Identification of key candidate genes and pathways in oral squamous cell carcinoma by integrated Bioinformatics analysis
Identification of key candidate genes and pathways in oral squamous cell carcinoma by integrated Bioinformatics analysis
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通过综合生物信息学分析鉴定口腔鳞状细胞癌的关键候选基因和通路
DOI：
10.3892/etm.2019.7442
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发表时间：
2019-05-01
影响因子：
2.7
通讯作者：
Zhang, Bin
中科院分区：
文献类型：
--
作者：
Zou, Bo;Li, Jun;Zhang, Bin
口腔鳞状细胞癌（Oral squamous cell carcinoma，OSCC）是头颈部最常见的恶性肿瘤之一，严重威胁着人类的健康。近年来，口腔鳞癌的发病率呈上升趋势，但预后并没有明显改善。阐明OSCC发生发展的分子机制可能提供新的治疗策略。本研究对244例口腔鳞状细胞癌和95例正常口腔粘膜组织的基因表达谱进行了统计学和生物信息学分析。共筛选出34个差异表达基因，其中14个在口腔鳞癌组织中表达上调，20个表达下调。基因本体富集分析表明，DEG主要参与免疫应答、细胞粘附和细胞增殖过程的调控。京都基因百科全书和基因组通路分析显示，DEG主要与磷酸肌醇-3激酶Akt和Toll样受体信号通路相关。从复杂的蛋白质-蛋白质相互作用网络中鉴定出关键的候选DEG，并证实分泌型磷蛋白1（SPP 1）、整合素α 3亚基和纤溶酶原激活剂尿激酶（PLAU）与生存率显著相关。Cell Counting Kit-8和Transwell实验表明，SPP 1和PLAU调节细胞增殖、迁移和侵袭。在本研究中确定的候选基因/途径可能包括有前途的诊断生物标志物或治疗目标的口腔鳞癌。
Oral squamous cell carcinoma (OSCC) is one of the most common types of malignant head and neck tumor, which poses a serious threat to human health. In recent years, the incidence of OSCC has been increasing, while the prognosis has not significantly improved. Elucidation of the molecular mechanisms underlying the development of OSCC may provide novel therapeutic strategies. In the present study, the gene expression profiles from 4 datasets, including 244 OSCC and 95 normal oral mucosa samples, were subjected to statistical and Bioinformatics analysis. A total of 34 differentially expressed genes (DEGs) were identified, among which 14 were upregulated and 20 were downregulated in OSCC compared with normal oral mucosa tissues. Gene Ontology enrichment analysis indicated that the DEGs were mainly involved in regulation of the immune response, cell adhesion and cell proliferative processes. The Kyoto Encyclopedia of Genes and Genomes pathway analysis revealed that the DEGs were mainly associated with the phosphoinositide-3 kinase Akt and Toll-like receptor signaling pathway. The key candidate DEGs were identified from the complex protein-protein interaction network, and secreted phosphoprotein 1 (SPP1), integrin subunit α 3 and plasminogen activator, urokinase (PLAU) were confirmed to be significantly associated with the survival rate. Cell Counting Kit-8 and Transwell assays demonstrated that SPP1 and PLAU regulate cell proliferation, migration and invasion. The candidate genes/pathways identified in the present study may include promising diagnostic biomarkers or therapeutic targets for OSCC.