Screening of biomarkers in cervical squamous cell carcinomas via gene expression profiling

Screening of biomarkers in cervical squamous cell carcinomas via gene expression profiling
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DOI:
10.3892/mmr.2015.4322
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发表时间:
2015-11-01
影响因子:
3.4
通讯作者:
Tong, Ying
Tong, Ying
中科院分区:
医学4区
文献类型:
--
作者:
Chen, Bing;Li, Chundong;Tong, Ying

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在本研究中,我们使用生物信息学工具分析了高级别鳞状上皮内病变(HSIL)和侵袭性宫颈鳞状细胞癌(CSCC)的基因表达谱,以确定关键基因和潜在的生物标志物。使用Limma软件包对HSIL与正常对照、侵袭性CSCC与正常对照组织进行差异表达基因(DEGs)分析。利用String构建了侵袭性CSCC中DEGs的蛋白-蛋白相互作用(PPI)网络。使用DAVID对PPI网络中的deg进行功能富集分析。利用Cmap预测相关小分子。HSIL和侵袭性CSCC共鉴定出633和881个deg,两组共有305个deg。与丝裂原激活的蛋白激酶信号通路相关的基因在HSIL中富集,而细胞周期相关基因在侵袭性CSCC中过度表达。PPI网络包含72个上调基因和434个边缘。功能富集分析表明,细胞周期是最重要的基因本体术语。共鉴定出6个与CSCC病理相关的小分子,其中抗癌药物piper-longumine与CSCC呈负相关。本研究的发现不仅增强了目前对CSCC发病机制的理解,而且可能为开发新的治疗方法奠定基础。
In the present study, gene expression profiles of high-grade squamous intraepithelial lesions (HSIL) and invasive cervical squamous cell carcinomas (CSCC) were analyzed using bioinformatic tools to identify key genes and potential biomarkers. Analyses of differentially expressed genes (DEGs) were performed for HSIL vs. normal control and invasive CSCC vs. normal control tissues using the Limma package in R. Pathway enrichment analysis was performed using KOBAS. A protein-protein interaction (PPI) network for the DEGs in invasive CSCC was constructed using String. Functional enrichment analysis was performed for the DEGs in the PPI network using DAVID. Relevant small molecules were predicted using Cmap. A total of 633 and 881 DEGs were identified in HSIL and invasive CSCC, respectively, and the two groups had 305 DEGs in common. Genes associated with the mitogen-activated protein kinase signaling pathway were enriched in the HSIL, while cell cycle-associated genes were over-represented in invasive CSCC. The PPI network, containing 72 upregulated genes and 434 edges, was illustrated. Functional enrichment analysis showed that the cell cycle was the most significant gene ontology term. A total of six small molecules associated with the pathology of CSCC were identified, including the anti-cancer drug piper-longumine, which showed a negative correlation. The findings of the present study not only enhanced the current understanding of the pathogenesis of CSCC, but may also be a basis for the development of novel therapies.