Levels of potential oral cancer salivary mRNA biomarkers in oral cancer patients in remission and oral lichen planus patients.

OBJECTIVES: To gather preliminary data concerning the feasibility of using seven salivary mRNAs-IL-8; IL-1ß; dual specificity phosphatase 1 (DUSP1); H3 histone family 3A (H3F3A); ornithin decarboxylase antizyme 1 (OAZ1); S100 calcium-binding protein P (S100P); and spermidine/spermine N1-acetyltransferase 1 (SAT1)-for detecting development of oral squamous cell carcinoma (OSCC) in oral lichen planus (OLP) patients and OSCC patients whose disease was in remission. MATERIALS AND METHODS: Saliva samples were collected from five study groups (25 subjects/group): newly diagnosed OSCC, OSCC-in-remission, disease-active OLP, disease-inactive OLP, and normal controls. The salivary mRNA levels were determined by a pre-amplification RT-qPCR approach with nested gene-specific primers. Mean fold changes between each pair of study groups were analyzed by the Mann-Whitney U test. RESULTS: Salivary levels of OAZ1, S100P, and DUSP1 mRNAs were significantly higher in newly diagnosed OSCC patients, compared to: (1) normal controls (p = 0.003; p = 0.003; and p < 0.001, respectively); (2) OSCC-in-remission (p < 0.001; p = 0.001; and p < 0.001, respectively); (3) disease-active OLP (p < 0.001; p = 0.016; and p < 0.001, respectively); and (4) disease-inactive OLP (p = 0.043; p < 0.001; and p < 0.001, respectively). No significant differences were found in the levels of salivary IL-8, IL-1ß, H3F3A, and SAT1 mRNAs between newly diagnosed OSCC patients and the normal controls (p = 0.093, 0.327, 0.764, and 0.560, respectively). CONCLUSION: Salivary OAZ1, S100P, and DUSP1 mRNAs are candidate biomarkers for detecting OSCC development in OSCC patients in remission and in OLP patients. CLINICAL RELEVANCE: The results of this study serve as the basis for a further large-scale study which may lead to a non-invasive screening method for early detection of OSCC.

Development of transcriptomic biomarker signature in human saliva to detect lung cancer.

Lung cancer is the leading cause of cancer death for both men and women worldwide. Since most of the symptoms found for lung cancer are nonspecific, diagnosis is mostly done at late and progressed stage with the consecutive poor therapy outcome. Effective early detection techniques are sorely needed. The emerging field of salivary diagnostics could provide scientifically credible, easy-to-use, non-invasive and cost-effective detection methods. Recent advances have allowed us to develop discriminatory salivary biomarkers for a variety of diseases from oral to systematic diseases. In this study, salivary transcriptomes of lung cancer patients were profiled and led to the discovery and pre-validation of seven highly discriminatory transcriptomic salivary biomarkers (BRAF, CCNI, EGRF, FGF19, FRS2, GREB1, and LZTS1). The logistic regression model combining five of the mRNA biomarkers (CCNI, EGFR, FGF19, FRS2, and GREB1) could differentiate lung cancer patients from normal control subjects, yielding AUC value of 0.925 with 93.75 % sensitivity and 82.81 % specificity in the pre-validation sample set. These salivary mRNA biomarkers possess the discriminatory power for the detection of lung cancer. This report provides the proof of concept of salivary biomarkers for the non-invasive detection of the systematic disease. These results poised the salivary biomarkers for the initiation of a multi-center validation in a definitive clinical context.

Salivary diagnostics: moving to the next level.

The evolution of salivary diagnostics has reached a new level toward the goal of using saliva as a powerful fluid for early detection and the first line of diagnosis for life-threatening diseases such as cancer, metabolic disorders, infections, and inflammatory diseases. Newly developed tools such as the novel saliva-based POCT and the SKB are helping to realize the goal of making salivary diagnostics available to clinicians worldwide. This is a unique moment where dentistry may be paving a new path for primary healthcare.

Salivary transcriptome biomarkers in oral squamous cell cancer detection.

In all, 350,000 new cases of oral cancer are reported annually worldwide, 35,000 of these occur in the United States. For decades, the 5-year survival rate has remained low at only 60%, which is mainly due to cancer diagnosis at late and progressed stage. Using saliva as a diagnostic medium could be the key for early detection and thus improved survival rates. Among all salivary constituents, the transcriptome has turned out to be a highly promising biomarker source. So far, seven mRNA and two microRNA markers were found to be discriminatory in saliva of oral cancer patients. This review will give an overview on the field of salivary transcriptome research with focus on oral cancer detection as well as the translation of salivary diagnostics into clinical reality.

Salivary biomarkers for periodontal disease diagnostics.

IMPORTANCE OF THE FIELD: Periodontal disease is one of the most prevalent of all diseases. The chronic inflammatory process causes tooth loss and is associated with negative systemic effects. There are still major challenges when it comes to precise diagnosis, prognosis and appropriate disease therapy. The rapidly emerging field of salivary diagnostics could help to overcome these problems. AREAS COVERED IN THIS REVIEW: The article covers the last 20 years of periodontal disease biomarker research and gives an overview of the current status of salivary diagnostic techniques. WHAT THE READER WILL GAIN: The reader will gain insight into the periodontopathic process, associated biomarkers and biomarker detection techniques in the field of saliva-based molecular diagnostics. TAKE HOME MESSAGE: Salivary diagnostics has great potential for the detection of oral and systemic diseases. Periodontal disease diagnostics, therapy and prognosis could benefit from this emerging diagnostic field.

Oral squamous cell carcinoma detection by salivary biomarkers in a Serbian population.

Early detection of oral squamous cell cancer (OSCC) is the key to improve the low 5-year survival rate. Using proteomic and genomic technologies we have previously discovered and validated salivary OSCC markers in American patients. The question arises whether these biomarkers are discriminatory in cohorts of different ethnic background. Six transcriptome (DUSP1, IL8, IL1B, OAZ1, SAT1, and S100P) and three proteome (IL1B, IL8, and M2BP) biomarkers were tested on 18 early and 17 late stage OSCC patients and 51 healthy controls with quantitative PCR and ELISA. Four transcriptome (IL8, IL1B, SAT1, and S100P) and all proteome biomarkers were significantly elevated (p<0.05) in OSCC patients. The combination of markers yielded an AUC of 0.86, 0.85 and 0.88 for OSCC total, T1-T2, and T3-T4, respectively. The sensitivity/specificity for OSCC total was 0.89/0.78, for T1-T2 0.67/0.96, and for T3-T4 0.82/0.84. In conclusion, seven of the nine salivary biomarkers (three proteins and four mRNAs) were validated and performed strongest in late stage cancer. Patient-based salivary diagnostics is a highly promising approach for OSCC detection. This study shows that previously discovered and validated salivary OSCC biomarkers are discriminatory and reproducible in a different ethnic cohort. These findings support the feasibility to implement multi-center, multi-ethnicity clinical trials towards the pivotal validation of salivary biomarkers for OSCC detection.