Potential of IL12RB2 and TNFRSF8 gene as diagnostic biomarkers of oral lichen planus

Abstract

Purpose: To evaluate the potential of interleukin 12, beta 2 subunit (IL12RB2) and tumor necrosis factor superfamily, member 8 (TNFRSF8) as diagnostic biomarkers of oral lichen planus (OLP) by investigating the expression of IL12RB2 and TNFRSF8 mRNA in formalin-fixed, paraffin-embedded (FFPE) OLP samples and using multiple predictive modeling methods.

Materials & Methods: The mRNA expression of IL12RB2 and TNFRSF8 gene in OLP FFPE samples (OLP group, n = 38) was investigated with qRT-PCR analysis and compared to the mRNA expression of these genes in cases of chronic non-specific mucositis (non-OLP group, n = 25) and normal mucosa (normal group, n = 18). Predictive modeling of the expression of IL12RB2 and TNFRSF8 genes was constructed using support vector machine (SVM), random forest (RF), linear discriminant analysis (LDA), neural network (NN), and naive Bayes (NB) methods.

Results: Expression of IL12RB2 mRNA was significantly higher in both the OLP and non-OLP group compared to the normal group (3.78 ± 1.67, 6.86 ± 1.67 and 1.97 ± 1.12 for the OLP, non-OLP, and normal groups, respectively, p < 0.001), and the OLP-group had a significantly lower expression of IL12RB2 compared with the non-OLP group (p < 0.001). TNFRSF8 gene expression in both the OLP and non-OLP groups was also significantly higher than that of the normal group (7.46 ± 1.51, 6.99 ± 1.96 and 2.90 ± 1.61 for the OLP, non-OLP, and normal groups, p < 0.001). However, there was no significant difference in TNFRSF8 expression between the OLP and non-OLP groups. (p = 0.311) The expression ratio of IL12RB2/TNFRSF8 in OLP group was significantly lower than that of the normal group (OLP:normal = 0.52 ± 0.23:0.74 ± 0.39, p < 0.05), and non-OLP group (OLP:non-OLP = 0.52 ± 0.23:1.07±0.38, p < 0.001). The expression ratio of IL12RB2/TNFRSF8 in the non-OLP group was significantly higher than that of the normal group (p < 0.01). The predictive modeling showed that the values of the area under the receiver operating characteristic (ROC) curves ranged from 0.86 to 0.91 except that of NN (0.83). RF was the most sensitive method (0.90), and NB had the highest specificity (0.85). All methods had an accuracy greater than 0.75.

Conclusions: IL12RB2 can be used as a biomarker for differentiating OLP from chronic non-specific mucositis, and IL12RB2 and TNFRSF8 gene expression can be a useful diagnostic tool for OLP.