MicroRNA-137 promoter methylation is associated with poorer overall survival in patients with squamous cell carcinoma of the head and neck.

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作者:Langevin Scott M, Stone Roslyn A, Bunker Clareann H, Lyons-Weiler Maureen A, LaFramboise William A, Kelly Lori, Seethala Raja R, Grandis Jennifer R, Sobol Robert W, Taioli Emanuela
BACKGROUND: The overall 5-year survival rate of approximately 60% for head and neck cancer patients has remained essentially unchanged over the past 30 years. MicroRNA-137 (miR-137) plays an essential role in cell-cycle control at the G1/S-phase checkpoint. However, the aberrant miR-137 promoter methylation observed in squamous cell carcinoma of the head and neck (SCCHN) suggests a tumor-specific molecular defect that may contribute to disease progression. METHODS: The goal of this study was to assess, in formalin-fixed, paraffin-embedded tumor tissue, the association between miR-137 promoter methylation and survival (both overall and disease free) and with prognostic factors including stage, tumor size, lymph node positivity, tumor grade, and surgical tumor margin positivity. RESULTS: The promoter methylation status of miR-137 was ascertained by methylation-specific polymerase chain reaction and detected in 11 of 67 SCCHN patients (16.4%), with no significant differences according to site (oral cavity, pharynx, larynx). Methylation of the miR-137 promoter was significantly associated with overall survival (hazard ratio, 3.68; 95% confidence interval, 1.01-13.38) but not with disease-free survival or any of the prognostic factors evaluated. CONCLUSIONS: The results of this study indicate that miR-137 is methylated in tumor tissue from pharyngeal and laryngeal squamous cancers, in addition to oral squamous cell carcinoma, and that miR-137 promoter methylation has potential utility as a prognostic marker for SCCHN.

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