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识别与宫颈鳞状细胞癌进展和预后相关的关键基因。

Identification of Key Genes in Association with Progression and Prognosis in Cervical Squamous Cell Carcinoma.

机构信息

Department of Gynecology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.

出版信息

DNA Cell Biol. 2020 May;39(5):848-863. doi: 10.1089/dna.2019.5202. Epub 2020 Mar 23.

Abstract

Cervical cancer remains a primary cause of female death in developing countries, but its prognosis can be greatly improved if patients are diagnosed earlier. In the present study, we screened the common differentially expressed genes (DEGs) of cervical squamous cell carcinoma (CESC) from dataset GSE7803, Gene Expression Omnibus, and The Cancer Genome Atlas databases. An integrated bioinformatics analysis was performed based on these DEGs for their enrichment in functions and pathways, interaction network, prognostic signature, and candidate molecular drugs. As a result, 164 (114 upregulated and 47 downregulated) DEGs of CESC were identified for further investigation. We then conducted the gene ontology term enrichment and Kyoto Encyclopedia of Genes and Genomes Pathway analyses to reveal the underlying functions and pathways of these DEGs. In the protein-protein interaction network, hub module and hub genes were identified. Five genes of significant prognostic value-, , , , and -were identified by prognostic signature analysis and used to construct a risk linear model. Further validation and investigation suggested might be a key gene in CESC prognosis. We then identified two candidate small molecules (trichostatin A and tanespimycin) against CESC. Further validation and exploration of these hub genes are warranted for future prospect in clinical applications.

摘要

宫颈癌仍然是发展中国家女性死亡的主要原因,但如果患者能更早被诊断出来,其预后可以大大改善。本研究从 GEO 数据库和 TCGA 数据库中筛选了宫颈癌(CESC)的常见差异表达基因(DEGs)数据集 GSE7803。基于这些 DEGs 进行了综合的生物信息学分析,以研究它们在功能和途径、相互作用网络、预后特征和候选分子药物方面的富集情况。结果,确定了 164 个(114 个上调和 47 个下调)CESC 的 DEGs 进行进一步研究。然后,我们进行了基因本体论术语富集和京都基因与基因组百科全书通路分析,以揭示这些 DEGs 的潜在功能和通路。在蛋白质-蛋白质相互作用网络中,鉴定出了枢纽模块和枢纽基因。通过预后特征分析,鉴定出了 5 个具有显著预后价值的基因-、、、和-,并用于构建风险线性模型。进一步的验证和研究表明,可能是 CESC 预后的关键基因。然后,我们鉴定了两种针对 CESC 的候选小分子(曲古抑菌素 A 和坦西普霉素)。未来有必要对这些枢纽基因进行进一步的验证和探索,以应用于临床。

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