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Objectives: This study aimed at investigating the molecular mechanism underlying PKM2-mediated cancer invasion., Materials & Methods: To optimize the investigation of PKM2-specific effects, we used two immortalized oral cell lines. The two cell lines drastically differed in PKM2 expression level, particularly in the level of nuclear PKM2, and subsequently in glucose metabolism and tumorigenicity., Results: Knockdown of PKM2 reduced not only the glucose metabolism but also the invasive activity by curtailing the expressions of matrix metalloproteinases (MMP): PKM2 could modulate MMP-9 expression by regulating ETS-1 inside the nucleus. These results were further confirmed in an oral squamous cell carcinoma (OSCC) cell line. In correspondence with in vitro findings, clinicopathological data from OSCC patients indicated strong association between PKM2 expression and poor survival rate. Additionally, upon analysis of public database, significant positive correlation was found between PKM2 and ETS-1 in OSCC., Conclusion: Collectively, this study unveiled the molecular mechanism underlying PKM2-mediated cancer invasion, thereby providing novel targets for therapeutics development against invasive OSCC., Competing Interests: The authors have declared that no competing interests exist.

Objectives: Ameloblastomas are the most common odontogenic epithelial tumors with high recurrence rate. The aim of this study was to identify apoptosis-related genes with recurrence of ameloblastomas and to evaluate its feasibility as a prognostic marker and as a target molecule preventing from recurrence., Materials and Methods: Public microarray data were analyzed. To evaluate their expression in ameloblastoma patients, immunohistochemical staining was performed in 89 human ameloblastoma tissues. Quantitative PCR was performed by use of ameloblastoma cell line (AM-1). Fluorescence activated cell sorting analysis and western blotting were conducted following transfection with siRNA. Further, AM-1 cells were implanted in the renal subcapsular layer of immunodeficient mice., Results: Microarray data analysis revealed that osteoprotegerin (OPG) and B-cell lymphoma 2 (Bcl-2) were the two most upregulated genes in ameloblastoma. Only Bcl-2 expression was significantly (p = 0.020) associated with recurrence in conservative treatment group (n = 17) among 89 patients. Silencing of Bcl-2 increased apoptosis in AM-1 cells in vitro and inhibited tumor nodule formation of AM-1 cells in vivo., Conclusion: These results suggest that Bcl-2 expression is a useful biomarker to predict recurrence of ameloblastomas, and as a therapeutic target molecule to prevent recurrence of ameloblastoma., (© 2019 The Authors Oral Diseases Published by John Wiley & Sons Ltd.)

Purpose: Adenoid cystic carcinoma (ACC) is a high-grade malignant tumor of the salivary glands, clinically characterized by multiple recurrences and late distant metastasis. Biological markers for assessing the prognosis of ACC have remained elusive. The purpose of this study was to investigate whether the protein expressions of ataxia telangiectasia mutated (ATM), p53, and ATM-mediated phosphorylated p53 are related to patient survival in ACC., Materials and Methods: In this study, 48 surgical samples were used to assess the expressions of ATM and its downstream target p53. Fisher's exact test and Kaplan-Meier analysis were conducted to evaluate the role of ATM, p53, and phospho-p53 (S15) protein expressions in predicting patient survival and distant metastasis., Results: Myb expression was positive in 85.4% of ACCs, but did not reflect patient survival rate. In contrast, low expression of ATM in cancer cells was significantly correlated with poor survival rate (p=0.037). Moreover, under positive p53 expression, low expression of ATM was highly predictive of poor survival in ACC (p=0.017)., Conclusion: These data indicate that combined assessment of ATM and p53 expression can serve as a useful prognostic marker for assessing survival rate in patients with ACC of the salivary glands., Competing Interests: The authors have no financial conflicts of interest., (© Copyright: Yonsei University College of Medicine 2018.)

Objective: Squamous cell carcinomas (SCC) are the most common malignancies in the oral mucosa; these carcinomas have been preceded by potentially malignant oral disorders (PMODs), mostly oral leukoplakia (OL). No specific biomarker has been widely accepted for predicting the risk of malignant transformation of PMODs. The aim of this study was to develop an accurate prediction model for the malignant transformation of OL using clinical variables and candidate biomarkers., Materials and Methods: To achieve this goal, 10 candidate biomarkers that had previously been reported as useful molecules were investigated: P53, Ki-67, P16, β-catenin, c-jun, c-met, insulin like growth factor II mRNA-binding protein (IMP-3), cyclooxygenase (COX-2), podoplanin (PDPN) and carbonic anhydrase 9 (CA9). For this study, malignant transformed (n=22, median interval of malignant conversion: 3.3years) and untransformed (n=138) OL specimens with median follow-up period of 11.3years (range: 4.6-23.2years) were immunohistochemically stained., Results: Using univariate Cox regression analysis, all biomarkers were proven to be significant for predicting malignant transformation in OL. To reach the highest prediction accuracy, the repeated simulation was performed, revealing that the combination of P53 and CA9 with the clinical factors including age and degree of dysplasia achieved the highest prediction accuracy. We constructed a nomogram with the identified prognostic factors for predicting the 5-, 10-, and 15-year progression free survival of OL., Conclusions: The proposed nomogram may be useful for the accurate and individual prediction of the transformation to SCC in OL patients and may help clinicians offer appropriate treatments and follow up., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Background: Oral submucous fibrosis (OSF) is a chronic progressive disease of the oral cavity that is considered a common potentially malignant disorder in South Asia. Areca nut chewing is the main etiological factor, but its carcinogenic mechanism has yet to be proven. The purpose of this study was to identify the useful biomarkers in predicting high-risk patients with OSF., Methods: Thirty-six cases of OSF and six cases of normal oral mucosa (NOM) were used for this study. Immunohistochemical staining was performed for Ki67, cyclin D1, p16, p53, β-catenin, c-Jun, c-Met, and insulin-like growth factor II mRNA-binding protein 3 (IMP3). The expression patterns of NOM served as guidelines for the scoring system., Results: The expression of Ki67, cyclin D1, c-Met, IMP3, and β-catenin showed a significant difference between OSF and NOM samples. The combined biomarkers of Ki67 and p16 showed significantly different expression between the transformation and non-transformation groups. With discriminant analysis, we proposed a noble formula and cutoff value for predicting high-risk patients with OSF., Conclusion: The notable biomarkers in our present study were Ki67 and p16 showing significantly different expression levels between the transformation and non-transformation groups. With the identification of high-risk patients with OSF, we can expect to develop more intensive treatment modalities, leading to the reduction in cancer transformation rate from OSF., (© 2016 The Authors. Journal of Oral Pathology & Medicine Published by John Wiley & Sons Ltd.)