Differentially regulated saliva proteome and metabolome: a way forward for risk-assessment of oral cancer among tobacco abusers

Oral cancer (OC) is a malignant tumour with high morbidity and mortality. Significant contributory factors include alcohol and tobacco abuse that dysregulate the proteome and metabolome. We assessed saliva as a noninvasive bio-sample to understand the changes in proteome and metabolome in OC, tobacco abusers (TA), and controls. OC, TA, and control samples (<i>n</i> = 22, 21, and 21, respectively) were subjected to LFQ-proteomics and NMR-based metabolomics analyses individually and integrated using systems biology; 292 out of 758 proteins with two or more unique peptides were significantly differently regulated. Functional annotation revealed that differentially expressed proteins are involved in important cellular metabolic processes. PLS-DA in metabolomics separated OC from the control and TA, and <i>K</i>-means clustering of proteomics and metabolomics profiles revealed distinguishing proteins and metabolites in OC, TA, and the control. Integrated analysis revealed convergence on molecules like transketolase (TKTT), transaldolase (TALDO), kallikrein 1 (KLK1), enolase A (ENOA), glucose-6-phosphate isomerase (G6PI), and aldolase A and C (ALDOA and ALDOC). Finally, the characteristic discriminatory features of several clusters between OC, TA, and the control remain valid only among high tobacco abusers. The results reveal metabolites that could serve as early indicators for OC, especially among chewing tobacco abusers, and therefore establish the basis for larger cohort studies to develop them as predictive OC biomarkers.