Biochemical Markers of Saliva in Lung Cancer: Diagnostic and Prognostic Perspectives

Abstract

The aim of the work is to study the metabolic characteristics of saliva in lung cancer for use in early diagnosis and determining the prognosis of the disease. The patient group included 425 lung cancer patients, 168 patients with non-cancerous lung diseases, and 550 healthy volunteers. Saliva samples were collected from all participants in the experiment before treatment and 34 biochemical saliva parameters were determined. Participants were monitored for six years to assess survival rates. The statistical analysis was performed by means of Statistica 10.0 (StatSoft) program and R package (version 3.2.3). To construct the classifier, the Random Forest method was used; the classification quality was assessed using the cross-validation method. Prognostic factors were analyzed by multivariate analysis using Cox’s proportional hazard model in a backward step-wise fashion to adjust for potential confounding factors. A complex of metabolic changes occurring in saliva in lung cancer is described. Seven biochemical parameters were identified (catalase, triene conjugates, Schiff bases, pH, sialic acids, alkaline phosphatase, chlorides), which were used to construct the classifier. The sensitivity and specificity of the method were 69.5% and 87.5%, which is practically not inferior to the diagnostic characteristics of markers routinely used in the diagnosis of lung cancer. Significant independent factors in the poor prognosis of lung cancer are imidazole compounds (ICs) above 0.478 mmol/L and salivary lactate dehydrogenase activity below 545 U/L. Saliva has been shown to have great potential for the development of diagnostic and prognostic tests for lung cancer.

Salivary Metabolic Profile of Patients with Lung Cancer, Chronic Obstructive Pulmonary Disease of Varying Severity and Their Comorbidity: A Preliminary Study

“…Until now, no biomarker has been identified that would unequivocally determine the presence of lung cancer and/or COPD using both sputum and exhaled air and blood serum [ 11 , 12 , 13 ]. In previous studies, including ours, we have shown that the composition of saliva reflects metabolic changes occurring against the background of lung cancer [ 14 , 15 , 16 ]. However, a study of the effects of the combined pathology of lung cancer and COPD on the metabolic profile of saliva has not yet been conducted.…”

“…Collection of saliva samples was carried out on an empty stomach after rinsing the mouth with water in the interval of 8–10 am by spitting into sterile polypropylene tubes; the salivation rate (mL/min) was calculated. Saliva samples were centrifuged (10,000× g for 10 min) (CLb-16, Moscow, Russia), after which biochemical analysis was immediately performed without storage and freezing using the StatFax 3300 semi-automatic biochemical analyzer [ 16 ].…”

Diagnostic and Prognostic Value of Salivary Biochemical Markers in Oral Squamous Cell Carcinoma

“…Saliva samples were centrifuged (10,000× g for 10 min) (CLb-16, Moscow, Russia). Biochemical analysis of saliva was performed immediately without storage and freezing [ 37 ].…”

Features of the Metabolic Profile of Saliva in Lung Cancer and COPD: The Effect of Smoking Status

“…Saliva can be used to assess the metabolic changes that occur in lung cancer and COPD [ 17 , 18 ]. Saliva is an easily collected, non-invasive biological fluid for the diagnosis of diseases, including lung cancer [ 19 ].…”

“…Previously, we identified 34 biochemical parameters of saliva, which statistically significantly change in lung cancer of various histological types in comparison with healthy controls [ 17 ]. We have previously shown that the presence of COPD as a concomitant pathology does not fundamentally change the metabolic profile of saliva but increases the range of changes in the corresponding biochemical indicators [ 29 ].…”