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Hu CC, Wang SG, Gao Z, Qing MF, Pan S, Liu YY, Li F. Emerging salivary biomarkers for early detection of oral squamous cell carcinoma. World J Clin Oncol 2025; 16:103803. [PMID: 40290680 PMCID: PMC12019256 DOI: 10.5306/wjco.v16.i4.103803] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/02/2024] [Revised: 01/23/2025] [Accepted: 03/06/2025] [Indexed: 03/26/2025] Open
Abstract
Oral cancer, particularly oral squamous cell carcinoma (OSCC), remains a leading cause of cancer-related morbidity and mortality, with delayed diagnosis being a major contributing factor. Although salivary biomarkers have been explored for over three decades, the need for reliable, non-invasive diagnostic methods that enable early detection and continuous monitoring of OSCC remains unmet. This review aims to provide an updated overview of the latest advancements in salivary biomarker research, focusing on emerging biomarkers such as interleukin-6, interleukin-8, microRNAs and DNA methylation patterns, as well as metabolites and microbiota, all of which show significant promise for early OSCC detection. In addition to discussing well-established biomarkers, we explore recent technological developments that increase the sensitivity and specificity of these biomarkers, such as mass spectrometry, multiplex assays, and nanobiosensors. These developments are complemented by the integration of artificial intelligence for data analysis, which enables more accurate, point-of-care diagnostics that could revolutionize oral cancer screening. This review not only consolidates current knowledge but also addresses the challenges that hinder the widespread clinical adoption of salivary diagnostics, such as saliva variability and assay standardization. By overcoming these barriers, salivary biomarker-based diagnostics have the potential to transform OSCC detection, offering a non-invasive, cost-effective solution that can improve early diagnosis and patient outcomes.
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Affiliation(s)
- Cheng-Chen Hu
- Department of Stomatology, The Second Affiliated Hospital of Chongqing Medical University, Chongqing 400010, China
| | - Sheng-Guo Wang
- Department of Stomatology, The Second Affiliated Hospital of Chongqing Medical University, Chongqing 400010, China
| | - Zhi Gao
- Department of Stomatology, The Second Affiliated Hospital of Chongqing Medical University, Chongqing 400010, China
| | - Mao-Feng Qing
- Department of Stomatology, The Second Affiliated Hospital of Chongqing Medical University, Chongqing 400010, China
| | - Shan Pan
- Department of Stomatology, The Second Affiliated Hospital of Chongqing Medical University, Chongqing 400010, China
| | - Ying-Ying Liu
- Department of Stomatology, The Second Affiliated Hospital of Chongqing Medical University, Chongqing 400010, China
| | - Fang Li
- Department of General Surgery, Chongqing General Hospital, Chongqing 401147, China
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Tang JW, Mou JY, Chen J, Yuan Q, Wen XR, Liu QH, Liu Z, Wang L. Discrimination of Benign and Malignant Thyroid Nodules through Comparative Analyses of Human Saliva Samples via Metabolomics and Deep-Learning-Guided Label-free SERS. ACS APPLIED MATERIALS & INTERFACES 2025; 17:5538-5549. [PMID: 39772412 DOI: 10.1021/acsami.4c20503] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/11/2025]
Abstract
Thyroid nodules are a very common entity. The overall prevalence in the populace is estimated to be around 65-68%, among which a small portion (less than 5%) is malignant (cancerous). Therefore, it is important to discriminate benign thyroid nodules from malignant thyroid nodules. In this study, an equal number of participants with benign and malignant thyroid nodules (N = 10/group) were recruited. Saliva samples were collected from each participant, and SERS spectra were acquired, followed by validation using a metabolomics approach. An additional equal number of patients (N = 40/group) were recruited to construct diagnostic models. The performance of various machine learning (ML) algorithms was assessed using multiple evaluation metrics. Finally, the reliability of the optimal model was tested using blind test data (N = 10/group for benign and malignant thyroid nodules). The results showed a consistent trend between the SERS metabolic profile and the metabolites identified through MS analysis. The Multi-ResNet algorithm was optimal, achieving a 95% accuracy in sample discrimination. Additionally, blind test data sets yielded an overall accuracy of 83%. In summary, the deep-learning-guided SERS technique holds great potential in the accurate discrimination of benign and malignant thyroid nodules via human saliva samples, which facilitates the noninvasive diagnosis of malignant thyroid nodules in clinical settings.
