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Comprehensive Analysis of Differentially Expressed Genes in Clinically Diagnosed Irreversible Pulpitis by Multiplatform Data Integration Using a Robust Rank Aggregation Approach

  • Liu Liu
    Affiliations
    State Key Laboratory of Oral Diseases and National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, China

    Department of Conservative Dentistry and Endodontics, West China Hospital of Stomatology, Sichuan University, Chengdu, China
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  • Tianyi Wang
    Affiliations
    State Key Laboratory of Oral Diseases and National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, China
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  • Dingming Huang
    Affiliations
    State Key Laboratory of Oral Diseases and National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, China

    Department of Conservative Dentistry and Endodontics, West China Hospital of Stomatology, Sichuan University, Chengdu, China
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  • Dongzhe Song
    Correspondence
    Address requests for reprints to Dr Dongzhe Song, West China Hospital of Stomatology, 14# Third Section, Renmin Nan Road, 610041 Chengdu, China.
    Affiliations
    State Key Laboratory of Oral Diseases and National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, China

    Department of Conservative Dentistry and Endodontics, West China Hospital of Stomatology, Sichuan University, Chengdu, China
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      Abstract

      Introduction

      Molecular diagnosis may overcome the limitations of clinical and histologic diagnosis in pulpitis, thereby benefiting many treatment techniques, such as vital pulp therapies. In this study, integrated microarray data on pulpitis were used to obtain a list of normalized differentially expressed (DE) genes for analyzing the molecular mechanisms underlying pulpitis and identifying potential diagnostic biomarkers.

      Methods

      A systematic search of public microarray and sequencing databases was performed to obtain expression data of pulpitis. Robust rank aggregation (RRA) was used to obtain DE gene lists (RRA_DEmRNAs and RRA_DElncRNAs) between inflamed pulp and normal samples. DE genes were evaluated by functional enrichment analyses, correlation analyses for inflammation-related RRA_DEmRNAs, and protein-protein interaction and competing endogenous RNA network construction. Quantitative real-time polymerase chain reaction validation was applied in snap-frozen pulp tissues.

      Results

      Using the GSE77459 and GSE92681 data sets, 280 RRA_DEmRNAs and 90 RRA_DElncRNAs were identified. RRA_DEmRNAs were significantly enriched in inflammation-related biological processes and osteoclast differentiation and tumor necrosis factor, chemokine, and B-cell receptor signaling pathways. The molecular complex detection and cytoHubba methods identified 2 clusters and 10 hub genes in the protein-protein interaction network. The competing endogenous RNA network was composed of 2 long noncoding RNAs (ADAMTS9-AS2 and LINC00290), 2 microRNAs (hsa-miR-30a-5p and hsa-miR-128-3p), and 3 messenger RNAs (ABCA1, FBLN5, and SOCS3). The expression between most top inflammation-related RRA_DEmRNAs in pulpitis showed positive correlations. Quantitative real-time polymerase chain reacation validated the expression trends of selected genes, including ITGAX, TREM1, CD86, FCGR2A, ADAMTS9-AS2, LINC00290, hsa-miR-30a-5p, hsa-miR-128-3p, RASGRP3, IL3RA, CCDC178, CRISPLD1, LINC01857, AC007991.2, ARHGEF26-AS1, and AL021408.1.

      Conclusions

      The identified biomarkers provide insight into the pathology and may aid in the molecular diagnosis of pulpitis.

      Key Words

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