An established target of medicine and modern healthcare is early diagnosis of diseases and the evaluation of patient risk profile. Detect a disease at an early stage and modulate the risk factors may improve the success of treatment, prevent complications and enhance prognosis and quality of life of patients. The possibility to obtain an accurate diagnosis and effective screenings through reliable and non-invasive tools, seems to be a very attractive. Within such background, the concept of “precision medicine” is rapidly developing. It usually employs molecular profiles to adapt a therapeutic strategy to a patient, with specific stage of disease and/or to determine the predisposition for. “Precision medicine” is based on biomolecular disciplines usually indicated with the suffix “omics”. It encompasses genomic, epigenomic, transcriptomic, proteomic, metabolomic, and others. The combination of the above-mentioned concepts is leading to the development of novel technologies, based on easy and non-invasive methods to collect diagnostic human specimens, possibly with a high specificity and sensitivity and customized for specific patient. One of the human fluids which has gained importance within this context is saliva. The aim of the present thesis is to present translational data about salivary biomarkers and their potential application in clinical setting. An update of the current knowledge about salivary diagnostics is provided in Chapter 1. Latest literature confirms the fluid high potential as a matrix for multipurpose analysis with several different technological platforms; the number of recently published studies confirms the increasing interest in saliva. However, as routinely reliable diagnostic tools, salivary diagnostics has still little spreading. Chapter 2 reports preliminary data of a pilot study of nutriepigenomic, which aims to highlight the role of nutrition in epigenetic variations (induced and inducible), as cause of cancer risk increasing or decreasing. The study evaluated the effect of a nutritional and lifestyle program [Nutritional and Lifestyle Intervention (NLI)] on salivary miRNAs expression in women carriers of BRCA1/2 germ mutations. Preliminary statistically results seem to demonstrate that 5 salivary miRNAs have a statistical difference between their expression before nutritional intervention and after 18 months. The progression from normal mucosa to different grades of dysplasia is explored in relation to salivary metabolome in an experimental case-control study (Chapter 3). Metabolomics was performed on saliva samples using high resolution 1H-NMR (Nuclear Magnetic Resonance). A cohort of voluntary patients with histologically confirmed oral leukoplakia and oral lichen planus was enrolled and salivary specimens were collected before surgical procedures (incisional/excisional biopsies). Preliminary results are focused on the differences between metabolomes of patients with dysplastic and non-dysplastic leukoplakia as well as healthy controls. Chapter 4 reports data about the possible relationships between the salivary and serum metabolomes to gain a comprehensive view of the metabolic phenotype under physiological conditions. Using 1H-NMR spectroscopy, we obtained the serum metabolite profiles of 20 healthy young individuals and compared them with the metabolomes of parotid, submandibular/sublingual, and whole saliva samples collected concurrently from the same individuals. The salivary gland-specific metabolic composition and the effective saliva collection protocol is reported in the Annex n° 1. During the samples collection, the Full-Mouth Bleeding Score (FMBS) was employed as a classification parameter. We identified a panel of metabolites differentially expressed in healthy subjects with high but physiological FMBS scores compared to those with lower score, and this set of metabolites may be associated with early stages of gingival inflammation. This correlation between salivary metabolites and gingival bleeding score is described in Chapter 5. The salivary fluid has been widely studied and genomic, transcriptomic, and proteomic profiles have been reported. Conversely, its metabolic composition is still mainly unknown: metabolites in submandibular/sublingual saliva have never been analyzed systematically. These results could provide basis to a further identification of salivary biomarkers in oral and systemic diseases. Results emerging from 2 systematic reviews are presented in chapter 6 and 7. The first was developed to answer the question: “Are salivary biomarkers reliable for diagnosis of dental caries?” (Chapter 6), while the second aims to identify the salivary metabolites for the diagnosis of oral cancer (Chapter 7). For both reviews, results and quality assessment of selected studies are presented, highlighting the potential risks of bias in current literature. Moreover, a summary of statistical data and reported evidence are given. In conclusion, the researches described in this thesis highlight that there are many advantages to use saliva as a diagnostic fluid for monitoring health and diseases.