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Affiliation(s)
- Jia-Wei Tang
- Laboratory Medicine, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, Guangdong Province 510080, China
| | - Jing-Yi Mou
- Department of Breast Surgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, China
| | - Jie Chen
- Laboratory Medicine, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, Guangdong Province 510080, China
| | - Quan Yuan
- Department of Intelligent Medical Engineering, School of Medical Informatics and Engineering, Xuzhou Medical University, Xuzhou, Jiangsu Province 210000, China
| | - Xin-Ru Wen
- Department of Intelligent Medical Engineering, School of Medical Informatics and Engineering, Xuzhou Medical University, Xuzhou, Jiangsu Province 210000, China
| | - Qing-Hua Liu
- State Key Laboratory of Quality Research in Chinese Medicines, Macau University of Science and Technology, Taipa, Macao Special Administrative Region of China 999078, China
| | - Zhao Liu
- Department of Thyroid and Breast Surgery, Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu Province 210000, China
- Department of Clinical Medicine, School of first Clinical Medicine, Xuzhou Medical University, Xuzhou, Jiangsu Province 210000, China
| | - Liang Wang
- Laboratory Medicine, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, Guangdong Province 510080, China
- Division of Microbiology and Immunology, School of Biomedical Sciences, University of Western Australia, Crawley, Western Australia 6009, Australia
- The Center for Precision Health, School of Medical and Health Sciences, Edith Cowan University, Joondalup, Western Australia 6027, Australia
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López-Pintor RM, González-Serrano J, Vallina C, Ivaylova Serkedzhieva K, Virto L, Nuevo P, Caponio VCA, Iniesta M, Rodríguez Santamarta T, Lequerica Fernández P, Iglesias Velázquez Ó, Hernández G, de Vicente JC. Factors influencing salivary lactate dehydrogenase levels in oral squamous cell carcinoma and oral potentially malignant disorders. FRONTIERS IN ORAL HEALTH 2025; 5:1525936. [PMID: 39839666 PMCID: PMC11747469 DOI: 10.3389/froh.2024.1525936] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/10/2024] [Accepted: 12/13/2024] [Indexed: 01/23/2025] Open
Abstract
Introduction Salivary Lactate Dehydrogenase (sLDH) levels seem to be higher in patients with Oral Squamous Cell Carcinoma (OSCC) and Oral Potentially Malignant Disorders (OPMD) than a control group (CG). Methods Case-control study. Patients with OPMD [oral leukoplakia (OL) and oral lichen planus (OLP)] and OSCC who attended two services in Spain were selected. sLDH in saliva was measured. Epidemiological, periodontal and specific variables related to OPMD and OSCC were collected. Results A total of 92 patients were included: 12 with OSCC, 51 with OPMD (17 OL and 34 OLP), and 29 controls. sLDH values were higher in the OSCC, followed by the OPMD and CG groups, although no significant differences were observed. In the OSCC group, larger tumor size was associated with higher sLDH levels. In the OLP group, sLDH values were higher in patients with symptomatic lesions than in patients with only white lesions, but not significantly. No associations were observed between sLDH and the type of OL (homogeneous vs. non-homogeneous) and the degree of dysplasia. When analyzing periodontal variables among OSCC, OPMD and CG, periodontal probing depth (PPD) and bleeding on probing were significantly higher in the OSCC group, while the plaque index was higher in OPMD patients. The linear regression model for sLDH in the total group identified age and PPD as significant predictors of sLDH levels. Discussion Although sLDH values were higher in OSCC and OPMD patients than in a CG, the results do not support the use of sLDH as a reliable prognostic biomarker of malignancy. Future studies need to consider other factors that may influence sLDH levels, such as age and periodontal status.
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Affiliation(s)
- Rosa María López-Pintor
- Department of Dental Clinical Specialties, Faculty of Dentistry, Complutense University, Madrid, Spain
- ORALMED Research Group, Department of Dental Clinical Specialties, School of Dentistry, Complutense University, Madrid, Spain
| | - José González-Serrano
- Department of Dental Clinical Specialties, Faculty of Dentistry, Complutense University, Madrid, Spain
- ORALMED Research Group, Department of Dental Clinical Specialties, School of Dentistry, Complutense University, Madrid, Spain
| | - Carmen Vallina
- Department of Dental Clinical Specialties, Faculty of Dentistry, Complutense University, Madrid, Spain
| | - Katerina Ivaylova Serkedzhieva
- Department of Dental Clinical Specialties, Faculty of Dentistry, Complutense University, Madrid, Spain
- ORALMED Research Group, Department of Dental Clinical Specialties, School of Dentistry, Complutense University, Madrid, Spain
| | - Leire Virto
- Department of Anatomy and Embryology, Faculty of Optics and Optometry, Complutense University, Madrid, Spain
| | - Paula Nuevo
- Research Laboratory, Faculty of Dentistry, Complutense University, Madrid, Spain
| | - Vito Carlo Alberto Caponio
- ORALMED Research Group, Department of Dental Clinical Specialties, School of Dentistry, Complutense University, Madrid, Spain
- Department of Clinical and Experimental Medicine, University of Foggia, Foggia, Italy
| | - Margarita Iniesta
- Department of Dental Clinical Specialties, Faculty of Dentistry, Complutense University, Madrid, Spain
| | - Tania Rodríguez Santamarta
- Department of Oral and Maxillofacial Surgery, Hospital Universitario Central de Asturias (HUCA), Oviedo, Spain
| | | | - Óscar Iglesias Velázquez
- Department of Dental Clinical Specialties, Faculty of Dentistry, Complutense University, Madrid, Spain
- ORALMED Research Group, Department of Dental Clinical Specialties, School of Dentistry, Complutense University, Madrid, Spain
| | - Gonzalo Hernández
- Department of Dental Clinical Specialties, Faculty of Dentistry, Complutense University, Madrid, Spain
- ORALMED Research Group, Department of Dental Clinical Specialties, School of Dentistry, Complutense University, Madrid, Spain
| | - Juan Carlos de Vicente
- ORALMED Research Group, Department of Dental Clinical Specialties, School of Dentistry, Complutense University, Madrid, Spain
- Department of Oral and Maxillofacial Surgery, Hospital Universitario Central de Asturias (HUCA), Oviedo, Spain
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Ebersole JL, Hasturk H, Huber M, Gellibolian R, Markaryan A, Zhang XD, Miller CS. Realizing the clinical utility of saliva for monitoring oral diseases. Periodontol 2000 2024; 95:203-219. [PMID: 39010260 DOI: 10.1111/prd.12581] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/18/2024] [Revised: 05/01/2024] [Accepted: 05/16/2024] [Indexed: 07/17/2024]
Abstract
In the era of personalized/precision health care, additional effort is being expended to understand the biology and molecular mechanisms of disease processes. How these mechanisms are affected by individual genetics, environmental exposures, and behavioral choices will encompass an expanding role in the future of optimally preventing and treating diseases. Considering saliva as an important biological fluid for analysis to inform oral disease detection/description continues to expand. This review provides an overview of saliva as a diagnostic fluid and the features of various biomarkers that have been reported. We emphasize the use of salivary biomarkers in periodontitis and transport the reader through extant literature, gaps in knowledge, and a structured approach toward validating and determine the utility of biomarkers in periodontitis. A summation of the findings support the likelihood that a panel of biomarkers including both host molecules and specific microorganisms will be required to most effectively identify risk for early transition to disease, ongoing disease activity, progression, and likelihood of response to standard periodontal therapy. The goals would be to develop predictive algorithms that serve as adjunctive diagnostic tools which provide the clinician and patient important information for making informed clinical decisions.
