【摘 要】
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Objective Oral leukoplakia (OL) is the most common premalignant lesion in the site of oral cavity.However, only a small proportion of OLs progress to oral squamous cell carcinoma (OSCC).For early iden
【机 构】
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Department of Oral and Maxillofacial Surgery, Ninth People's Hospital, School of Stomatology,Shangh
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Objective Oral leukoplakia (OL) is the most common premalignant lesion in the site of oral cavity.However, only a small proportion of OLs progress to oral squamous cell carcinoma (OSCC).For early identification of high risk OLs, we investigated the role of the transcriptional repressor, enhancer of Zeste homolog 2 (EZH2), in oral carcinogenesis and the clinical implication of EZH2 as a biornarker for malignant transformation.Materials and Methods Leuk-1 cells were treated with anti-EZH2 siRNA to reduce EZH2 expression and measured for cell cycle distribution, anchorage dependent /independent growth and invasion.Immunohistochemistry was used to measure EZH2 protein levels in OLs of 81 patients.EZH2 protein levels were associated with pathological parameters and clinical outcomes.Results EZH2 inhibition in Leuk-1 cells decreased Leuk-1s invasion capability (P<.01) and anchorage dependent/ independent growth (P<.01),down-regulated cyclin-D1, up-regulated p15INK4B, and increased G1 phase.High expression of EZH2 in OLs was strongly associated with dysplastic histology (P<.0001) and OSCC development (P<.0001by Log-rank test).In the multivariate analysis, EZH2 level is the independent factor for OSCC development (P<.0001).At three years after the tissue examination, none of the 16 patients with EZH2 negative OL developed OSCC whereas 3(11.5%) of the 26 patients with moderate EZH2 expression and 30(76.92%) of the 39 patients with high EZH2 expression developed OSCC (P<.0001).Conclusion The results support the role of EZH2 in oral cancer malignant transformation and suggest that EZH2 may serve as a biomarker to predict OSCC risk and potential target in OSCC prevention.
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