The early diagnosis and monitoring of squamous cell carcinoma via saliva metabolomics

Abstract

Early diagnosis of oral squamous cell carcinoma (OSCC) is an attractive strategy to increase survival rate of patient. An integrated separation approach of reversed phase liquid chromatography and hydrophilic interaction chromatography combining with time of flight mass spectrometer has been firstly developed for performing global saliva metabonomics analysis for early diagnosis of OSCC. This approach was designed to overcome the limitations of a single chromatographic method due to different polarity of endogenous metabolites. As a result, 14 potential salivary metabolites were identified. Eight biomarkers up-regulated in OSCC patients are compared with control and six down-regulated groups. Receiver operating characteristic analysis was exploited to evaluate the diagnostic power of the candidate biomarkers, and related metabolic pathways have also been studied. Five salivary biomarkers (propionylcholine, N-Acetyl-L-phenylalanine, sphinganine, phytosphingosine, and S-carboxymethyl-L-cysteine) in combination yielded satisfactory accuracy (AUC = 0.997), sensitivity (100%), and specificity (96.7%) in distinguishing early stage of OSCC from the control. In this study, a comprehensive saliva metabonomics analysis for identifying potential biomarkers to early diagnose OSCC is successfully demonstrated, which has the advantages of non-invasive, simple, reliable, and low-cost. These novel metabolic biomarkers have obvious clinical utility that will help to diagnose OSCC at its early stage.

Saliva diagnostics – Current views and directions

“…33 Similarly, recently a study was carried out using hydrophilic interaction chromatography-ultraperformance LC-MS analysis reports significant differences in the concentration of choline, betaine, pipecolinic acid (high in OSCC), and L-carnitine (low in OSCC). 34 Finally, the use of a novel system in which reversed phase liquid and hydrophilic interaction chromatography were combined with TOF-MS resulted in the discovery of five new metabolic markers for OSCC, such as propionylcholine, N-acetyl-L-phenylalanine, sphinganine, phytosphingosine, and S-carboxymethyl-L-cysteine. 34 …”

“…34 Finally, the use of a novel system in which reversed phase liquid and hydrophilic interaction chromatography were combined with TOF-MS resulted in the discovery of five new metabolic markers for OSCC, such as propionylcholine, N-acetyl-L-phenylalanine, sphinganine, phytosphingosine, and S-carboxymethyl-L-cysteine. 34 …”

An untargeted metabolomics-driven approach based on LC–TOF/MS and LC–MS/MS for the screening of xenobiotics and metabolites of Zhi-Zi-Da-Huang decoction in rat plasma

“…After normalization of the intensity of each ion, the resulting three-dimensional data matrix was exported into SIMCA-P software (13.0 demo version, Umetrics, Sweden) for supervised orthogonal partial least squares discriminant analysis (OPLS-DA) [19]. OPLS-DA was carried out on data to identify discriminant t R -m/z pairs in rat plasma between the control group and ZZDHD-dosed group.…”

Salivary Metabolomics and Oral Carcinogenesis

“…Metabolomics or metabonomics can be defined as a systematic study of small molecular weight substances in cells, tissues or whole organisms as influenced by multiple factors [17] . It is one of the core disciplines of systems biology focusing on the study of low molecular weight organic and inorganic chemicals in biological system [18] .…”

“…The eight up-regulated biomarkers included lactic acid, hydroxyphenyllactic acid, N-nonanoylglycine, 5-hydroxymethyluracil, succinic acid, ornithine, hexanoylcarnitine and propionylcholine. The six downregulated biomarkers were carnitine, 4-hydroxy-L-glutamic acid, acetylphenylalanine, sphinganine, phytosphingosine and S-carboxymethyl-L-cysteine [17] .…”