Background: 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.Methods: 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.Results: 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).Conclusions: The expressions of podoplanin and ABCG2 in OLP were significantly associated with malignant transformation risk.Impact: Our data suggested that podoplanin and ABCG2 may be used as biomarkers for risk assessment of oral malignant transformation in patients with OLP. Cancer Epidemiol Biomarkers Prev; 19(3); 844-9. ©2010 AACR.

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BackgroundOral leukoplakia (OLK) is a potentially malignant disorder of the oral cavity. However, the underlying mechanism of OLK is still unclear. In this study, we explore possible miRNAs involved in OLK.Methodology/Principal FindingsUsing miRNA microarrays, we profiled miRNA expression in OLK and malignantly transformed OLK (mtOLK) tissue samples. The upregulation of miR-31*, miR-142-5p, miR-33a, miR-1259, miR-146b-5p, miR-886-3p, miR-886-5p, miR-519d, and miR-301a along with the downregulation of miR-572, miR-611, miR-602, miR-675, miR-585, miR-623, miR-637, and miR-1184 in mtOLK were new observations. Fluorescence in situ hybridization (FISH) analyses confirmed that miR-31* is highly expressed in mtOLK. There was a significant difference between the FISH score (p<0.05) in patients with or without recurrent/newly formed OLK. Functional analyses demonstrated that a miR-31* inhibitor decreased apoptosis in the Leuk-1, which is an immortalized oral epithelial cell line spontaneously derived from an oral leukoplakia lesion. miR-31* regulated apoptosis, cell proliferation, migration, and invasion in the HOIEC, which is a HPV E6/E7-immortalized oral epithelial cell line. Furthermore, miR-31* modulated the biological functions of apoptosis, cell proliferation, cell cycle, migration, and invasion in the oral squamous cell carcinoma cell line, Cal-27. Using bioinformatic analyses and dual luciferase reporter assays, we determined that the 3′ untranslated region of fibroblast growth factor 3 (FGF3) is the target of miR-31*. Expression of FGF3 was downregulated or upregulated in the presence of a miR-31* mimic or inhibitor, respectively.Conclusions/SignificanceUpregulation of miR-31* is negatively associated with recurrent/newly formed OLK. MiR-31* may exert similar but distinguishable effects on biological function in oral cells with different malignant potential. FGF3 is the target of miR-31*. miR-31* may play an important role during OLK progression through regulating FGF3. MiRNA* strands may also have prominent roles in oral carcinogenesis.