Malignant Transformed and Non-Transformed Oral Leukoplakias Are Metabolically Different

Understanding the early molecular events driving oral carcinogenesis is vital for diagnosing oral squamous cell carcinoma (OSCC) promptly. While metabolic differences between oral leukoplakia (OLK), OSCC, and healthy oral mucosa have been reported, the metabolic changes distinguishing malignant transformed OLKs (MT-OLK) from non-transformed OLKs (NT-OLK) remain unexplored. Here, we examine the metabolomic profiles of 5 cases of MT-OLK and 15 of NT-OLK to identify key predictive molecules using untargeted high-performance liquid chromatography-mass spectrometry. The potentially discriminant compounds were highlighted through a robust statistical analysis workflow, and the dysregulated metabolic pathways were illustrated by enrichment analysis. Seventeen molecular features, primarily lipids-including phospholipids, oxidised lipids, cholesteryl esters, and fatty acids-were identified as discriminants between MT-OLK and NT-OLK across statistical and bioinformatic approaches. Pathway enrichment analysis revealed alterations in lipid metabolism, particularly fatty acid synthesis and degradation, steroid hormone biosynthesis, and glycerophospholipid metabolism. Predictive models showed high accuracy (AUC = 0.88) in distinguishing the two groups. This study suggests that metabolomics has the potential to differentiate between MT-OLK and NT-OLK by identifying candidate biomarkers that may contribute to the understanding of malignant transformation. Validation in larger cohorts is warranted to translate these findings into clinical practice.

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Publication Details

Journal
International Journal of Molecular Sciences
Published
2025-02-20
DOI
https://doi.org/10.3390/ijms26051802
Citations
1
Primary Topic
Oral Health Pathology and Treatment
Type
article
Field-Weighted Citation Impact
1.47

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article

Malignant Transformed and Non-Transformed Oral Leukoplakias Are Metabolically Different

Jéssica Gardone Vitório, Filipe Fideles Duarte‐Andrade, Liséte Celina Lange, Yuri Abner Rocha Lebron et al.
1 citations
International Journal of Molecular Sciences
Oral Health Pathology and Treatment
1.47
article

Malignant Transformed and Non-Transformed Oral Leukoplakias Are Metabolically Different

Jéssica Gardone Vitório, Filipe Fideles Duarte‐Andrade, Liséte Celina Lange, Yuri Abner Rocha Lebron, Victor Coutinho Bastos, Monique Sedlmaier França, Roberta Rayra Martins‐Chaves, Adriana Nori de Macedo, Thaís dos Santos Fontes Pereira, Ricardo Santiago Gomez, Gisele André Baptista Canuto, Marina Gonçalves Diniz, Victor Rezende Moreira, Carolina Raíssa Costa Picossi, Lucilaine Valéria de Souza Santos, Hélder Antônio Rebelo Pontes, Flávia Leite‐Lima, Carolina Cavaliéri Gomes, Wagner Henriques Castro, Thaís Ellen Chaves Gomes
article en
1 citations

Abstract

Understanding the early molecular events driving oral carcinogenesis is vital for diagnosing oral squamous cell carcinoma (OSCC) promptly. While metabolic differences between oral leukoplakia (OLK), OSCC, and healthy oral mucosa have been reported, the metabolic changes distinguishing malignant transformed OLKs (MT-OLK) from non-transformed OLKs (NT-OLK) remain unexplored. Here, we examine the metabolomic profiles of 5 cases of MT-OLK and 15 of NT-OLK to identify key predictive molecules using untargeted high-performance liquid chromatography-mass spectrometry. The potentially discriminant compounds were highlighted through a robust statistical analysis workflow, and the dysregulated metabolic pathways were illustrated by enrichment analysis. Seventeen molecular features, primarily lipids-including phospholipids, oxidised lipids, cholesteryl esters, and fatty acids-were identified as discriminants between MT-OLK and NT-OLK across statistical and bioinformatic approaches. Pathway enrichment analysis revealed alterations in lipid metabolism, particularly fatty acid synthesis and degradation, steroid hormone biosynthesis, and glycerophospholipid metabolism. Predictive models showed high accuracy (AUC = 0.88) in distinguishing the two groups. This study suggests that metabolomics has the potential to differentiate between MT-OLK and NT-OLK by identifying candidate biomarkers that may contribute to the understanding of malignant transformation. Validation in larger cohorts is warranted to translate these findings into clinical practice.

International Journal of Molecular SciencesVol. 26(5)
Universidade Federal de Minas Gerais (BR), Universidade Federal da Bahia (BR), Universidade de São Paulo (BR), Faculdade de Ciências Médicas de Minas Gerais (BR), Universidade Federal do Pará (BR)
Chalmers Tekniska Högskola
Openalex Percentile: Top 22%
Oral Health Pathology and Treatment
1.47
DOIOpen Access PDFOpenAlex
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