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广泛侵袭性牙周炎的基因表达谱:基于基因网络的微阵列分析

Gene-Expression Profiles in Generalized Aggressive Periodontitis: A Gene Network-Based Microarray Analysis.

作者信息

Guzeldemir-Akcakanat Esra, Sunnetci-Akkoyunlu Deniz, Orucguney Begum, Cine Naci, Kan Bahadır, Yılmaz Elif Büsra, Gümüşlü Esen, Savli Hakan

机构信息

Department of Periodontology, Faculty of Dentistry, Kocaeli University, Kocaeli, Turkey.

Department of Medical Genetics, Faculty of Medicine, Kocaeli University.

出版信息

J Periodontol. 2016 Jan;87(1):58-65. doi: 10.1902/jop.2015.150175. Epub 2015 Jul 2.

Abstract

BACKGROUND

In this study, molecular biomarkers that play a role in the development of generalized aggressive periodontitis (GAgP) are investigated using gingival tissue samples through omics-based whole-genome transcriptomics while using healthy individuals as background controls.

METHODS

Gingival tissue biopsies from 23 patients with GAgP and 25 healthy individuals were analyzed using gene-expression microarrays with network and pathway analyses to identify gene-expression patterns. To substantiate the results of the microarray studies, real-time quantitative reverse transcription-polymerase chain reaction (qRT-PCR) was performed to assess the messenger RNA (mRNA) expression of MZB1 and DSC1. The microarrays and qRT-PCR resulted in similar gene-expression changes, confirming the reliability of the microarray results at the mRNA level.

RESULTS

As a result of the gene-expression microarray studies, four significant gene networks were identified. The most upregulated genes were found as MZB1, TNFRSF17, PNOC, FCRL5, LAX1, BMS1P20, IGLL5, MMP7, SPAG4, and MEI1; the most downregulated genes were found as LOR, LAMB4, AADACL2, MAPT, ARG1, NPR3, AADAC, DSC1, LRRC4, and CHP2.

CONCLUSIONS

Functions of the identified genes that were involved in gene networks were cellular development, cell growth and proliferation, cellular movement, cell-cell signaling and interaction, humoral immune response, protein synthesis, cell death and survival, cell population and organization, organismal injury and abnormalities, molecular transport, and small-molecule biochemistry. The data suggest new networks that have important functions as humoral immune response and organismal injury/abnormalities. Future analyses may facilitate proteomic profiling analyses to identify gene-expression patterns related to clinical outcome.

摘要

背景

在本研究中,以健康个体作为背景对照,通过基于组学的全基因组转录组学技术,利用牙龈组织样本研究在广泛侵袭性牙周炎(GAgP)发展过程中发挥作用的分子生物标志物。

方法

使用基因表达微阵列对23例GAgP患者和25例健康个体的牙龈组织活检样本进行分析,并进行网络和通路分析以识别基因表达模式。为证实微阵列研究结果,进行实时定量逆转录聚合酶链反应(qRT-PCR)以评估MZB1和DSC1的信使核糖核酸(mRNA)表达。微阵列和qRT-PCR产生了相似的基因表达变化,证实了微阵列结果在mRNA水平的可靠性。

结果

基因表达微阵列研究结果显示,鉴定出四个显著的基因网络。上调最明显的基因有MZB1、TNFRSF17、PNOC、FCRL5、LAX1、BMS1P20、IGLL5、MMP7、SPAG4和MEI1;下调最明显的基因有LOR、LAMB4、AADACL2、MAPT、ARG1、NPR3、AADAC、DSC1、LRRC4和CHP2。

结论

鉴定出的参与基因网络的基因功能包括细胞发育、细胞生长和增殖、细胞运动、细胞间信号传导和相互作用、体液免疫反应、蛋白质合成、细胞死亡和存活、细胞群体和组织、机体损伤和异常、分子运输以及小分子生物化学。数据表明新的网络在体液免疫反应和机体损伤/异常方面具有重要功能。未来的分析可能有助于进行蛋白质组学分析,以识别与临床结果相关的基因表达模式。

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