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Affiliation(s)
- Jeffrey L Ebersole
- Department of Biomedical Sciences, School of Dental Medicine, University of Nevada Las Vegas, Las Vegas, Nevada, USA
| | - Hatice Hasturk
- Immunology and Inflammation, Center for Clinical and Translational Research, The ADA Forsyth Institute, Cambridge, Massachusetts, USA
| | - Michaell Huber
- Department of Comprehensive Dentistry, University of Texas Health Science Center at San Antonio, San Antonio, Texas, USA
| | | | | | - Xiaohua D Zhang
- Department of Biostatistics, College of Public Health, University of Kentucky, Lexington, Kentucky, USA
| | - Craig S Miller
- Department of Oral Health Practice, College of Dentistry, University of Kentucky, Lexington, Kentucky, USA
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Kong X, Yu J, Zhu Z, Wang C, Zhang R, Qi J, Wang Y, Wang X, Pan S, Liu L, Feng R. Causal associations of histidine and 12 site-specific cancers: a bidirectional Mendelian randomization study. Mol Genet Genomics 2023; 298:1331-1341. [PMID: 37498357 DOI: 10.1007/s00438-023-02057-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/17/2022] [Accepted: 07/19/2023] [Indexed: 07/28/2023]
Abstract
An increasing number of studies indicate that cancer patients' histidine (HIS) circulating levels have changed. However, the causality between HIS and cancer is still not well established. Thus, to ascertain the causal link between HIS and cancers, we performed a bidirectional Mendelian randomization (MR) analysis. Summary-level data are derived from publicly available genome-wide association studies (GWAS). The causal effects were mainly estimated using the inverse-variance weighted method (IVW). The weighted-median (WM) method and MR-Egger regression were conducted as sensitivity analyses. In the forward-MR, we found malignant neoplasm of respiratory system and intrathoracic organs (OR: 1.020; 95% CI: 1.006-1.035; pIVW = 0.007) genetically associated with circulating HIS. And there was no significant genetic correlation between HIS and another 11 site-specific cancers using IVW method. In the reversed-MR, we did not observe the causal relationship between HIS and 12 site-specific cancers. Our findings help clarify that HIS, as a biomarker for malignant neoplasms of respiratory system and intrathoracic organs, is causal rather than a secondary biomarker of the cancerous progression. The mechanism between histidine and cancer progression deserves further investigation.
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Affiliation(s)
- Xiangju Kong
- Department of Gynaecology, First Affiliated Hospital of Harbin Medical University, Harbin, People's Republic of China
| | - Jiaying Yu
- Department of Nutrition and Food Hygiene, Public Health College, Harbin Medical University, Nan Gang District, 157 Baojian Road, Harbin, 150086, People's Republic of China
| | - Zhuolin Zhu
- Department of Nutrition and Food Hygiene, Public Health College, Harbin Medical University, Nan Gang District, 157 Baojian Road, Harbin, 150086, People's Republic of China
| | - Cheng Wang
- Department of Environmental Hygiene, Public Health College, Harbin Medical University, Harbin, People's Republic of China
| | - Runan Zhang
- Department of Nutrition and Food Hygiene, Public Health College, Harbin Medical University, Nan Gang District, 157 Baojian Road, Harbin, 150086, People's Republic of China
| | - Jiayue Qi
- Department of Nutrition and Food Hygiene, Public Health College, Harbin Medical University, Nan Gang District, 157 Baojian Road, Harbin, 150086, People's Republic of China
| | - Yiran Wang
- Department of Nutrition and Food Hygiene, Public Health College, Harbin Medical University, Nan Gang District, 157 Baojian Road, Harbin, 150086, People's Republic of China
| | - Xiaoxin Wang
- Department of Nutrition and Food Hygiene, Public Health College, Harbin Medical University, Nan Gang District, 157 Baojian Road, Harbin, 150086, People's Republic of China
| | - Sijia Pan
- Department of Nutrition and Food Hygiene, Public Health College, Harbin Medical University, Nan Gang District, 157 Baojian Road, Harbin, 150086, People's Republic of China
| | - Liyan Liu
- Department of Nutrition and Food Hygiene, Public Health College, Harbin Medical University, Nan Gang District, 157 Baojian Road, Harbin, 150086, People's Republic of China.
| | - Rennan Feng
- Department of Nutrition and Food Hygiene, Public Health College, Harbin Medical University, Nan Gang District, 157 Baojian Road, Harbin, 150086, People's Republic of China.
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Bel'skaya LV, Sarf EA, Loginova AI, Vyushkov DM, Choi ED. Potential Diagnostic Value of Salivary Tumor Markers in Breast, Lung and Ovarian Cancer: A Preliminary Study. Curr Issues Mol Biol 2023; 45:5084-5098. [PMID: 37367072 DOI: 10.3390/cimb45060323] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/21/2023] [Revised: 06/04/2023] [Accepted: 06/09/2023] [Indexed: 06/28/2023] Open
Abstract
The aim of the study was to determine the content of tumor markers for breast, lung and ovarian cancer in saliva, as well as for benign diseases of the corresponding organs and in the control group, and to evaluate their diagnostic significance. Strictly before the start of treatment, saliva samples were obtained and the concentrations of tumor markers (AFP, NSE, HE4, CA15-3, CA72-4, CA125 and CEA) were determined using an enzyme immunoassay (ELISA). CA125 and HE4 were simultaneously determined to be in the blood serum of patients with ovarian cancer. The concentrations of salivary CEA, NSE, CA15-3, CA72-4 and CA125 of the control group were significantly lower than in oncological diseases; however, these tumor markers also increased in saliva with benign diseases. The content of tumor markers depends on the stage of cancer, and the presence of lymph node metastasis; however, the identified patterns are statistically unreliable. The determination of HE4 and AFP in saliva was not informative. In general, the area of potential use of tumor markers in saliva is extremely narrow. Thus, CEA may be diagnostic for breast and lung cancer, but not for ovarian cancer. CA72-4 is most informative for ovarian mucinous carcinoma. None of the markers showed significant differences between malignant and non-malignant pathologies.
