Harrandah Amani M, Fitzpatrick Sarah G, Smith Molly H, Wang Dunrui, Cohen Donald M, Chan Edward K L
Department of Oral Biology, University of Florida College of Dentistry, Gainesville, FL, USA.
Department of Oral and Maxillofacial Diagnostic Sciences, University of Florida College of Dentistry, Gainesville, FL, USA.
Oral Surg Oral Med Oral Pathol Oral Radiol. 2016 Dec;122(6):743-752.e1. doi: 10.1016/j.oooo.2016.07.022. Epub 2016 Aug 6.
Malignant transformation of oral premalignant lesions is the key process in the progression to oral squamous cell carcinoma (OSCC). Previously, we identified miR-7 and miR-21 as candidate oncogenes and miR-375 and miR-494 as candidate tumor suppressors in OSCC. We aim to evaluate these microRNAs as biomarkers of malignant transformation in oral premalignant lesions.
Formalin-fixed, paraffin-embedded samples from progressive premalignant lesions and paired sequential OSCC tumors at the same site were obtained from same patients (n = 31). Total RNA was extracted and analyzed for microRNA levels using real-time polymerase chain reaction.
MiR-375 expression in progressive lesions was clearly lower than in nonprogressive control lesions (average eightfold difference, P = .0004). Furthermore, the expression of miR-375 decreased significantly after the progression from premalignant lesion to OSCC (P < .0001). Receiver operating characteristic curve analysis revealed that miR-375 was able to differentiate between progressive and nonprogressive premalignant lesions (P < .0001).
MiR-375 downregulation in oral premalignant lesions is associated with a higher risk of malignant transformation.
口腔癌前病变的恶性转化是进展为口腔鳞状细胞癌（OSCC）的关键过程。此前，我们已确定miR-7和miR-21为OSCC的候选癌基因，miR-375和miR-494为候选抑癌基因。我们旨在评估这些微小RNA作为口腔癌前病变恶性转化生物标志物的作用。
从同一患者（n = 31）获取福尔马林固定、石蜡包埋的进行性癌前病变样本以及同一部位配对的连续性OSCC肿瘤样本。提取总RNA，使用实时聚合酶链反应分析微小RNA水平。
进行性病变中miR-375的表达明显低于非进行性对照病变（平均相差8倍，P = .0004）。此外，从癌前病变进展为OSCC后，miR-375的表达显著降低（P < .0001）。受试者工作特征曲线分析显示，miR-375能够区分进行性和非进行性癌前病变（P < .0001）。
口腔癌前病变中miR-375的下调与更高的恶性转化风险相关。
