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探索口腔癌的新型计算药物靶点及相关关键信号通路。

Exploring the Novel Computational Drug Target and Associated Key Pathways of Oral Cancer.

作者信息

Akhter Fatema, Kahtani Fawzia Haif Al, Sambawa Zainah Mohammed, Alhassan Deema Abdulrahman, AlSaif Reema Abdulaziz, Haque Tahsinul, Alam Mohammad Khursheed, Hasan Md Tanvir, Islam Md Rakibul, Ahmed Kawsar, Basri Rehana

机构信息

Department of Surgical and Diagnostic Sciences, College of Dentistry, Dar Al Uloom University, Riyadh 13314, Saudi Arabia.

Department of Preventive Sciences, College of Dentistry, Dar Al Uloom University, Riyadh 13314, Saudi Arabia.

出版信息

Curr Issues Mol Biol. 2022 Aug 9;44(8):3552-3572. doi: 10.3390/cimb44080244.

Abstract

Oral cancer (OC) is a serious health concern that has a high fatality rate. The oral cavity has seven kinds of OC, including the lip, tongue, and floor of the mouth, as well as the buccal, hard palate, alveolar, retromolar trigone, and soft palate. The goal of this study is to look into new biomarkers and important pathways that might be used as diagnostic biomarkers and therapeutic candidates in OC. The publicly available repository the Gene Expression Omnibus (GEO) was to the source for the collection of OC-related datasets. GSE74530, GSE23558, and GSE3524 microarray datasets were collected for analysis. Minimum cut-off criteria of |log fold-change (FC)| > 1 and adjusted p < 0.05 were applied to calculate the upregulated and downregulated differential expression genes (DEGs) from the three datasets. After that only common DEGs in all three datasets were collected to apply further analysis. Gene ontology (GO) and pathway analysis were implemented to explore the functional behaviors of DEGs. Then protein−protein interaction (PPI) networks were built to identify the most active genes, and a clustering algorithm was also implemented to identify complex parts of PPI. TF-miRNA networks were also constructed to study OC-associated DEGs in-depth. Finally, top gene performers from PPI networks were used to apply drug signature analysis. After applying filtration and cut-off criteria, 2508, 3377, and 670 DEGs were found for GSE74530, GSE23558, and GSE3524 respectively, and 166 common DEGs were found in every dataset. The GO annotation remarks that most of the DEGs were associated with the terms of type I interferon signaling pathway. The pathways of KEGG reported that the common DEGs are related to the cell cycle and influenza A. The PPI network holds 88 nodes and 492 edges, and CDC6 had the highest number of connections. Four clusters were identified from the PPI. Drug signatures doxorubicin and resveratrol showed high significance according to the hub genes. We anticipate that our bioinformatics research will aid in the definition of OC pathophysiology and the development of new therapies for OC.

摘要

口腔癌(OC)是一个严重的健康问题,死亡率很高。口腔中有七种类型的OC,包括嘴唇、舌头、口腔底部,以及颊部、硬腭、牙槽、磨牙后三角和软腭。本研究的目的是探究新的生物标志物和重要途径,这些标志物和途径可作为OC的诊断生物标志物和治疗候选物。公开可用的基因表达综合数据库(GEO)是收集OC相关数据集的来源。收集了GSE74530、GSE23558和GSE3524微阵列数据集进行分析。应用|log倍数变化(FC)|>1和调整后p<0.05的最小截止标准,从这三个数据集中计算上调和下调的差异表达基因(DEG)。之后,仅收集所有三个数据集中的共同DEG进行进一步分析。实施基因本体(GO)和通路分析以探索DEG的功能行为。然后构建蛋白质-蛋白质相互作用(PPI)网络以识别最活跃的基因,并且还实施聚类算法以识别PPI的复杂部分。还构建了TF-miRNA网络以深入研究OC相关的DEG。最后,使用PPI网络中的顶级基因执行者进行药物特征分析。应用过滤和截止标准后,分别在GSE74530、GSE23558和GSE3524中发现了2508、3377和670个DEG,并且在每个数据集中发现了166个共同DEG。GO注释表明,大多数DEG与I型干扰素信号通路的术语相关。KEGG通路报告称,共同DEG与细胞周期和甲型流感有关。PPI网络有88个节点和492条边,CDC6的连接数最多。从PPI中识别出四个簇。根据枢纽基因,药物特征阿霉素和白藜芦醇显示出高度显著性。我们预计我们的生物信息学研究将有助于定义OC的病理生理学并开发新的OC治疗方法。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7329/9406749/839689a82e51/cimb-44-00244-g001.jpg

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