycero-3-phosphocholine (Sn-GPC), and -phosphoethanolamine in noninvasive and invasive Rb patients with most of the effects being heightened in the latter group. Metabolic changes unique to invasive and noninvasive Rb patients were also observed. Multivariate receiver operating characteristics (ROC) analysis unveiled the highest accuracy and potency of ROC models 2 and 5 to distinguish the noninvasive and invasive Rb from controls, respectively. Metabolites identified in the serum of patients with invasive and noninvasive Rb may aid in advancing our knowledge about Rb tumor biology. Differential aberrant metabolic variations in patients with invasive Rb compared to those with noninvasive Rb may guide the decision of enucleation versus globe salvage.
视网膜母细胞瘤（Rb）是一种儿童眼部癌症，如果在晚期被诊断出来，可能会导致Rb侵犯脉络膜、视神经、巩膜或其他部位，并有可能发生转移。癌细胞，包括Rb细胞，会重新编程其代谢途径以实现自身的存活和进展，这为基于代谢差异监测Rb进展程度提供了一个绝佳机会。因此，本研究旨在利用基于核磁共振（NMR）的血清代谢组学方法，描绘侵袭性（主要是具有高危组织病理学特征的眼球摘除术）和非侵袭性（经治疗挽救的眼球）单侧视网膜母细胞瘤（Rb）患者的代谢变化。使用1H NMR光谱对9例侵袭性和4例非侵袭性单侧Rb患者以及6例对照（无视网膜病变）的血清中的差异代谢物进行定量分析。在9例侵袭性和4例非侵袭性单侧Rb患者的血清中总共鉴定出71种代谢物，如有机酸、氨基酸、碳水化合物等。偏最小二乘判别分析（PLS-DA）模型显示侵袭性和非侵袭性Rb患者及对照有明显分组。基于与对照的生物统计学分析，观察到侵袭性和非侵袭性Rb患者的差异代谢指纹。在非侵袭性和侵袭性Rb患者中，4-氨基丁酸、2-磷酸甘油酸、磷酸胆碱、脯氨酸、Sn-甘油-3-磷酸胆碱（Sn-GPC）和磷酸乙醇胺等多种代谢物出现了显著扰动，其中大多数影响在后者组中更为明显。还观察到侵袭性和非侵袭性Rb患者独特的代谢变化。多变量受试者工作特征（ROC）分析表明，ROC模型2和5分别区分非侵袭性和侵袭性Rb与对照的准确性和效能最高。在侵袭性和非侵袭性Rb患者血清中鉴定出的代谢物可能有助于增进我们对Rb肿瘤生物学的了解。与非侵袭性Rb患者相比，侵袭性Rb患者不同的异常代谢变化可能指导眼球摘除术与眼球挽救的决策。