Identification and validation of salivary biomarkers for systemic and oral diseases

Rita, Antonelli
2025

Abstract

An established target of medicine and modern healthcare is early diagnosis of diseases and the evaluation of patient risk profile. Detect a disease at an early stage and modulate the risk factors may improve the success of treatment, prevent complications and enhance prognosis and quality of life of patients. The possibility to obtain an accurate diagnosis and effective screenings through reliable and non-invasive tools, seems to be a very attractive. Within such background, the concept of “precision medicine” is rapidly developing. It usually employs molecular profiles to adapt a therapeutic strategy to a patient, with specific stage of disease and/or to determine the predisposition for. “Precision medicine” is based on biomolecular disciplines usually indicated with the suffix “omics”. It encompasses genomic, epigenomic, transcriptomic, proteomic, metabolomic, and others. The combination of the above-mentioned concepts is leading to the development of novel technologies, based on easy and non-invasive methods to collect diagnostic human specimens, possibly with a high specificity and sensitivity and customized for specific patient. One of the human fluids which has gained importance within this context is saliva. The aim of the present thesis is to present translational data about salivary biomarkers and their potential application in clinical setting. An update of the current knowledge about salivary diagnostics is provided in Chapter 1. Latest literature confirms the fluid high potential as a matrix for multipurpose analysis with several different technological platforms; the number of recently published studies confirms the increasing interest in saliva. However, as routinely reliable diagnostic tools, salivary diagnostics has still little spreading. Chapter 2 reports preliminary data of a pilot study of nutriepigenomic, which aims to highlight the role of nutrition in epigenetic variations (induced and inducible), as cause of cancer risk increasing or decreasing. The study evaluated the effect of a nutritional and lifestyle program [Nutritional and Lifestyle Intervention (NLI)] on salivary miRNAs expression in women carriers of BRCA1/2 germ mutations. Preliminary statistically results seem to demonstrate that 5 salivary miRNAs have a statistical difference between their expression before nutritional intervention and after 18 months. The progression from normal mucosa to different grades of dysplasia is explored in relation to salivary metabolome in an experimental case-control study (Chapter 3). Metabolomics was performed on saliva samples using high resolution 1H-NMR (Nuclear Magnetic Resonance). A cohort of voluntary patients with histologically confirmed oral leukoplakia and oral lichen planus was enrolled and salivary specimens were collected before surgical procedures (incisional/excisional biopsies). Preliminary results are focused on the differences between metabolomes of patients with dysplastic and non-dysplastic leukoplakia as well as healthy controls. Chapter 4 reports data about the possible relationships between the salivary and serum metabolomes to gain a comprehensive view of the metabolic phenotype under physiological conditions. Using 1H-NMR spectroscopy, we obtained the serum metabolite profiles of 20 healthy young individuals and compared them with the metabolomes of parotid, submandibular/sublingual, and whole saliva samples collected concurrently from the same individuals. The salivary gland-specific metabolic composition and the effective saliva collection protocol is reported in the Annex n° 1. During the samples collection, the Full-Mouth Bleeding Score (FMBS) was employed as a classification parameter. We identified a panel of metabolites differentially expressed in healthy subjects with high but physiological FMBS scores compared to those with lower score, and this set of metabolites may be associated with early stages of gingival inflammation. This correlation between salivary metabolites and gingival bleeding score is described in Chapter 5. The salivary fluid has been widely studied and genomic, transcriptomic, and proteomic profiles have been reported. Conversely, its metabolic composition is still mainly unknown: metabolites in submandibular/sublingual saliva have never been analyzed systematically. These results could provide basis to a further identification of salivary biomarkers in oral and systemic diseases. Results emerging from 2 systematic reviews are presented in chapter 6 and 7. The first was developed to answer the question: “Are salivary biomarkers reliable for diagnosis of dental caries?” (Chapter 6), while the second aims to identify the salivary metabolites for the diagnosis of oral cancer (Chapter 7). For both reviews, results and quality assessment of selected studies are presented, highlighting the potential risks of bias in current literature. Moreover, a summary of statistical data and reported evidence are given. In conclusion, the researches described in this thesis highlight that there are many advantages to use saliva as a diagnostic fluid for monitoring health and diseases.
Identification and validation of salivary biomarkers for systemic and oral diseases
9-mag-2025
ENG
Salivary diagnostic
Salivary biomarkers
MEDS-16/A
Marco, Meleti
Università degli Studi di Parma. Dipartimento di Medicina e chirurgia
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/20.500.14242/213394
Il codice NBN di questa tesi è URN:NBN:IT:UNIPR-213394