EXPLORING SALIVA BIOMARKERS FOR NON-INVASIVE DIAGNOSIS OF MILD TRAUMATIC BRAIN INJURY: A SYSTEMATIC REVIEW AND META-ANALYSIS OF TRANSCRIPTOMIC-DATA

Abstract

Background: Mild traumatic brain injury (mTBI) is a prevalent injury characterized by diverse signs, symptoms, and neurological impairments that evolve over time. Clinical diagnosis of mTBI typically involves symptom reports and domain-specific testing, which are limited by their subjective nature, reliance on pre-injury comparisons, and variability in timing and type of test administration. Identifying objective biomarkers for mTBI could enable earlier and more accurate diagnosis, improving assessment and treatment. Emerging research highlights the potential of salivary protein biomarkers and differentially expressed genes from transcriptomic studies in advancing mTBI diagnostics. Objective: The study objective is to identify potential salivary biomarkers for mTBI diagnosis by integrating evidence from systematic review of observational studies and meta-analysis of transcriptomic datasets Methods: A comprehensive search was conducted across PubMed, Embase, and Google Scholar databases to identify observational studies evaluating the diagnostic utility of salivary protein biomarkers. Additionally, NCBI GEO was searched for transcriptomic datasets relating to mTBI. Seven studies met the inclusion criteria for systematic review, while two transcriptomic datasets were included in the meta-analysis. Results: The study identified 49 salivary proteins from the systematic review with significant differential expression. Subgroup analysis based on injury mechanism revealed four overlapping proteins: ALOX5, ITGB2, ADRB2, and HRH1. Furthermore, transcriptomic meta-analysis identified the presence of 1,633 differentially expressed genes among individuals with mTBI and healthy control, with 10 genes (LCN1, TMEM59L, CSKMT, ELOA3P, UTS2R, CEP126, NECTIN4, MELTF, CNFN, and RHEX) demonstrating the most significant expression changes (FDR <0.05). Conclusion: These findings underscore the presence of differential gene expression in mTBI and the potential relevance of salivary proteins for objective identification of mTBI.