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Affiliation(s)
- Lyudmila V Bel'skaya
- Biochemistry Research Laboratory, Omsk State Pedagogical University, 14, Tukhachevsky Str., 644099 Omsk, Russia
- Department of Biochemistry, Omsk State Medical University, 12, Lenina Str., 644099 Omsk, Russia
| | - Elena A Sarf
- Biochemistry Research Laboratory, Omsk State Pedagogical University, 14, Tukhachevsky Str., 644099 Omsk, Russia
| | - Alexandra I Loginova
- Clinical Oncology Dispensary, 9/1, Zavertyayeva Str., 644013 Omsk, Russia
- Department of Oncology, Omsk State Medical University, 12, Lenina Str., 644099 Omsk, Russia
| | - Dmitry M Vyushkov
- Clinical Oncology Dispensary, 9/1, Zavertyayeva Str., 644013 Omsk, Russia
- Department of Oncology, Omsk State Medical University, 12, Lenina Str., 644099 Omsk, Russia
| | - En Djun Choi
- Clinic Lekar, 14/4, Presnensky Val Str., 107031 Moscow, Russia
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Liu M, He D, Liu Z, Hu C. Disposable solar microcell array-based addressable photoelectrochemical sensor for high-throughput and multiplexed analysis of salivary metabolites. Biosens Bioelectron 2023; 232:115312. [PMID: 37060863 DOI: 10.1016/j.bios.2023.115312] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/30/2023] [Revised: 03/16/2023] [Accepted: 04/08/2023] [Indexed: 04/17/2023]
Abstract
The high-throughput detection of multiple metabolites in saliva by electrochemical sensors is usually a challenge, which however is essential to the comprehensive evaluation of health status or screening of diseases. Here, a light-addressable and paper-based hydrogen peroxide (H2O2) photoelectrochemical (PEC) sensor for the high-throughput detection of multiple salivary metabolites is reported. This sensor has a unique solar microcell array structure with a silver nanowires/fullerene-Congo red (AgNWs/C60-CR) disc working electrode (WE) and a single-walled carbon nanotubes/platinum nanowires (SWCNTs/PtNWs) ring reference/counter electrode (RE/CE) in each microcell. Enzymes of different metabolites are immobilized on different separated microcells of a cover slide over the sensor, from which enzymatically produced H2O2 can react with p-hydroxyphenyl boric acid (4-HPBA) on the WE of the sensor to generate hydroquinone (HQ) for photocurrent responses. Based on this strategy, a disposable PEC sensor of saliva was developed, which allows the multiplexed detection of uric acid (UA), glucose (GLU) and lactate (LA) in diluted human saliva with high sensitivity and selectivity. Moreover, the detection throughput and application field of the sensor can be easily extended by connecting a series of sensors in parallel or varying the enzymes. The present work thus establishes a cost-effective approach to the scalable construction of versatile biosensing platforms with tunable throughput and varied analytes.
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Affiliation(s)
- Min Liu
- College of Chemistry and Chemical Engineering, Hubei University, Wuhan, 430062, China
| | - Danting He
- College of Chemistry and Molecular Sciences, Wuhan University, Wuhan, 430072, China
| | - Zhihong Liu
- College of Chemistry and Chemical Engineering, Hubei University, Wuhan, 430062, China.
| | - Chengguo Hu
- College of Chemistry and Molecular Sciences, Wuhan University, Wuhan, 430072, China.
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Hyvärinen E, Kashyap B, Kullaa AM. Oral Sources of Salivary Metabolites. Metabolites 2023; 13:metabo13040498. [PMID: 37110157 PMCID: PMC10145445 DOI: 10.3390/metabo13040498] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/16/2023] [Revised: 03/10/2023] [Accepted: 03/28/2023] [Indexed: 03/31/2023] Open
Abstract
The oral cavity is very diverse, where saliva plays an important role in maintaining oral health. The metabolism of saliva has been used to investigate oral diseases as well as general diseases, mainly to detect diagnostic biomarkers. There are many sources of salivary metabolites in the mouth. The online English language search and PubMed databases were searched to retrieve relevant studies on oral salivary metabolites. The physiological balance of the mouth is influenced by many factors that are reflected in the salivary metabolite profile. Similarly, the dysbiosis of microbes can alter the salivary metabolite profile, which may express oral inflammation or oral diseases. This narrative review highlights the factors to be considered when examining saliva and its use as a diagnostic biofluid for different diseases. Salivary metabolites, mainly small molecular metabolites may enter the bloodstream and cause illness elsewhere in the body. The importance of salivary metabolites produced in the oral cavity as risk factors for general diseases and their possible relationship to the body’s function are also discussed.
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Khan H, Shah MR, Barek J, Malik MI. Cancer biomarkers and their biosensors: A comprehensive review. Trends Analyt Chem 2022. [DOI: 10.1016/j.trac.2022.116813] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/06/2022]
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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. Metabolites 2022; 12:metabo12090778. [PMID: 36144183 PMCID: PMC9505390 DOI: 10.3390/metabo12090778] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/30/2022] [Revised: 08/12/2022] [Accepted: 08/15/2022] [Indexed: 11/24/2022] Open
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 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.
