Assessing the Metabolic\nVariations of Invasive and\nNoninvasive Unilateral Retinoblastoma Patients

Retinoblastoma (Rb) is a pediatric eye cancer which if\ndiagnosed\nat later stages can lead to Rb invasion into the choroid, optic nerve,\nsclera, or beyond, with the potential of undergoing metastasis. Cancer\ncells, including Rb cells, reprogram their metabolic circuits for\ntheir own survival and progression, which provides a great opportunity\nto monitor the extent of Rb progression based on metabolic differences.\nHenceforth, the present study aims to map the metabolic variations\nin patients with invasive (primarily enucleated eyes with high-risk\nhistopathological features) and noninvasive (eyes salvaged with treatment)\nunilateral retinoblastoma (Rb) using nuclear magnetic resonance (NMR)\n based serum metabolomics. Quantification of differential metabolites\nin the serum obtained from 9 patients with invasive and 4 with noninvasive\nunilateral Rb along with 6 controls (no retinal pathology) was carried\nout using <sup>1</sup>H NMR spectroscopy. A total of 71 metabolites,\nsuch as organic acids, amino acids, carbohydrates, and others, were\nidentified in the serum obtained from 9 patients with invasive and\n4 with noninvasive unilateral Rb. Partial least-squares discriminant\nanalysis (PLS-DA) models depicted distinct grouping of invasive and\nnoninvasive Rb patients and controls. Differential metabolic fingerprints\nwere observed for invasive and noninvasive Rb patients based on their\nbiostatistical analyses with respect to controls. Remarkable perturbation\nwas observed among various metabolites such as 4-aminobutyrate, 2-phosphoglycerate, <i>O</i>-phosphocholine, proline, Sn-glycero-3-phosphocholine (Sn-GPC),\nand <i>O</i>-phosphoethanolamine in noninvasive and invasive\nRb patients with most of the effects being heightened in the latter\ngroup. Metabolic changes unique to invasive and noninvasive Rb patients\nwere also observed. Multivariate receiver operating characteristics\n(ROC) analysis unveiled the highest accuracy and potency of ROC models\n2 and 5 to distinguish the noninvasive and invasive Rb from controls,\nrespectively. Metabolites identified in the serum of patients with\ninvasive and noninvasive Rb may aid in advancing our knowledge about\nRb tumor biology. Differential aberrant metabolic variations in patients\nwith invasive Rb compared to those with noninvasive Rb may guide the\ndecision of enucleation versus globe salvage.