Abstract
Purpose: It is very important to develop potential molecular associated with oral squamous cell carcinoma (OSCC) malignant transformation and progression. Thus, the aim of our study was to determine the amino acid metabolic characteristics of OSCC patients and test their diagnostic value.Experimental Design: Eight pairs of matched tumor and normal samples were collected for gas chromatography–mass spectrometry (GC-MS) high-throughput untargeted analysis. Another 20 cases (each case including tumor and normal tissues) were also enrolled for ultrahigh-performance liquid chromatography–tandem mass spectrometer (UHPLC-MS/MS) amino acid quantitative analysis. T-test and receiver operating characteristic (ROC) curve analysis were used to determine candidate markers. Principal component analysis, partial least squares discriminant analysis, and heat map analysis were used to verify the ability of candidate markers to distinguish tumors from normal tissues.Results: A total of 10 amino acids biomarker were selected as OSCC candidate diagnostic biomarkers by GC-MS high-throughput untargeted metabolomics analyses [area under the curve (AUC) >0.80]. We further measured the specific concentration of these candidate amino acids biomarkers in another batch of 20 cases by UHPLC-MS/MS quantitative analysis. The result validated that nine amino acids had been detected, which had statistically significant difference (t-test, p < 0.05). Moreover, three of nine amino acid markers (glutamate, aspartic acid, and proline) displayed high sensitivity and specificity (AUC >0.90) by ROC curve analysis and obtained optimal sensitivity and specificity by binary logistic regression in the Glmnet package (AUC = 0.942).Conclusions: In conclusion, a panel including three amino acids (glutamate, aspartic acid, and proline) was identified as potential diagnostic biomarkers of OSCC by a combination of non-targeted and targeted metabolomics methods.
Highlights
Oral squamous cell carcinoma (OSCC) is one of the most common malignant tumors in the head and neck region
A total of 28 cases were included in the study, eight cases of which were used for gas chromatography–mass spectrometry (GC-MS) highthroughput untargeted analysis, and another 20 cases were used for UHPLC-MS amino acid targeted quantitative analysis
A total of 10 amino acids were selected as OSCC candidate diagnostic biomarkers by GC-MS untargeted metabolomics analyses
Summary
Oral squamous cell carcinoma (OSCC) is one of the most common malignant tumors in the head and neck region. It is very important to study the metabolic mechanism of oral cancer progression, which will help improve the diagnosis and treatment of oral cancer. Many studies have confirmed that OSCC tissues undergo significant metabolic changes compared to normal tissues, such as lactate, glycine, proline, and hydroxyproline, 3AMP, uracil, spermidine, and c-glycosyltryptophan, 2-hydroxyglutarate, and glycerol-3monophosphate high expression in tumor tissues [21, 27]. The metabolic pathways associated with oral cancer mainly include glycolysis, amino acid metabolism and pentose phosphate pathway, and RNA biosynthesis. Cancer cells can get energy from other metabolic pathways, such as amino acid and lipid metabolism [7,8,9]
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