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«Salivaomics» of Different Molecular Biological Subtypes of Breast Cancer. Curr Issues Mol Biol 2022; 44:3053-3074. [PMID: 35877435 PMCID: PMC9319144 DOI: 10.3390/cimb44070211] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/11/2022] [Revised: 07/01/2022] [Accepted: 07/04/2022] [Indexed: 11/30/2022] Open
Abstract
The aim of the study was to determine the metabolic characteristics of saliva depending on the molecular biological subtype of breast cancer, as well as depending on the expression levels of HER2, estrogen receptors (ER), and progesterone receptors (PR). The study included 487 patients with morphologically verified breast cancer and 298 volunteers without breast pathologies. Saliva samples were obtained from all patients strictly before the start of treatment and the values of 42 biochemical indicators were determined. It has been established that the saliva of healthy volunteers and patients with various molecular biological subtypes of breast cancer differs in 12 biochemical indicators: concentrations of protein, urea, nitric oxide, malondialdehyde, total amino acid content, and activity of lactate dehydrogenase, alkaline phosphatase, gamma-glutamyltransferase, catalase, amylase, superoxide dismutase, and peroxidases. The saliva composition of patients with basal-like breast cancer differs from other subtypes in terms of the maximum number of indicators. Changes in biochemical indicators indicated an increase in the processes of lipid peroxidation and endogenous intoxication and a weakening of antioxidant protection, which correlates with the severity of the disease and the least favorable prognosis for this subtype of breast cancer. An analysis was made of the individual contribution of the expression level of HER2, estrogen, and progesterone receptors to changes in the biochemical composition of saliva. The HER2 (−)/HER2 (+) group, which should be considered as a single group, as well as ER-positive breast cancer, differ statistically significantly from the control group. For ER/PR-positive breast cancer, a more favorable ratio of saliva biochemical indicators was also noted compared to ER/PR-negative breast cancer.
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Koopaie M, Kolahdooz S, Fatahzadeh M, Manifar S. Salivary biomarkers in breast cancer diagnosis: A systematic review and diagnostic meta-analysis. Cancer Med 2022; 11:2644-2661. [PMID: 35315584 PMCID: PMC9249990 DOI: 10.1002/cam4.4640] [Citation(s) in RCA: 23] [Impact Index Per Article: 7.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/15/2021] [Revised: 12/25/2021] [Accepted: 01/02/2022] [Indexed: 12/19/2022] Open
Abstract
BACKGROUND Salivary diagnostics and their utility as a nonaggressive approach for breast cancer diagnosis have been extensively studied in recent years. This meta-analysis assesses the diagnostic value of salivary biomarkers in differentiating between patients with breast cancer and controls. METHODS We conducted a meta-analysis and systematic review of studies related to salivary diagnostics published in PubMed, EMBASE, Scopus, Ovid, Science Direct, Web of Science (WOS), and Google Scholar. The articles were chosen utilizing inclusion and exclusion criteria, as well as assessing their quality. Specificity and sensitivity, along with negative and positive likelihood ratios (NLR and PLR) and diagnostic odds ratio (DOR), were calculated based on random- or fixed-effects model. Area under the curve (AUC) and summary receiver-operating characteristic (SROC) were plotted and evaluated, and Fagan's Nomogram was evaluated for clinical utility. RESULTS Our systematic review and meta-analysis included 14 papers containing 121 study units with 8639 adult subjects (4149 breast cancer patients and 4490 controls without cancer). The pooled specificity and sensitivity were 0.727 (95% CI: 0.713-0.740) and 0.717 (95% CI: 0.703-0.730), respectively. The pooled NLR and PLR were 0.396 (95% CI: 0.364-0.432) and 2.597 (95% CI: 2.389-2.824), respectively. The pooled DOR was 7.837 (95% CI: 6.624-9.277), with the AUC equal to 0.801. The Fagan's nomogram showed post-test probabilities of 28% and 72% for negative and positive outcomes, respectively. We also conducted subgroup analyses to determine specificity, sensitivity, DOR, PLR, and NLR based on the mean age of patients (≤52 or >52 years old), saliva type (stimulated and unstimulated saliva), biomarker measurement method (mass spectrometry [MS] and non-MS measurement methods), sample size (≤55 or >55), biomarker type (proteomics, metabolomics, transcriptomics and proteomics, and reagent-free biophotonic), and nations. CONCLUSION Saliva, as a noninvasive biomarker, has the potential to accurately differentiate breast cancer patients from healthy controls.
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Affiliation(s)
| | | | - Mahnaz Fatahzadeh
- Department of Diagnostic SciencesRutgers School of Dental MedicineNewarkNew JerseyUSA
| | - Soheila Manifar
- Tehran University of Medical SciencesTehranIran
- Cancer Research Center, Cancer Institute of IranTehranIran
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Tango R, Koeda A, Nagamine K, Tokito S, Niwa O, Ishikawa S, Sugimoto M. Development of a highly sensitive Prussian-blue-based enzymatic biosensor for L-carnitine employing the thiol/disulfide exchange reaction. ANAL SCI 2022; 38:963-968. [PMID: 35578012 DOI: 10.1007/s44211-022-00122-6] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/23/2022] [Accepted: 04/23/2022] [Indexed: 11/01/2022]
Abstract
This is the first report of conducting proof-of-concept study for amperometric acetyltransferase-based L-carnitine sensor by employing the thiol/disulfide exchange reaction. The carnitine acetyltransferase (CrAT) catalyzes the reaction between acetyl-CoA and L-carnitine to produce CoA which is difficult to detect directly by electrochemical methods owing to steric hindrance and electrostatic effect of CoA. The thiol/disulfide exchange reaction between CoA and cystamine was mediated in the enzymatic reaction to produce electrochemically detectable low molecular weight of cationic cysteamine. The sensor exhibited high sensitivity and selectivity for L-carnitine in the concentration range 0.28-50 µM with a limit of detection of 0.28 µM. This is a promising strategy for L-carnitine sensing in point-of-care testing applications.
