Exploring Potential Diagnostic and Prognostic Salivary Biomarkers in Cancer

A special issue of Metabolites (ISSN 2218-1989). This special issue belongs to the section "Endocrinology and Clinical Metabolic Research".

Deadline for manuscript submissions: closed (31 May 2022) | Viewed by 20835

Special Issue Editors


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Guest Editor
Leicester School of Pharmacy, Faculty of Health and Life Sciences, De Montfort University, Leicester, UK
Interests: chemical pathology; clinical chemistry; NMR-based metabolomics; disease diagnosis and prognostic monitoring; metabolic pathway analysis; bioinorganic chemistry; drug design; development and synthesis; artificial intelligence; machine learning; research ethics
Special Issues, Collections and Topics in MDPI journals

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Guest Editor
Biochemistry Research Laboratory, Omsk State Pedagogical University, Omsk, Russia
Interests: salivary biomarkers; lung cancer; breast cancer; diagnosis; prognosis
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Recently, the attention of researchers to the study of human saliva as a biofluid with unique properties and diagnostic capabilities has increased. Indeed, a new term, “salivaomics”, has been proposed, which brings together knowledge about various components in saliva, including the genome, epigenome, transcript, proteome, metabolome, and microbiome. This has led to the development of new technologies and validation of a wide range of salivary biomarkers that will soon render saliva a valuable tool in clinical practice. Particular attention is paid to the search for new biomarkers and combinations of salivary biomarkers for the early diagnosis of cancer. Currently, the first steps are being taken towards evaluating the role of salivary biomarkers in the prognostic monitoring of cancer conditions. However, additional research investigations are required for the successful transfer of NMR-based salivary metabolomics to actual clinical use as a diagnostic benefit for clinicians, researchers, and patients alike. Therefore, this Special Issue is planned to include current research on the use of salivary biomarkers for the diagnosis and prognosis of cancer. Its major focus is to evaluate the future perspectives of reported observations acquired from metabolomics studies focused on evaluations of the diagnosis and prognostic tracking of salivary biomarkers for both oral and non-oral (systemic) cancers, the former including head and neck cancer, and oral cavity squamous cell and oropharyngeal squamous cell carcinomas, the latter featuring head and squamous cell, lung, breast, pancreatic and prostate cancers, among others.

Prof. Dr. Martin Grootveld
Dr. Lyudmila Bel'skaya
Guest Editors

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Keywords

  • salivary biomarkers
  • metabolomics
  • salivaomics
  • diagnosis
  • prognosis
  • cancer

Published Papers (8 papers)

