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. 2020 Sep:198:108140.
doi: 10.1016/j.exer.2020.108140. Epub 2020 Jul 7.

Metabolic signature of eyelid basal cell carcinoma

Jiancheng Huang  1 , Jamie Schaefer  2 , Yekai Wang  3 , Lauren Gioia  2 , Ying Pei  4 , Xiaofei Shi  4 , Shanawar Waris  2 , Chen Zhao  5 , John Nguyen  6 , Jianhai Du  7
Affiliations

Metabolic signature of eyelid basal cell carcinoma

Jiancheng Huang et al. Exp Eye Res. 2020 Sep.

Abstract

Eyelid basal cell carcinoma (BCC) is the most common eyelid malignancy. Metabolic reprogramming is critical in tumorigenesis, but the metabolic feature of eyelid BCC remains elusive. In this study, we aim to reveal the metabolic profile in eyelid BCC using targeted metabolomics. Eyelid samples were collected from patients who had removal of BCC and from control patients who underwent blepharoplasty. Multivariate analysis of metabolomics data distinguished the two groups, indicating that eyelid BCC has significantly different metabolome than the healthy tissue. We found 16 increased and 11 decreased metabolites in the BCC tissues. These metabolites were highly enriched in the metabolism of nicotinamide adenine dinucleotide (NAD), glutathione metabolism, polyamine metabolism, and the metabolism of glycine, serine, threonine, arginine and proline. amino acid metabolism. Metabolites from NAD metabolism (Nicotinamide; Nicotinamide riboside; N1-Methylnicotinamide) had the highest sensitivity, specificity, and prediction accuracy in a prediction model for eyelid BCC. In conclusion, eyelid BCC has a signature change of cell metabolome. Metabolites in NAD metabolic pathways could potentially be biomarkers or therapeutic targets for eyelid BCC.

Keywords: Eyelid basal cell carcinoma; LC-MS/MS; Metabolism.

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Figures

Figure 1:
Figure 1:. Overview of changed metabolites
(A) The PLS-DA score plot clearly discriminates BCC from normal subjects. (B) VIP score (VIP > 1.1) derived from PLS-DA model is shown. (C) Volcano plot and column graph (Fold change > 2.0, P< 0.05) of changed metabolites is shown. (D) Heat map of top 25 changed metabolites. NAM: nicotinamide; N1-MNAM: N1-Methylnicotinamide; 3-HD: 3-Hydroxykynurenine; Dihydrosphingosine: DHS; PC: Propionyl Carnitine; PA: Pyroglutamic Acid; 3-HB: 3-Hydroxybutyrate; 2-MC: 2 Methylbutyryl Carnitine;
Figure 2:
Figure 2:
Pathway analysis of changed metabolites
Figure 3:
Figure 3:. Univariate and multivariate analysis of metabolites from NAD metabolic pathway
The change of metabolites from NAD metabolic pathway (* P< 0.05) (NAD (A); NR (B); NAM (C); N1-MNAM (D)).
Figure 4:
Figure 4:. Multivariate analysis of NAD metabolic pathway
ROC curve of metabolites from NAD metabolic pathway (NAM (A); NR (B); NAD (C); N1-MNAM (D)). (E) ROC curve of NAD metabolic pathway (NAM; NR; NAD; N1-MNAM) in BCC and normal subjects after PLS-DA analysis Using targeted metabolomics, we reveal metabolic features in the most common eyelid malignancy, basal cell carcinoma (BCC). Eyelid BCC alters NAD metabolism, glutathione metabolism, polyamine metabolism, and amino acid metabolism. Metabolites in NAD pathways are potential biomarkers and therapeutic targets for eyelid BCC.
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