Low Abundance Proteins in Biological Fluids of Oral Diseases: A Narrative Review

This narrative review critically evaluates the biological and technical challenges associated with the identification of low-abundance proteins in selected oral diseases. A structured literature search was performed using Web of Science, EBSCOHost (Dentistry and Oral Sciences), and PubMed databases, supplemented by manual searches. Only original proteomics research articles investigating low-abundance proteins within biological fluids of oral diseases were included. Secondary literature and non-proteomic studies were excluded. A total of 42 studies were included, encompassing five oral diseases: periodontitis, oral squamous cell carcinoma (OSCC), oral lichen planus (OLP), dental caries, and medication-related osteonecrosis of the jaw (MRONJ). Periodontitis was the most extensively investigated condition, whereas MRONJ was the least studied. Among the included studies, 21 evaluated biomarkers of disease activity, 16 investigated diagnostic biomarkers, three assessed disease monitoring biomarkers, three evaluated treatment response biomarkers, and three investigated prognostic biomarkers. Across the biological fluids analysed, the majority of the identified low-abundance proteins were pro-inflammatory cytokines. Clinical evidence regarding low-abundance protein biomarkers for oral diseases is steadily emerging. However, high-quality studies with larger sample sizes are necessary to validate the diagnostic and prognostic efficacy of the proteins identified. The identification of specific protein biomarkers may significantly enhance diagnostic accuracy and prognostic monitoring, allowing clinicians to implement more effective and timely treatment strategies for patients.