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Affiliation(s)
- Ryota Tango
- Graduate School of Organic Materials Science, Yamagata University, 4-3-16, Jonan, Yonezawa, 992-8510, Yamagata, Japan
| | - Aya Koeda
- Graduate School of Organic Materials Science, Yamagata University, 4-3-16, Jonan, Yonezawa, 992-8510, Yamagata, Japan
| | - Kuniaki Nagamine
- Graduate School of Organic Materials Science, Yamagata University, 4-3-16, Jonan, Yonezawa, 992-8510, Yamagata, Japan.
| | - Shizuo Tokito
- Graduate School of Organic Materials Science, Yamagata University, 4-3-16, Jonan, Yonezawa, 992-8510, Yamagata, Japan
| | - Osamu Niwa
- Saitama Institute of Technology, 1690, Fusaiji, Fukaya, 369-0293, Saitama, Japan
| | - Shigeo Ishikawa
- Department of Dentistry, Oral and Maxillofacial Plastic and Reconstructive Surgery, Faculty of Medicine, Yamagata University, 2-2-2, lida-nishi, Yamagata, 990-9585, Japan
| | - Masahiro Sugimoto
- Research and Development Center for Minimally Invasive Therapies, Institute of Medical Science, Tokyo Medical University, 6-1-1, Shinjuku, Tokyo, 160-0023, Japan
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14
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Bel'skaya LV, Sarf EA, Shalygin SP, Postnova TV, Kosenok VK. Potential Diagnostic Significance of Salivary Copper Determination in Breast Cancer Patients: A Pilot Study. Biol Trace Elem Res 2022; 200:953-960. [PMID: 33837914 DOI: 10.1007/s12011-021-02710-5] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/27/2021] [Accepted: 04/06/2021] [Indexed: 12/14/2022]
Abstract
Determination of the copper content in the saliva of breast cancer patients was carried out to assess the potential diagnostic and prognostic value. The malignant group included 75 breast cancer patients; the benign group included 87 patients with fibroadenomas; and the control group included 20 volunteers without breast pathology. All participants had 1 ml of saliva collected prior to treatment. The determination of copper in saliva was carried out by the stripping voltammetric method. Overall survival was assessed using the Kaplan-Meier method with the presentation of survival curves and the calculation of the significance of differences by Log-rank. The average copper content in the saliva of breast cancer patients is 49.3% higher than in patients with fibroadenomas and 60.4% higher than in volunteers without breast pathologies. Within the group of breast cancer patients, the content of copper in saliva is heterogeneous, which limits the possibilities of using this indicator for diagnostic purposes. The copper content increases when comparing the initial stages and locally widespread (+ 22.4%) and then sharply increases by 3.5 times at the T3-4N0-2M0 stage. For HER2-positive breast cancer, the copper content in saliva is 51.9% higher than for HER2-negative, a similar pattern was observed for luminal A and B breast cancer subtypes. The content of copper in saliva less than 1.14 mg/l is a prognostically unfavorable sign, while the relative risk of dying from breast cancer more than doubles. Thus, the content of copper in saliva can be used in clinical practice for planning treatment tactics.
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Affiliation(s)
- Lyudmila V Bel'skaya
- Biochemistry Research Laboratory, Omsk State Pedagogical University, Omsk, 644043, Russia.
| | - Elena A Sarf
- Biochemistry Research Laboratory, Omsk State Pedagogical University, Omsk, 644043, Russia
| | - Sergey P Shalygin
- Department of Chemistry, Omsk State Medical University, Omsk, 644099, Russia
| | - Tatyana V Postnova
- Department of Chemistry, Omsk State Medical University, Omsk, 644099, Russia
| | - Victor K Kosenok
- Department of Oncology, Omsk State Medical University, Omsk, 644099, Russia
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Trevisan França de Lima L, Müller Bark J, Rasheduzzaman M, Ekanayake Weeramange C, Punyadeera C. Saliva as a matrix for measurement of cancer biomarkers. Cancer Biomark 2022. [DOI: 10.1016/b978-0-12-824302-2.00008-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
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16
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Gawor JP, Wilczak J, Svensson UK, Jank M. Influence of Dietary Supplementation With a Powder Containing A.N. ProDen™ ( Ascophyllum Nodosum) Algae on Dog Saliva Metabolome. Front Vet Sci 2021; 8:681951. [PMID: 34239914 PMCID: PMC8258245 DOI: 10.3389/fvets.2021.681951] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/17/2021] [Accepted: 05/18/2021] [Indexed: 11/13/2022] Open
Abstract
The objective of this placebo-controlled, double-blind, randomized study (designed according to evidence-based medicine standards) was to determine the effect of 30-day administration of powdered brown algae, Ascophyllum nodosum (ProDen PlaqueOff, SwedenCare AB, Sweden), on saliva metabolomes in dogs. Sixty client-owned dogs underwent professional dental cleaning and were randomly subdivided into two groups receiving daily powdered brown algae A. nodosum, or a placebo (microcrystalline cellulose in powder), adjusted to their bodyweight. After a comprehensive oral health assessment and professional dental cleaning, which were both performed under general anesthesia, clinical assessments for gingivitis, plaque, and calculus were conducted. Saliva samples were collected at Day 0 and Day 30 of supplementation. Whole saliva is a mixed fluid that is derived predominantly from the major salivary glands but it also contains numerous other constituents. Additionally, its composition varies on whether salivary secretion is basal or stimulated. Authors put efforts to avoid contamination of saliva by other constituents and character of saliva was basal. Quadrupole time-of-flight (QTOF) mass spectrometer was used to conduct analysis of the saliva samples. Metabolomic analyses identified clear changes after 30 days of supplementation, and the direction of these changes was completely different than in dogs that received a placebo treatment during the same period. The positive clinical effect of 30 days of A. nodosum supplementation on oral health status in dogs described in previous publication combined with the absence of some metabolites in the saliva of dogs on day 30 of supplementation suggest that brown algae inhibit or turn off some pathways that could enhance plaque or calculus development. The exact mechanism of A. nodosum is still unclear and warrants further study.