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Research

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14 pages, 1057 KiB  
Article
Salivary Concentrations of Chemerin, α-Defensin 1, and TNF-α as Potential Biomarkers in the Early Diagnosis of Colorectal Cancer
by Dariusz Waniczek, Elżbieta Świętochowska, Mirosław Śnietura, Paweł Kiczmer, Zbigniew Lorenc and Małgorzata Muc-Wierzgoń
Metabolites 2022, 12(8), 704; https://doi.org/10.3390/metabo12080704 - 28 Jul 2022
Cited by 2 | Viewed by 1455
Abstract
Colorectal cancer is one of the most prevalent cancers worldwide. There is a great interest and need to find simple, inexpensive, and minimally invasive diagnostic tests. The aim of the study was to analyze the salivary concentrations of chemerin, α-defensin 1, and TNF-α [...] Read more.
Colorectal cancer is one of the most prevalent cancers worldwide. There is a great interest and need to find simple, inexpensive, and minimally invasive diagnostic tests. The aim of the study was to analyze the salivary concentrations of chemerin, α-defensin 1, and TNF-α in colorectal cancer (CRC) patients and in a healthy control group. The concentration of these proteins was simultaneously determined in the serum of subjects. We also aimed to assess the correlation of these results and selected clinicopathological features. This prospective study was comprised of 39 CRC patients and 40 control group patients. Salivary and serum concentrations were determined by enzyme immunoassays. The salivary and serum concentrations of chemerin, α-defensin 1, and TNF-α were significantly higher in cancer patients compared to the control group. No correlation was found between concentrations of the proteins and the clinical stage of cancer and tumor location. The ROC curve analysis showed that although salivary concentrations of all proteins showed 100% sensitivity and 100% specificity, serum concentrations of the analyzed proteins were characterized by 100% sensitivity and over 90% specificity. The assessment of chemerin, α-defensin 1, and TNF-α concentrations in saliva seem to have great potential as quick and useful biomarkers in the early diagnosis of CRC. Full article
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15 pages, 7093 KiB  
Article
Prognostic Value of Salivary Biochemical Indicators in Primary Resectable Breast Cancer
by Lyudmila V. Bel’skaya and Elena A. Sarf
Metabolites 2022, 12(6), 552; https://doi.org/10.3390/metabo12060552 - 16 Jun 2022
Cited by 2 | Viewed by 1514
Abstract
Despite the fact that breast cancer was detected in the early stages, the prognosis was not always favorable. In this paper, we examined the impact of clinical and pathological characteristics of patients and the composition of saliva before treatment on overall survival and [...] Read more.
Despite the fact that breast cancer was detected in the early stages, the prognosis was not always favorable. In this paper, we examined the impact of clinical and pathological characteristics of patients and the composition of saliva before treatment on overall survival and the risk of recurrence of primary resectable breast cancer. The study included 355 patients of the Omsk Clinical Oncology Center with a diagnosis of primary resectable breast cancer (T1-3N0-1M0). Saliva was analyzed for 42 biochemical indicators before the start of treatment. We have identified two biochemical indicators of saliva that can act as prognostic markers: alkaline phosphatase (ALP) and diene conjugates (DC). Favorable prognostic factors were ALP activity above 71.7 U/L and DC level above 3.93 c.u. Additional accounting for aspartate aminotransferase (AST) activity allows for forming a group with a favorable prognosis, for which the relative risk is reduced by more than 11 times (HR = 11.49, 95% CI 1.43–88.99, p = 0.01591). Salivary AST activity has no independent prognostic value. Multivariate analysis showed that tumor size, lymph nodes metastasis status, malignancy grade, tumor HER2 status, and salivary ALP activity were independent predictors. It was shown that the risk of recurrence decreased with menopause and increased with an increase in the size of the primary tumor and lymph node involvement. Significant risk factors for recurrence were salivary ALP activity below 71.7 U/L and DC levels below 3.93 c.u. before treatment. Thus, the assessment of biochemical indicators of saliva before treatment can provide prognostic information comparable in importance to the clinicopathological characteristics of the tumor and can be used to identify a risk group for recurrence in primary resectable breast cancer. Full article
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15 pages, 1564 KiB  
Article
Metabolic Features of Saliva in Breast Cancer Patients
by Lyudmila V. Bel’skaya, Elena A. Sarf, Denis V. Solomatin and Victor K. Kosenok
Metabolites 2022, 12(2), 166; https://doi.org/10.3390/metabo12020166 - 10 Feb 2022
Cited by 10 | Viewed by 2151
Abstract
The aim of the work was to study the metabolic characteristics of saliva in breast cancer and the subsequent assessment of the potential information content of its individual biochemical indicators. The study included 487 patients of the Omsk Clinical Oncology Center with morphologically [...] Read more.
The aim of the work was to study the metabolic characteristics of saliva in breast cancer and the subsequent assessment of the potential information content of its individual biochemical indicators. The study included 487 patients of the Omsk Clinical Oncology Center with morphologically verified breast cancer and 298 volunteers without breast pathologies. Saliva samples were obtained from all patients before the start of treatment, and the values of 34 biochemical indicators were determined. It has been shown that concentration of total protein, urea, uric acid (UA), the total content of α-amino acids and lipid peroxidation products, and the activity of metabolic and antioxidant enzymes (in particular catalase—CAT) of saliva changed significantly in breast cancer. Biochemical indicators characterizing early breast cancer have been identified, which can be used for timely diagnosis in addition to existing methods. The coefficients UA/Urea and UA·CAT/Urea are proposed, for which the maximum deviation from the norm was observed in the early stages of the disease. It was shown that for ductal breast cancer, changes in the activity of metabolic enzymes of saliva were more pronounced, while, for lobular breast cancer, the indicators of enzymatic and non-enzymatic components of antioxidant protection changed. The results confirmed the potential importance of saliva in the diagnosis of breast cancer. Full article
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Review

