Identification of Possible Salivary Metabolic Biomarkers and Altered Metabolic Pathways in South American Patients Diagnosed with Oral Squamous Cell Carcinoma.

Mariana De Sá Alves,Janete Dias Almeida,Meriellen Dias,Nayara De Sá Rodrigues,Celso Muller Bandeira,Maria Anita Mendes,Maria Beatriz Nogueira Pascoal,Gabrielle Luana Jimenez Teodoro Nepomuceno,José Francisco Sales Chagas,Herculano Da Silva Martinho,Mônica Ghislaine Oliveira Alves,Levy Anderson César Alves

doi:10.3390/metabo11100650

Abstract

Oral squamous cell carcinoma (OSCC) represents 90% of oral malignant neoplasms. The search for specific biomarkers for OSCC is a very active field of research contributing to establishing early diagnostic methods and unraveling underlying pathogenic mechanisms. In this work we investigated the salivary metabolites and the metabolic pathways of OSCC aiming find possible biomarkers. Salivary metabolites samples from 27 OSCC patients and 41 control individuals were compared through a gas chromatography coupled to a mass spectrometer (GC-MS) technique. Our results allowed identification of pathways of the malate-aspartate shuttle, the beta-alanine metabolism, and the Warburg effect. The possible salivary biomarkers were identified using the area under receiver-operating curve (AUC) criterion. Twenty-four metabolites were identified with AUC > 0.8. Using the threshold of AUC = 0.9 we find malic acid, maltose, protocatechuic acid, lactose, 2-ketoadipic, and catechol metabolites expressed. We notice that this is the first report of salivary metabolome in South American oral cancer patients, to the best of our knowledge. Our findings regarding these metabolic changes are important in discovering salivary biomarkers of OSCC patients. However, additional work needs to be performed considering larger populations to validate our results.

Highlights

Oral cancer refers to the set of malignant neoplasms that affect the lips and other intraoral regions [1]
The relevance of the investigation of the salivary metabolome of oral malignancies squamous cell carcinoma (OSCC) relies on the identification of predominantly altered metabolic pathways which may lead to the discovery of possible biomarkers
Our findings indicate that the Warburg effect was one of the metabolic pathways activated in OSCC patients

Summary

Introduction

Oral cancer refers to the set of malignant neoplasms that affect the lips and other intraoral regions [1] It represents the 16th most common neoplasm in the world, with 355,000 new diagnoses and 177,000 deaths in 2018 [2]. OSCC has a survival rate of approximately 80% for individuals detected with early stage disease (stage I) when compared to a rate of 20–30% in patients diagnosed at advanced stages (stages III–IV) [7]. This fact emphasizes the importance of early diagnosis. About 50% of cases are diagnosed in advanced stages (III and IV) [8,9] which implies a worse prognosis, increased costs, and a high mortality rate [10,11]

Methods

Discussion

Conclusion