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确定口腔癌、代谢紊乱和牙周病的关键信号通路及新型计算药物靶点。

Identification of key signaling pathways and novel computational drug target for oral cancer, metabolic disorders and periodontal disease.

作者信息

Alam Mohammad Khursheed, Faruk Hosen Md, Ganji Kiran Kumar, Ahmed Kawsar, Bui Francis M

机构信息

Preventive Dentistry Department, College of Dentistry, Jouf University, Sakaka 72345, Saudi Arabia.

Department of Computing Information System, Daffodil International University, Birulia, Savar, Dhaka 1216, Bangladesh.

出版信息

J Genet Eng Biotechnol. 2024 Dec;22(4):100431. doi: 10.1016/j.jgeb.2024.100431. Epub 2024 Oct 22.

Abstract

AIM

Due to conventional endocrinological methods, there is presently no shared work available, and no therapeutic options have been demonstrated in oral cancer (OC) and periodontal disease (PD), type 2 diabetes (T2D), and obese patients. The aim of this study is to determine the similar molecular pathways and potential therapeutic targets in PD, OC, T2D, and obesity that may be used to anticipate the progression of the disease.

METHODS

Four Gene Expression Omnibus (GEO) microarray datasets (GSE29221, GSE15773, GSE16134, and GSE13601) are used for finding differentially expressed genes (DEGs) for T2D, obese, and PD patients with OC in order to explore comparable pathways and therapeutic medications. Gene ontology (GO) and pathway analysis were used to investigate the functional annotations of the genes. The hub genes were then identified using protein-protein interaction (PPI) networks, and the most significant PPI components were evaluated using a clustering approach.

RESULTS

These three gene expression-based datasets yielded a total of seven common DEGs. According to the GO annotation, the majority of the DEGs were connected with the microtubule cytoskeleton structure involved in mitosis. The KEGG pathways revealed that the concordant DEGs are connected to the cell cycle and progesterone-mediated oocyte maturation. Based on topological analysis of the PPI network, major hub genes (CCNB1, BUB1, TTK, PLAT, and AHNAK) and notable modules were revealed. This work additionally identified the connection of TF genes and miRNAs with common DEGs, as well as TF activity.

CONCLUSION

Predictive drug analysis yielded concordant drug compounds involved with T2D, OC, PD, and obesity disorder, which might be beneficial for examining the diagnosis, treatment, and prognosis of metabolic disorders and Oral cancer.

摘要

目的

由于传统内分泌学方法的原因,目前尚无共享的研究成果,且在口腔癌(OC)、牙周病(PD)、2型糖尿病(T2D)和肥胖患者中尚未证实有治疗选择。本研究的目的是确定PD、OC、T2D和肥胖中相似的分子途径和潜在治疗靶点,这些靶点可用于预测疾病进展。

方法

使用四个基因表达综合数据库(GEO)微阵列数据集(GSE29221、GSE15773、GSE16134和GSE13601)来寻找T2D、肥胖以及患有OC的PD患者的差异表达基因(DEG),以探索可比的途径和治疗药物。使用基因本体(GO)和途径分析来研究基因的功能注释。然后使用蛋白质-蛋白质相互作用(PPI)网络鉴定枢纽基因,并使用聚类方法评估最显著的PPI成分。

结果

这三个基于基因表达的数据集总共产生了7个共同的DEG。根据GO注释,大多数DEG与有丝分裂中涉及的微管细胞骨架结构相关。KEGG途径显示,一致的DEG与细胞周期和孕酮介导的卵母细胞成熟相关。基于PPI网络的拓扑分析,揭示了主要的枢纽基因(CCNB1、BUB1、TTK、PLAT和AHNAK)和显著的模块。这项工作还确定了转录因子(TF)基因和微小RNA(miRNA)与共同DEG的联系以及TF活性。

结论

预测性药物分析产生了与T2D、OC、PD和肥胖症相关的一致药物化合物,这可能有助于检查代谢紊乱和口腔癌的诊断、治疗和预后。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/77a9/11539153/69f89c3eff02/gr1.jpg

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