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17 pages, 1790 KiB  
Review
The New Era of Salivaomics in Dentistry: Frontiers and Facts in the Early Diagnosis and Prevention of Oral Diseases and Cancer
by Flavia Papale, Simona Santonocito, Alessandro Polizzi, Antonino Lo Giudice, Saverio Capodiferro, Gianfranco Favia and Gaetano Isola
Metabolites 2022, 12(7), 638; https://doi.org/10.3390/metabo12070638 - 12 Jul 2022
Cited by 11 | Viewed by 3891
Abstract
Nowadays, with the development of new and highly sensitive, blood is not the only medium of choice for the diagnosis of several diseases and pathological conditions. Saliva is now considered a safe and non-invasive sample to study oral and systemic diseases, showing great [...] Read more.
Nowadays, with the development of new and highly sensitive, blood is not the only medium of choice for the diagnosis of several diseases and pathological conditions. Saliva is now considered a safe and non-invasive sample to study oral and systemic diseases, showing great diagnostic potential. According to several recent studies, saliva has emerged as an emerging biofluid for the early diagnosis of several diseases, indicated as a mirror of oral and systemic health and a valuable source of clinically relevant information. Indeed, several studies have observed that saliva is useful for detecting and diagnosing malignant tumours, human immunodeficiency virus, heart disease, and autoimmune diseases. The growing realisation that saliva is an inexhaustible source of information has led to the coining of the term ‘Salivaomics’, which includes five “omics” in connection with the main constituents of saliva: genome and epigenome, transcriptomics, metabolomics, lipidomics, proteomics and microbiota. All those may be changed by disease state, so they offer significant advantages in the early diagnosis and prognosis of oral diseases. The aim of the present review isto update and highlight the new frontiers of salivaomics in diagnosing and managing oral disorders, such as periodontitis, premalignant disorders, and oral squamous cell carcinoma (OSCC). Full article
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14 pages, 2074 KiB  
Review
Salivary Metabolomics for Oral Cancer Detection: A Narrative Review
by Karthika Panneerselvam, Shigeo Ishikawa, Rajkumar Krishnan and Masahiro Sugimoto
Metabolites 2022, 12(5), 436; https://doi.org/10.3390/metabo12050436 - 12 May 2022
Cited by 14 | Viewed by 2958
Abstract
The development of low- or non-invasive screening tests for cancer is crucial for early detection. Saliva is an ideal biofluid containing informative components for monitoring oral and systemic diseases. Metabolomics has frequently been used to identify and quantify numerous metabolites in saliva samples, [...] Read more.
The development of low- or non-invasive screening tests for cancer is crucial for early detection. Saliva is an ideal biofluid containing informative components for monitoring oral and systemic diseases. Metabolomics has frequently been used to identify and quantify numerous metabolites in saliva samples, serving as novel biomarkers associated with various conditions, including cancers. This review summarizes the recent applications of salivary metabolomics in biomarker discovery in oral cancers. We discussed the prevalence, epidemiologic characteristics, and risk factors of oral cancers, as well as the currently available screening programs, in India and Japan. These data imply that the development of biomarkers by itself is inadequate in cancer detection. The use of current diagnostic methods and new technologies is necessary for efficient salivary metabolomics analysis. We also discuss the gap between biomarker discovery and nationwide screening for the early detection of oral cancer and its prevention. Full article
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Other