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Affiliation(s)
| | - Jacek Wilczak
- Institute of Veterinary Medicine, Department of Physiological Sciences, Warsaw University of Life Sciences, Warsaw, Poland
| | | | - Michal Jank
- Institute of Veterinary Medicine, Department of Pre-Clinical Sciences, Warsaw University of Life Sciences, Warsaw, Poland
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17
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Toan NK, Ahn SG. Aging-Related Metabolic Dysfunction in the Salivary Gland: A Review of the Literature. Int J Mol Sci 2021; 22:5835. [PMID: 34072470 PMCID: PMC8198609 DOI: 10.3390/ijms22115835] [Citation(s) in RCA: 40] [Impact Index Per Article: 10.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/18/2021] [Revised: 05/27/2021] [Accepted: 05/27/2021] [Indexed: 12/13/2022] Open
Abstract
Aging-related salivary dysfunction commonly induces the poor oral health, including decreased saliva flow and dental caries. Although the clinical significance of the salivary glands is well-known, the complex metabolic pathways contributing to the aging-dysfunction process are only beginning to be uncovered. Here, we provide a comprehensive overview of the metabolic changes in aging-mediated salivary gland dysfunction as a key aspect of oral physiology. Several metabolic neuropeptides or hormones are involved in causing or contributing to salivary gland dysfunction, including hyposalivation and age-related diseases. Thus, aging-related metabolism holds promise for early diagnosis, increased choice of therapy and the identification of new metabolic pathways that could potentially be targeted in salivary gland dysfunction.
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Affiliation(s)
| | - Sang-Gun Ahn
- Department of Pathology, School of Dentistry, Chosun University, Gwangju 61452, Korea;
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Abstract
Oral cancer is a major public health problem, and there is an increasing trend
for oral cancer to affect young men and women. Public awareness is poor, and
many patients present with late-stage disease, contributing to high mortality.
Oral cancer is often preceded by a clinical premalignant phase accessible to
visual inspection, and thus there are opportunities for earlier detection and to
reduce morbidity and mortality. Screening asymptomatic individuals by systematic
visual oral examinations to detect the disease has been shown to be feasible. A
positive screen includes both oral cancer and oral potentially malignant
disorders. We review key screening studies undertaken, including 1 randomized
clinical trial. Screening of high-risk groups is cost-effective. Strengths and
weaknesses of oral cancer screening studies are presented to help guide new
research in primary care settings and invigorated by the prospect of using
emerging new technologies that may help to improve discriminatory accuracy of
case detection. Most national organizations, including the US Preventive
Services Task Force, have so far not recommended population-based screening due
a lack of sufficient evidence that screening leads to a reduction in oral cancer
mortality. Where health care resources are high, opportunistic screening in
dental practices is recommended, although the paucity of research in primary
care is alarming. The results of surveys suggest that dentists do perform oral
cancer screenings, but there is only weak evidence that screening in dental
practices leads to downstaging of disease. Where health care resources are low,
the feasibility of using primary health care workers for oral cancer screening
has been tested, and measures indicate good outcomes. Most studies reported in
the literature are based on 1 round of screening, whereas screening should be a
continuous process. This review identifies a huge potential for new research
directions on screening for oral cancer.
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Affiliation(s)
- S. Warnakulasuriya
- King’s College London and WHO
Collaborating Centre for Oral Cancer, London, UK
- S. Warnakulasuriya, Faculty of Dentistry,
Oral & Craniofacial Sciences, King’s College London and WHO Collaborating
Centre for Oral Cancer, London, UK.
| | - A.R. Kerr
- Department of Oral and Maxillofacial
Pathology, Radiology & Medicine, New York University College of Dentistry, New
York, NY, USA
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19
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Majuta SN, DeBastiani A, Li P, Valentine SJ. Combining Field-Enabled Capillary Vibrating Sharp-Edge Spray Ionization with Microflow Liquid Chromatography and Mass Spectrometry to Enhance 'Omics Analyses. JOURNAL OF THE AMERICAN SOCIETY FOR MASS SPECTROMETRY 2021; 32:473-485. [PMID: 33417454 PMCID: PMC8132193 DOI: 10.1021/jasms.0c00376] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 05/06/2023]
Abstract
Field-enabled capillary vibrating sharp-edge spray ionization (cVSSI) has been combined with high-flow liquid chromatography (LC) and mass spectrometry (MS) to establish current ionization capabilities for metabolomics and proteomics investigations. Comparisons are made between experiments employing cVSSI and a heated electrospray ionization probe representing the state-of-the-art in microflow LC-MS methods for 'omics studies. For metabolomics standards, cVSSI is shown to provide an ionization enhancement by factors of 4 ± 2 for both negative and positive ion mode analyses. For chymotryptic peptides, cVSSI is shown to provide an ionization enhancement by factors of 5 ± 2 and 2 ± 1 for negative and positive ion mode analyses, respectively. Slightly broader high-performance liquid chromatography peaks are observed in the cVSSI datasets, and several studies suggest that this results from a slightly decreased post-split flow rate. This may result from partial obstruction of the pulled-tip emitter over time. Such a challenge can be remedied with the use of LC pumps that operate in the 10 to 100 μL·min-1 flow regime. At this early stage, the proof-of-principle studies already show ion signal advantages over state-of-the-art electrospray ionization (ESI) for a wide variety of analytes in both positive and negative ion mode. Overall, this represents a ∼20-50-fold improvement over the first demonstration of LC-MS analyses by voltage-free cVSSI. Separate comparisons of the ion abundances of compounds eluting under identical solvent conditions reveal ionization efficiency differences between cVSSI and ESI and may suggest varied contributions to ionization from different physicochemical properties of the compounds. Future investigations of parameters that could further increase ionization gains in negative and positive ion mode analyses with the use of cVSSI are briefly presented.
