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

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...

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Main Authors: Su-Han Jin, Jian-Guo Zhou, Xiao-Yan Guan, Guo-Hui Bai, Jian-Guo Liu, Liang-Wen Chen
Format: Article
Language:English
Published: Frontiers Media S.A. 2020-12-01
Series:Frontiers in Genetics
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fgene.2020.577585/full
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author Su-Han Jin
Jian-Guo Zhou
Xiao-Yan Guan
Guo-Hui Bai
Guo-Hui Bai
Jian-Guo Liu
Jian-Guo Liu
Liang-Wen Chen
author_facet Su-Han Jin
Jian-Guo Zhou
Xiao-Yan Guan
Guo-Hui Bai
Guo-Hui Bai
Jian-Guo Liu
Jian-Guo Liu
Liang-Wen Chen
author_sort Su-Han Jin
collection DOAJ
description 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.
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spelling doaj.art-169aa39858be463aad84390aeafdaa392022-12-21T22:55:23ZengFrontiers Media S.A.Frontiers in Genetics1664-80212020-12-011110.3389/fgene.2020.577585577585Development of an miRNA-Array-Based Diagnostic Signature for PeriodontitisSu-Han Jin0Jian-Guo Zhou1Xiao-Yan Guan2Guo-Hui Bai3Guo-Hui Bai4Jian-Guo Liu5Jian-Guo Liu6Liang-Wen Chen7Department of Orthodontics, Affiliated Stomatological Hospital of Zunyi Medical University, Zunyi, ChinaDepartment of Oncology, Affiliated Hospital of Zunyi Medical University, Zunyi, ChinaDepartment of Orthodontics, Affiliated Stomatological Hospital of Zunyi Medical University, Zunyi, ChinaSchool of Stomatology, Zunyi Medical University, Zunyi, ChinaSpecial Key Laboratory of Oral Diseases Research, Higher Education Institution, Zunyi, ChinaSchool of Stomatology, Zunyi Medical University, Zunyi, ChinaSpecial Key Laboratory of Oral Diseases Research, Higher Education Institution, Zunyi, ChinaHubei-MOST KLOS & KLOBM, Department of Oral Implantology, School and Hospital of Stomatology, Wuhan University, Wuhan, ChinaPeriodontitis 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.https://www.frontiersin.org/articles/10.3389/fgene.2020.577585/fullperiodontitismiRNAdiagnostic signatureLASSO methodROC curve
spellingShingle Su-Han Jin
Jian-Guo Zhou
Xiao-Yan Guan
Guo-Hui Bai
Guo-Hui Bai
Jian-Guo Liu
Jian-Guo Liu
Liang-Wen Chen
Development of an miRNA-Array-Based Diagnostic Signature for Periodontitis
Frontiers in Genetics
periodontitis
miRNA
diagnostic signature
LASSO method
ROC curve
title Development of an miRNA-Array-Based Diagnostic Signature for Periodontitis
title_full Development of an miRNA-Array-Based Diagnostic Signature for Periodontitis
title_fullStr Development of an miRNA-Array-Based Diagnostic Signature for Periodontitis
title_full_unstemmed Development of an miRNA-Array-Based Diagnostic Signature for Periodontitis
title_short Development of an miRNA-Array-Based Diagnostic Signature for Periodontitis
title_sort development of an mirna array based diagnostic signature for periodontitis
topic periodontitis
miRNA
diagnostic signature
LASSO method
ROC curve
url https://www.frontiersin.org/articles/10.3389/fgene.2020.577585/full
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