Differential diagnosis of lung cancer and benign lung lesion using salivary metabolites: A preliminary study

Abstract

Background: Saliva is often used as a biomarker for the diagnosis of some oral and systematic diseases, owing to the non-invasive attribute of the fluid. In this study, we aimed to identify salivary biomarkers for distinguishing lung cancer (LC) from benign lung lesion (BLL).

Materials and methods: Unstimulated saliva samples were collected from 41 patients with LC and 21 with BLL. Salivary metabolites were comprehensively analyzed using capillary electrophoresis mass spectrometry. To differentiate between patients with LCs and BLLs, the discriminatory ability of each biomarker was assessed. Furthermore, a multiple logistic regression (MLR) model was developed for evaluating discriminatory ability of each salivary metabolite.

Results: The profiles of 10 salivary metabolites were remarkably different between the LC and BLL samples. Among them, the concentration of salivary tryptophan was significantly lower in the samples from patients with LC than in those from patients with BLL, and the area under the curve (AUC) for discriminating patients with LC from those with BLL was 0.663 (95% confidence interval [CI] = 0.516-0.810, p = 0.036). Furthermore, from the MLR model developed using these metabolites, diethanolamine, cytosine, lysine, and tyrosine, were selected using the back-selection regression method. The MLR model based on these four metabolites had a high discriminatory ability for patients with LC and those with BLL (AUC = 0.729, 95% CI = 0.598-0.861, p = 0.003).

Conclusion: The four salivary metabolites can serve as potential non-invasive biomarkers for distinguishing LC from BLL.

Keywords: benign lung lesion; lung cancer; metabolites; saliva.

FIGURE 1

Heatmap of 10 salivary metabolomic profiles. The heatmap depicts the differences between the LC and BLL groups (p < 0.15, Mann–Whitney U‐test). Colors represent concentration of individual metabolites divided by the z‐score of the LC and BLL salivary samples. Red and blue represent higher and lower concentrations, respectively. The vertical axis indicates the number of patients. The LC group is indicated to the left of the yellow line and the BLL group to the right of the yellow line. The horizontal axis indicates the salivary metabolites. BLL, benign lung lesion; LC, lung cancer

FIGURE 2

Receiver operating characteristic (ROC) curves of tryptophan (Trp) and the multiple logistic regression (MLR) models based on the salivary concentration of diethanolamine, cytosine, lysine, and tyrosine for their discriminatory ability between patients with LC from those with BLL. The area under the curve (AUC) is 0.663 (95% CI = 0.516–0.810; p = 0.036) and 0.729 (95% CI = 0.598–0.861; p = 0.003) respectively. BLL, benign lung lesion; LC, lung cancer