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与原发性涎腺癌发病机制相关的潜在生物标志物和信号通路:一项生物信息学研究

Potential biomarkers and signaling pathways associated with the pathogenesis of primary salivary gland carcinoma: a bioinformatics study.

作者信息

Bayat Zeynab, Ahmadi-Motamayel Fatemeh, Parsa Mohadeseh Salimi, Taherkhani Amir

机构信息

Department of Oral and Maxillofacial Medicine, Faculty of Dentistry, Hamadan University of Medical Sciences, Hamadan 6517838678, Iran.

Dental Implants Research Center and Dental Research Center, Department of Oral Medicine, Hamadan University of Medical Sciences, Hamadan 6517838678, Iran.

出版信息

Genomics Inform. 2021 Dec;19(4):e42. doi: 10.5808/gi.21052. Epub 2021 Dec 31.

Abstract

Salivary gland carcinoma (SGC) is rare cancer, constituting 6% of neoplasms in the head and neck area. The most responsible genes and pathways involved in the pathology of this disorder have not been fully understood. We aimed to identify differentially expressed genes (DEGs), the most critical hub genes, transcription factors, signaling pathways, and biological processes (BPs) associated with the pathogenesis of primary SGC. The mRNA dataset GSE153283 in the Gene Expression Omnibus database was re-analyzed for determining DEGs in cancer tissue of patients with primary SGC compared to the adjacent normal tissue (adjusted p-value < 0.001; |Log2 fold change| > 1). A protein interaction map (PIM) was built, and the main modules within the network were identified and focused on the different pathways and BP analyses. The hub genes of PIM were discovered, and their associated gene regulatory network was built to determine the master regulators involved in the pathogenesis of primary SGC. A total of 137 genes were found to be differentially expressed in primary SGC. The most significant pathways and BPs that were deregulated in the primary disease condition were associated with the cell cycle and fibroblast proliferation procedures. TP53, EGF, FN1, NOTCH1, EZH2, COL1A1, SPP1, CDKN2A, WNT5A, PDGFRB, CCNB1, and H2AFX were demonstrated to be the most critical genes linked with the primary SGC. SPIB, FOXM1, and POLR2A significantly regulate all the hub genes. This study illustrated several hub genes and their master regulators that might be appropriate targets for the therapeutic aims of primary SGC.

摘要

涎腺癌(SGC)是一种罕见的癌症,占头颈部肿瘤的6%。该疾病病理过程中最主要的相关基因和信号通路尚未完全明确。我们旨在鉴定与原发性SGC发病机制相关的差异表达基因(DEG)、最关键的枢纽基因、转录因子、信号通路及生物学过程(BP)。重新分析了基因表达综合数据库中的mRNA数据集GSE153283,以确定原发性SGC患者癌组织与相邻正常组织相比的DEG(校正p值<0.001;|Log2倍数变化|>1)。构建了蛋白质相互作用图谱(PIM),识别了网络中的主要模块,并着重进行不同通路和BP分析。发现了PIM的枢纽基因,并构建了其相关的基因调控网络,以确定参与原发性SGC发病机制的主要调控因子。共发现137个基因在原发性SGC中差异表达。在原发性疾病状态下失调最显著的通路和BP与细胞周期及成纤维细胞增殖过程相关。TP53、EGF、FN1、NOTCH1、EZH2、COL1A1、SPP1、CDKN2A、WNT5A、PDGFRB、CCNB1和H2AFX被证明是与原发性SGC相关的最关键基因。SPIB、FOXM1和POLR2A显著调控所有枢纽基因。本研究阐明了几个枢纽基因及其主要调控因子,它们可能是原发性SGC治疗目标的合适靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9e72/8752977/855b4a5310a4/gi-21052f1.jpg

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