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Affiliation(s)
- Sandra N. Majuta
- C. Eugene Bennett Department of Chemistry, West Virginia University, Morgantown WV 26501
| | - Anthony DeBastiani
- C. Eugene Bennett Department of Chemistry, West Virginia University, Morgantown WV 26501
| | - Peng Li
- C. Eugene Bennett Department of Chemistry, West Virginia University, Morgantown WV 26501
| | - Stephen J. Valentine
- C. Eugene Bennett Department of Chemistry, West Virginia University, Morgantown WV 26501
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Baima G, Iaderosa G, Citterio F, Grossi S, Romano F, Berta GN, Buduneli N, Aimetti M. Salivary metabolomics for the diagnosis of periodontal diseases: a systematic review with methodological quality assessment. Metabolomics 2021; 17:1. [PMID: 33387070 DOI: 10.1007/s11306-020-01754-3] [Citation(s) in RCA: 35] [Impact Index Per Article: 8.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/31/2020] [Accepted: 11/30/2020] [Indexed: 02/08/2023]
Abstract
INTRODUCTION Early diagnosis of periodontitis by means of a rapid, accurate and non-invasive method is highly desirable to reduce the individual and epidemiological burden of this largely prevalent disease. OBJECTIVES The aims of the present systematic review were to examine potential salivary metabolic biomarkers and pathways associated to periodontitis, and to assess the accuracy of salivary untargeted metabolomics for the diagnosis of periodontal diseases. METHODS Relevant studies identified from MEDLINE (PubMed), Embase and Scopus databases were systematically examined for analytical protocols, metabolic biomarkers and results from the multivariate analysis (MVA). Pathway analysis was performed using the MetaboAnalyst online software and quality assessment by means of a modified version of the QUADOMICS tool. RESULTS Twelve studies met the inclusion criteria, with sample sizes ranging from 19 to 130 subjects. Compared to periodontally healthy individuals, valine, phenylalanine, isoleucine, tyrosine and butyrate were found upregulated in periodontitis patients in most studies; while lactate, pyruvate and N-acetyl groups were the most significantly expressed in healthy individuals. Metabolic pathways that resulted dysregulated are mainly implicated in inflammation, oxidative stress, immune activation and bacterial energetic metabolism. The findings from MVA revealed that periodontitis is characterized by a specific metabolic signature in saliva, with coefficients of determination ranging from 0.52 to 0.99. CONCLUSIONS This systematic review summarizes candidate metabolic biomarkers and pathways related to periodontitis, which may provide opportunities for the validation of diagnostic or predictive models and the discovery of novel targets for monitoring and treating such a disease (PROSPERO CRD42020188482).
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Affiliation(s)
- Giacomo Baima
- Department of Surgical Sciences, C.I.R. Dental School, University of Turin, Turin, Italy.
| | - Giovanni Iaderosa
- Department of Surgical Sciences, C.I.R. Dental School, University of Turin, Turin, Italy
| | - Filippo Citterio
- Department of Surgical Sciences, C.I.R. Dental School, University of Turin, Turin, Italy
| | - Silvia Grossi
- Department of Surgical Sciences, C.I.R. Dental School, University of Turin, Turin, Italy
| | - Federica Romano
- Department of Surgical Sciences, C.I.R. Dental School, University of Turin, Turin, Italy
| | - Giovanni N Berta
- Department of Clinical and Biological Sciences, University of Turin, Turin, Italy
| | - Nurcan Buduneli
- Department of Periodontology, School of Dentistry, Ege University, İzmir, Turkey
| | - Mario Aimetti
- Department of Surgical Sciences, C.I.R. Dental School, University of Turin, Turin, Italy
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Salivary Stress/Immunological Markers in Crohn's Disease and Ulcerative Colitis. Int J Mol Sci 2020; 21:ijms21228562. [PMID: 33202858 PMCID: PMC7698267 DOI: 10.3390/ijms21228562] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/23/2020] [Revised: 11/09/2020] [Accepted: 11/11/2020] [Indexed: 02/08/2023] Open
Abstract
There is continuous and growing interest in research into new alternatives to standard biomarkers to detect and follow-up disease, reducing physical and psychological stress in patients needing regular and invasive medical examinations for the evaluation of pathologies, including inflammatory bowel diseases (IBD). Saliva is one of the most promising body fluids in the research of new biomarkers, thanks to the large number of molecules it contains. Many molecules present in saliva are often directly correlated to their concentration in the blood but may be affected by the condition of the oral cavity. This means that a careful selection of a specific biomarker is required for each pathology, especially pathologies such as IBD, which may induce inflammation in the oral cavity. Here, we analyze the currently used and the proposed new salivary biomarkers (i.e., calprotectin, cytokines, IgA, cortisol, and oxidative stress markers) for the detection and follow-up of the main subtypes of IBD, known as ulcerative colitis and Crohn's disease.
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Abstract
Introduction: Saliva is an ideal biofluid that can be collected in a noninvasive manner, enabling safe and frequent screening of various diseases. Recent studies have revealed that salivary metabolomics analysis has the potential to detect both oral and systemic cancers. Area covered: We reviewed the technical aspects, as well as applications, of salivary metabolomics for cancer detection. The topics include the effects of preconditioning and the method of sample collection, sample storage, processing, measurement, data analysis, and validation of the results. We also examined the rational relationship between salivary biomarkers and tumors distant from the oral cavity. A strategy to establish standard operating protocols for obtaining reproducible quantification data is also discussed Expert opinion: Salivary metabolomics reflects oral and systematic health status, which potently enables cancer detection. The sensitivity and specificity of each marker and their combinations have been well evaluated, but a validation study is required. Further, the standard operating protocol for each procedure should be established to obtain reproducible data before clinical usage.
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Affiliation(s)
- Masahiro Sugimoto
- Research and Development Centre for Minimally Invasive Therapies, Medical Research Institute, Tokyo Medical University , Tokyo, Japan.,Institute for Advanced Biosciences, Keio University , Yamagata, Japan
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