NANOG is a specific biomarker predicting malignant transformation of proliferative verrucous leukoplakia

Background: Proliferative verrucous leukoplakia (PVL) is a special type of oral leukoplakia with no unified diagnosis criteria. Objective: To evaluate the diagnostic values of NANOG for PVL and explore the associations between NANOG expression and the malignant transformation of PVL. Methods: A total of 112 patients were collected, including 79 cases of PVL (48 cases developed into oral squamous cell carcinoma) and 33 patients diagnosed as conventional oral leukoplakia (COL). The expression of NANOG was detected by immunohistochemical staining. Results: NANOG showed higher expression in 34 cases(70.83%) PVL with malignant transformation, significantly higher than that in PVL without malignant transformation and COL ( P <0.05), and the NANOG expression was correlated with non-homogeneous clinical manifestation and oral epithelial dysplasia ( P <0.001). Receiver operating characteristic (ROC) analysis revealed that it would be used to identify PVL from COL, AUC = 0.674, with sensitivity and specificity of 0.800 and 0.879. Kaplan-Meier plotter data revealed that patients with high NANOG expression had shorter malignant transformation-free survival than those with low expression ( P <0.001). Multivariate COX analysis further confirmed that high NANOG expression was an independent risk factor for malignant transformation of PVL. ROC analysis also revealed that it would be used to predict the malignant transformation of PVL, AUC = 0.806, with sensitivity and specificity of 0.900 and 0.903. The above resultswere also validated in external case cohort. Conclusions: NANOG would be a promising diagnostic and prognostic biomarker for PVL.