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40 pages, 3731 KiB  
Commentary
Updates and Original Case Studies Focused on the NMR-Linked Metabolomics Analysis of Human Oral Fluids Part II: Applications to the Diagnosis and Prognostic Monitoring of Oral and Systemic Cancers
by Martin Grootveld, Benita C. Percival, Georgina Page, Kayleigh Hunwin, Mohammed Bhogadia, Wyman Chan and Mark Edgar
Metabolites 2022, 12(9), 778; https://doi.org/10.3390/metabo12090778 - 24 Aug 2022
Cited by 5 | Viewed by 1858
Abstract
Human saliva offers many advantages over other biofluids regarding its use and value as a bioanalytical medium for the identification and prognostic monitoring of human diseases, mainly because its collection is largely non-invasive, is relatively cheap, and does not require any major clinical [...] Read more.
Human saliva offers many advantages over other biofluids regarding its use and value as a bioanalytical medium for the identification and prognostic monitoring of human diseases, mainly because its collection is largely non-invasive, is relatively cheap, and does not require any major clinical supervision, nor supervisory input. Indeed, participants donating this biofluid for such purposes, including the identification, validation and quantification of surrogate biomarkers, may easily self-collect such samples in their homes following the provision of full collection details to them by researchers. In this report, the authors have focused on the applications of metabolomics technologies to the diagnosis and progressive severity monitoring of human cancer conditions, firstly oral cancers (e.g., oral cavity squamous cell carcinoma), and secondly extra-oral (systemic) cancers such as lung, breast and prostate cancers. For each publication reviewed, the authors provide a detailed evaluation and critical appraisal of the experimental design, sample size, ease of sample collection (usually but not exclusively as whole mouth saliva (WMS)), their transport, length of storage and preparation for analysis. Moreover, recommended protocols for the optimisation of NMR pulse sequences for analysis, along with the application of methods and techniques for verifying and resonance assignments and validating the quantification of biomolecules responsible, are critically considered. In view of the authors’ specialisms and research interests, the majority of these investigations were conducted using NMR-based metabolomics techniques. The extension of these studies to determinations of metabolic pathways which have been pathologically disturbed in these diseases is also assessed here and reviewed. Where available, data for the monitoring of patients’ responses to chemotherapeutic treatments, and in one case, radiotherapy, are also evaluated herein. Additionally, a novel case study featured evaluates the molecular nature, levels and diagnostic potential of 1H NMR-detectable salivary ‘acute-phase’ glycoprotein carbohydrate side chains, and/or their monomeric saccharide derivatives, as biomarkers for cancer and inflammatory conditions. Full article
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16 pages, 1121 KiB  
Systematic Review
Salivary Melatonin Changes in Oncological Patients: A Systematic Review
by Kacper Nijakowski, Michał Surdacki and Małgorzata Sobieszczańska
Metabolites 2022, 12(5), 439; https://doi.org/10.3390/metabo12050439 - 13 May 2022
Cited by 4 | Viewed by 2063
Abstract
Melatonin is known as a regulator of circadian sleep and waking rhythm. This hormone secreted by the pineal gland also has protective, oncostatic, and antioxidant properties. This systematic review was designed to answer the question “Is there a relationship between salivary melatonin changes [...] Read more.
Melatonin is known as a regulator of circadian sleep and waking rhythm. This hormone secreted by the pineal gland also has protective, oncostatic, and antioxidant properties. This systematic review was designed to answer the question “Is there a relationship between salivary melatonin changes and oncological diseases?”. Following the inclusion and exclusion criteria, ten studies were included, according to PRISMA statement guidelines. In all included studies, the diagnostic material was unstimulated whole saliva, in which the melatonin changes were determined by different laboratory methods. Most studies concerned changes in melatonin levels in patients with brain tumours due to a direct effect on the circadian rhythm centres. Other studies focused on disorders of melatonin secretion and its inclusion as a diagnostic marker in patients with prostate cancer and oral squamous cell carcinoma. The association between melatonin changes and sleep quality and chronotype in patients with newly diagnosed lung cancer and lymphoma survivors was also investigated. In conclusion, our systematic review may suggest trends for melatonin secretion alterations in oncological patients. However, due to the significant heterogeneity of the included reports, it is not possible to clearly determine a link between changes in salivary melatonin levels and the oncological diagnosis. Full article
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17 pages, 1128 KiB  
Systematic Review
Salivary Metabolomics for Oral Squamous Cell Carcinoma Diagnosis: A Systematic Review
by Kacper Nijakowski, Dawid Gruszczyński, Dariusz Kopała and Anna Surdacka
Metabolites 2022, 12(4), 294; https://doi.org/10.3390/metabo12040294 - 26 Mar 2022
Cited by 26 | Viewed by 3871
Abstract
Oral squamous cell carcinoma (OSCC) is the most common type of oral cancer in which the consumption of tobacco and alcohol is considered to be the main aetiological factor. Salivary metabolome profiling could identify novel biochemical pathways involved in the pathogenesis of various [...] Read more.
Oral squamous cell carcinoma (OSCC) is the most common type of oral cancer in which the consumption of tobacco and alcohol is considered to be the main aetiological factor. Salivary metabolome profiling could identify novel biochemical pathways involved in the pathogenesis of various diseases. This systematic review was designed to answer the question “Are salivary metabolites reliable for the diagnosis of oral squamous cell carcinoma?”. Following the inclusion and exclusion criteria, nineteen studies were included (according to PRISMA statement guidelines). In all included studies, the diagnostic material was unstimulated whole saliva, whose metabolome changes were determined by different spectroscopic methods. At the metabolic level, OSCC patients differed significantly not only from healthy subjects but also from patients with oral leukoplakia, lichen planus or other oral potentially malignant disorders. Among the detected salivary metabolites, there were the indicators of the impaired metabolic pathways, such as choline metabolism, amino acid pathways, polyamine metabolism, urea cycle, creatine metabolism, glycolysis or glycerolipid metabolism. In conclusion, saliva contains many potential metabolites, which can be used reliably to early diagnose and monitor staging in patients with OSCC. However, further investigations are necessary to confirm these findings and to identify new salivary metabolic biomarkers. Full article
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