MicroRNA-375 as a biomarker for malignant transformation in oral lesions

Abstract

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.