Comprehensive Analysis of Differentially Expressed Genes in Clinically Diagnosed Irreversible Pulpitis by Multiplatform Data Integration Using a Robust Rank Aggregation Approach
Comprehensive Analysis of Differentially Expressed Genes in Clinically Diagnosed Irreversible Pulpitis by Multiplatform Data Integration Using a Robust Rank Aggregation Approach
复制标题
使用稳健的排名聚合方法通过多平台数据集成综合分析临床诊断的不可逆性牙髓炎的差异表达基因
DOI：
10.1016/j.joen.2021.07.007
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发表时间：
2021-08-21
影响因子：
4.2
通讯作者：
Song, Dongzhe
中科院分区：
文献类型：
--
作者：
Liu, Liu;Wang, Tianyi;Song, Dongzhe
简介：分子诊断可以克服临床和组织学诊断的局限性，从而有利于许多治疗技术，如活髓治疗。在这项研究中，集成的微阵列数据牙髓炎被用来获得一个标准化的差异表达（DE）基因的列表，用于分析牙髓炎的分子机制，并确定潜在的诊断生物标志物。方法：系统检索公开的基因芯片和测序数据库，获得牙髓炎相关基因的表达数据。使用鲁棒秩聚合（RRA）获得发炎牙髓和正常样品之间的DE基因列表（RRA_DEmRNAs和RRA_DEIncRNAs）。通过功能富集分析、炎症相关RRA_DEmRNA相关性分析、蛋白质-蛋白质相互作用和竞争性内源性RNA网络构建来评估DE基因。实时定量聚合酶链反应验证应用于速冻牙髓组织。结果：利用GSE 77459和GSE 92681数据集，共鉴定出280个RRA_DEmRNA和90个RRA_DEIncRNA。RRA_DEmRNA在炎症相关的生物学过程和破骨细胞分化以及肿瘤坏死因子、趋化因子和B细胞受体信号通路中显著富集。分子复合物检测和cytoHubba方法在蛋白质-蛋白质相互作用网络中鉴定出2个簇和10个枢纽基因。竞争性内源性RNA网络由2种长非编码RNA（ADAMTS 9-AS 2和LINC 00290）、2种microRNA（hsa-miR-30 a-5 p和hsa-miR-128- 3 p）和3种信使RNA（ABCA 1、FBLN 5和SOCS 3）组成。牙髓炎组织中多数炎症相关基因RRA_DEmRNA的表达呈正相关。定量实时聚合酶链反应验证了选定基因的表达趋势，包括/TGAX、TREM 1、CD 86、FCGR 2A、ADAMTS 9-AS 2、LINC 00290、hsa-miR-30 a-5 p、hsa-miR-128- 3 p、RASGRP 3、IL 3RA、CCDC 178、CRISPLD 1、LINC 01857、AC007991.2、ARHGEF 26-AS 1和AL021408.1。结论：所确定的生物标志物提供了深入了解病理学，并可能有助于牙髓炎的分子诊断。
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_DEIncRNAs) 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_DEIncRNAs 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 /TGAX, 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.