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慢性牙周炎与口腔鳞状细胞癌之间的共享遗传和表观遗传机制。

Shared genetic and epigenetic mechanisms between chronic periodontitis and oral squamous cell carcinoma.

机构信息

Department of Cariology, Endodontology and Periodontology, University Leipzig, Liebigstr. 12, 04103 Leipzig, Germany.

College of Bioinformatics Science and Technology, Harbin Medical University, Harbin, Heilongjiang Province, China; Shanghai Genomap Technologies, Kongjiang Road 1500, Yangpu District, Shanghai, China.

出版信息

Oral Oncol. 2018 Nov;86:216-224. doi: 10.1016/j.oraloncology.2018.09.029. Epub 2018 Oct 3.

Abstract

OBJECTIVES

To analyze bioinformatic datasets for detecting genetic and epigenetic mechanisms shared by chronic periodontitis (CP) and oral squamous cell carcinoma (OSCC).

MATERIALS AND METHODS

Datasets from GEO and TCGA databases reporting mRNAs, miRNAs or methylation expression in human CP and OSCC tissues were analyzed. Differential expression, functional enrichment and protein-protein interaction (PPI) network analyses were performed. Differentially expressed miRNAs (DEmiRNAs) and genes (DEG) in CP and OSCC were determined. DEmiRNA-target and DEmiRNA-DEG networks were constructed. Directly and indirectly interacting cross-talk genes were screened, and their prediction accuracy and association with OSCC prognosis was determined.

RESULTS

3 DE-miRNAs (miR-375, miR-3609 and miR-3652) expressed in both CP and OSCC critically regulated most DEGs. Among 12 directly interacting cross-talk genes, NCAPH was significantly related with the prognosis of OSCC. NR2F2 had highest differential expression in CP and OSCC. Among 4 cross-talk genes (FN1, MPPED1, NDEL1, and NR2F2) differentially expressed in CP, 3 (FN1, MPPED1, NDEL1) were also expressed in OSCC. Among 12 indirectly interacting cross-talk genes differentially expressed in OSCC, 3 genes (CDCA8, HIST1H3J, and RAD51) were significantly related to its prognosis. Significant pathways involved in CP and OSCC included: chemokine receptors, class I PI3K signaling events, epithelial-to-mesenchymal transition and signaling events by VEGFR1 and VEGFR2, EGF receptor (ErbB1).

CONCLUSION

Bioinformatic analysis of available datasets implicated 1 directly interacting cross-talk gene (NCAPH), 4 indirectly interacting cross-talk genes (NCAPH, NR2F2, FN1, and MPPED1) and 3 DE-miRNAs (hsa-miR-375, miR-3609 and miR-3652) as shared genetic and epigenetic expression patterns between CP and OSCC.

摘要

目的

分析慢性牙周炎 (CP) 和口腔鳞状细胞癌 (OSCC) 共享的遗传和表观遗传机制的生物信息数据集。

材料与方法

分析了 GEO 和 TCGA 数据库中报告的人类 CP 和 OSCC 组织中 mRNA、miRNA 或甲基化表达的数据集。进行了差异表达、功能富集和蛋白质-蛋白质相互作用 (PPI) 网络分析。确定 CP 和 OSCC 中的差异表达 miRNA (DEmiRNA) 和基因 (DEG)。构建 DEmiRNA-靶和 DEmiRNA-DEG 网络。筛选直接和间接相互作用的交叉对话基因,并确定其预测准确性及其与 OSCC 预后的关系。

结果

在 CP 和 OSCC 中表达的 3 个 DE-miRNA(miR-375、miR-3609 和 miR-3652)关键调控大多数 DEG。在 12 个直接相互作用的交叉对话基因中,NCAPH 与 OSCC 的预后显著相关。NR2F2 在 CP 和 OSCC 中的差异表达最高。在 CP 中差异表达的 4 个交叉对话基因(FN1、MPPED1、NDEL1 和 NR2F2)中,有 3 个(FN1、MPPED1、NDEL1)在 OSCC 中也有表达。在 OSCC 中差异表达的 12 个间接相互作用的交叉对话基因中,有 3 个基因(CDCA8、HIST1H3J 和 RAD51)与 OSCC 的预后显著相关。涉及 CP 和 OSCC 的重要途径包括:趋化因子受体、I 类 PI3K 信号事件、上皮-间质转化以及 VEGFR1 和 VEGFR2、表皮生长因子受体 (ErbB1) 的信号事件。

结论

对现有数据集的生物信息学分析表明,1 个直接相互作用的交叉对话基因(NCAPH)、4 个间接相互作用的交叉对话基因(NCAPH、NR2F2、FN1 和 MPPED1)和 3 个 DE-miRNA(hsa-miR-375、miR-3609 和 miR-3652)作为 CP 和 OSCC 之间共享的遗传和表观遗传表达模式。

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