[Show abstract][Hide abstract] ABSTRACT: Oral cancer is the sixth most common human cancer, with a high morbidity rate and an overall 5-year survival rate of less
than 50%. It is often not diagnosed until it has reached an advanced stage. Therefore, an early diagnostic and stratification
strategy is of great importance for oral cancer. In the current study, urine samples of patients with oral squamous cell carcinoma
(OSCC, n = 37), oral leukoplakia (OLK, n = 32) and healthy subjects (n = 34) were analyzed by gas chromatography-mass spectrometry
(GC–MS). Using multivariate statistical analysis, the urinary metabolite profiles of OSCC, OLK and healthy control samples
can be clearly discriminated and a panel of differentially expressed metabolites was obtained. Metabolites, valine and 6-hydroxynicotic
acid, in combination yielded an accuracy of 98.9%, sensitivity of 94.4%, specificity of 91.4%, and positive predictive value
of 91.9% in distinguishing OSCC from the controls. The combination of three differential metabolites, 6-hydroxynicotic acid,
cysteine, and tyrosine, was able to discriminate between OSCC and OLK with an accuracy of 92.7%, sensitivity of 85.0%, specificity
of 89.7%, and positive predictive value of 91.9%. This study demonstrated that the metabolite markers derived from this urinary
metabolite profiling approach may hold promise as a diagnostic tool for early stage OSCC and its differentiation from other
[Show abstract][Hide abstract] ABSTRACT: Oral cancer, one of the six most common human cancers with an overall 5-year survival rate of <50%, is often not diagnosed until it has reached an advanced stage. The aim of the current study is to explore salivary metabolomics as a disease diagnostic and stratification tool for oral cancer and leukoplakia and evaluate the potential of salivary metabolome for detection of oral squamous cell carcinoma (OSCC). Saliva metabolite profiling for a group of 37 OSCC patients, 32 oral leukoplakia (OLK) patients and 34 healthy subjects was performed using ultraperformance liquid chromatography coupled with quadrupole/time-of-flight mass spectrometry in conjunction with multivariate statistical analysis. The OSCC, OLK and healthy control groups demonstrate characteristic salivary metabolic signatures. A panel of five salivary metabolites including γ-aminobutyric acid, phenylalanine, valine, n-eicosanoic acid and lactic acid were selected using OPLS-DA model with S-plot. The predictive power of each of the five salivary metabolites was evaluated by receiver operating characteristic curves for OSCC. Valine, lactic acid and phenylalanine in combination yielded satisfactory accuracy (0.89, 0.97), sensitivity (86.5% and 94.6%), specificity (82.4% and 84.4%) and positive predictive value (81.6% and 87.5%) in distinguishing OSCC from the controls or OLK, respectively. The utility of salivary metabolome diagnostics for oral cancer is successfully demonstrated in this study and these results suggest that metabolomics approach complements the clinical detection of OSCC and stratifies the two types of lesions, leading to an improved disease diagnosis and prognosis.
Full-text · Article · Nov 2011 · International Journal of Cancer
[Show abstract][Hide abstract] ABSTRACT: Oral leukoplakia (OL) is the best-known potentially malignant disorder. A new binary system to grade dysplasia was proposed by WHO, but the biological significance in predicting malignant transformation risk is unknown. The objective of this study is to estimate the rate of malignant transformation in a long-term follow-up cohort, explore the usefulness of the new binary system of grading dysplasia and identify significant risk factors of OL malignant transformation in China.
A total of 218 patients with clinical and histopathologic diagnosis of OL were retrospectively reviewed. They were selected among all archived files at the Department of Oral Mucosal Diseases, Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine. The mean follow-up period was 5.3 years.
Among 218 cases, 39 (17.9%) OL patients developed oral cancer, with a mean duration of 5.2 years. Cox regression analysis revealed that dysplasia was an independent risk factor for OL malignant transformation, but age, gender, lesion site, diet habit, smoking and ethanol intake were not risk factors. High-risk dysplastic OL was associated with a 4.57-fold (95% confidence interval, 2.36-8.84; P < 0.001) increased risk of malignant transformation, compared with low-risk dysplasia. Consistent with this result, high-risk dysplastic OL had significantly higher malignant incidence than low-risk dysplasia, particularly during the first 2-3 years of follow-up, by Kaplan-Meier analysis (Log-rank test, P < 0.001).
The new binary system's function in predicting OL malignant transformation risk was investigated in this survey. The utilization of high-risk dysplasia as a significant indicator for evaluating malignant transformation risk in patients with OL was suggested, which may be helpful to guide treatment selection in clinical practice.
[Show abstract][Hide abstract] ABSTRACT: Oral lichen planus (OLP) is a potentially malignant disorder associated with an increased risk for oral cancer. The purpose of this study was to determine protein expression of podoplanin and ATP-binding cassette, G2 subfamily (ABCG2) in patients with OLP and evaluate their use as biomarkers for OLP malignant transformation risk.
Podoplanin and ABCG2 expressions were determined in samples from 110 patients with untransformed OLP and 9 patients with malignant transformed OLP (mean follow-up of 5.1 years). We compared podoplanin expression, ABCG2 expression, and clinicopathologic parameters between the two groups.
Podoplanin expression was observed in 48 of 110 (43.6%) cases of untransformed OLP and in 8 of 9 (88.9%) cases of transformed OLP. ABCG2 expression was found in 23 of 110 (20.9%) cases of untransformed OLP and in 6 of 9 (66.7%) cases of transformed OLP. Multivariate regression analysis revealed that podoplanin or ABCG2 expression was associated with 17.13-fold [95% confidence interval (95% CI), 1.71-171.22; P = 0.016] or 6.04-fold (95% CI, 1.20-30.36; P = 0.029) increased risk of malignant transformation, respectively. The risk of OLP malignant transformation was considerably higher with coexpression of podoplanin and ABCG2 than without coexpression of podoplanin and ABCG2 (odds ratio, 25.24; 95% CI, 4.48-142.27; P < 0.001).
The expressions of podoplanin and ABCG2 in OLP were significantly associated with malignant transformation risk.
Our data suggested that podoplanin and ABCG2 may be used as biomarkers for risk assessment of oral malignant transformation in patients with OLP.
Preview · Article · Mar 2010 · Cancer Epidemiology Biomarkers & Prevention
[Show abstract][Hide abstract] ABSTRACT: To explore circulation levels of osteopontin (OPN), tumour necrosis factor (TNF)-alpha and transforming growth factor (TGF)-beta1 from patients with oral lichen planus (OLP) for clinical application. A group of 26 subjects with OLP were compared with 26 sex- and age-matched control (NC) subjects. Local lesion tissue was examined for OPN by immunohistochemical analysis. And, serum OPN, proinflammatory TNF-alpha and TGF-beta1 levels were measured by enzyme-linked immunoabsorbent assay. The serum concentrations of OPN and TNF-alpha were significantly higher in OLP patients than the NC group (P < 0.05). Although serum concentrations of TGF-beta1 increased slightly, they were not statistically significant. Erosive-form OLP exhibited significantly elevated TGF-beta1 serum levels, compared with reticular-form OLP. The above results suggest that the production of OPN is associated with the inflammatory process of OLP development, and may serve as a potential disease marker of OLP.
No preview · Article · Feb 2008 · Journal of Oral Pathology and Medicine