Development of an miRNA-Array-Based Diagnostic Signature for Periodontitis

Abstract

Periodontitis progression is accompanied by irreversible alveolar bone absorption and leads to tooth loss. Early diagnosis is important for tooth stability and periodontal tissue preservation. However, there is no recognized miRNA diagnostic signature with convincing sensitivity and specificity for periodontitis. In this study, we obtained miRNA array expression profiles of periodontitis from the Gene Expression Omnibus (GEO) database. After screening for differentially expressed miRNAs, the least absolute shrinkage and selection operator (LASSO) method was performed to identify and construct a 17-miRNA-based diagnostic signature (hsa-miR-3917, hsa-mir-4271, hsa-miR-3156, hsa-miR-3141, hsa-miR-1246, hsa-miR-125a-5p, hsa-miR-671-5p, hcmv-mir-UL70, hsa-miR-650, hsa-miR-497-3p, hsa-miR-145-3p, hsa-miR-141-3p, hsa-miR-210-3p, hsa-miR-204-3p, hsa-miR-203a-5p, hsa-miR-99a-3p, and hsa-miR-30a-3p). Periodontal tissue samples with higher risk scores were more likely to show symptoms of periodontitis. Then, the receiver operating characteristic (ROC) curves were used to assess the diagnostic value of the miRNA signature, which indicated that the optimum cutoff value in periodontitis diagnosis was 0.5056 with an area under the ROC curve (AUC) of 0.996, a sensitivity of 97.3%, a specificity of 100.0% in the training cohort; in the testing cohort, the corresponding values were as follows: an AUC of 0.998, a sensitivity of 97.9%, and a specificity of 91.7%. We next evaluated the efficacy of the signature in differentiating disease subtype and affected range. Furthermore, we conducted functional enrichment analysis of the 17 miRNA-targeted mRNAs, including the regulation of mTOR activity and cell autophagy, Th1/Th2 cell balance and immunoregulation, cell apoptosis, and so on. In summary, our study identified and validated a 17-miRNA diagnostic signature with convincing AUC, sensitivity, and specificity for periodontitis.

Cannabinoid control of gingival immune activation in chronically SIV-infected rhesus macaques involves modulation of the indoleamine-2,3-dioxygenase-1 pathway and salivary microbiome

“…Perfect miRNA seed nucleotide matches (miRNA nucleotide positions 2–7) were identified for miR-125a-5p on the 3′ mRNA UTR of DUOX1 (conserved in human, chimp and RM) that had a minimum free energy of −34.6 kcal/mol ( Figure 4 e ). Moreover, miR-125a-5p dysregulation has been confirmed in periodontal disease 52 (blue arrow in Figure 4 b ). Using RT-qPCR, we further confirmed significant downregulation of DUOX1 ( Figure 4 f ) and upregulation of its targeting miR-125a-5p in the gingiva of VEH/SIV RMs ( Figure 4 g ).…”

Autophagy-Related Genes Predict the Progression of Periodontitis Through the ceRNA Network

“…In addition, a 17-miRNA-based diagnostic signature was identified for periodontitis, which included miR-671-5p. 11 A previous study has shown that miR-671-5p played a significant role in inhibiting the characteristics of osteosarcoma cells. 47 In brief, the above three miRNAs may be linked to the onset of periodontitis.…”

“…The absolute value of log 2 FC greater than 1 is commonly used as the screening criterion for differential genes in the literature, whereas periodontitis-related bioinformatics analysis articles frequently choose a lesser value. For instance, Song et al 27 chose 0.58 while Jin et al 11 selected 0.45 as the screening index. Considering that periodontitis is not only a polygenic disease, but also affected by many factors such as microorganisms, smoking, stress, and systemic diseases.…”

“…Recent investigations have revealed critical functions of mRNAs, miRNAs, and lncRNAs in the pathogenesis of periodontitis. 10 , 11 The competing endogenous RNA (ceRNA) hypothesis, suggested by Salmena et al, revealed a new mechanism of interaction between RNAs. 12 For instance, miRNA can lead to gene silencing by binding to the microRNA response elements (MREs) of mRNA, while lncRNA, pseudogenes, and circular RNA can regulate gene expression by competitively sponging miRNA.…”

Early Biomarkers of Periodontitis: New Challenges for a Personalized Medicine Approach

“…miRNAs are implicated in several physiological and pathological mechanisms and play important roles in inflammatory responses and the development of diseases, including cancer and rheumatoid arthritis [ 3 ]. miRNAs can be biomarkers for cancer diagnosis and prognosis, and specific serum miRNAs have been used as diagnostic tools for malignancies, autoimmune diseases, and infectious diseases [ 4 ].…”