背景:PLEK2(pleckstrin)可与膜结合磷脂酰肌醇结合并进一步促进细胞扩散。最近,一些研究已经注意到PLEK2在肿瘤转移中的重要性。然而,PLEK2在头颈部鳞状细胞癌(HNSCC)中的作用尚待阐明。
方法:使用Oncomine鉴定HNSCC中的PLEK2表达,基因表达综合(GEO),UALCAN数据库,和蛋白质印迹分析。预后分析采用Kaplan-Meier绘图仪,DriverDBv3,UALCAN,UCSCXena,和GEO数据库。使用cancerSEA数据库进一步进行单细胞功能分析。鉴定了与PLEK2相关的共表达基因,使用LinkedOmics进行基因集富集分析。此外,使用Cytoscape的cytoHubba插件鉴定了前10个hub基因。然后,基因富集分析,通路活性,使用R包“clusterProfiler”和GSCAlite对hub基因进行药物敏感性分析。最后,UCSCXena浏览器用于探索HNSCC中最有可能与PLEK2发挥协同作用的hub基因.
结果:根据不同的临床病理特征,在HNSCC甚至HNSCC亚组中观察到PLEK2的表达升高,预示HNSCC预后不良。PLEK2与HNSCC的转移和缺氧有关,PLEK2相关共表达基因主要参与粘着斑途径。前10个hub基因主要富集于粘着斑,HPV感染,ECM-受体相互作用,和PI3K-AKT信号通路,上皮-间质转化途径被激活。此外,hub基因的表达水平与对各种小分子和抗癌药物的敏感性和耐药性相关。进一步的研究表明,ITGA3和PLEK2可能被认为是促进HNSCC转移的不可分割的联系。
结论:一般来说,PLEK2可能作为HNSCC诊断的潜在生物标志物,并指导HNSCC靶向治疗的开发。
BACKGROUND: PLEK2 (pleckstrin) could bind to membrane-bound phosphatidylinositols and further promote cell spread. Recently, several studies have noted the importance of PLEK2 in tumor metastasis. However, the role of PLEK2 in head and neck squamous cell carcinoma (HNSCC) remains to be elucidated.
METHODS: The PLEK2 expression in HNSCC was identified using Oncomine, Gene Expression Omnibus (GEO), UALCAN databases, and western blot analysis. Prognosis analysis was performed using Kaplan-Meier plotter, DriverDBv3, UALCAN, UCSC Xena, and GEO databases. Single-cell functional analysis was further performed using the cancerSEA database. The PLEK2-related co-expressed genes were identified, and gene set enrichment analysis was performed using LinkedOmics. Furthermore, the top 10 hub genes were identified using the cytoHubba plug-in of Cytoscape. Then, gene enrichment analysis, pathway activity, and drug sensitivity analyses of the hub genes were performed using the R package \"clusterProfiler\" and GSCAlite. Finally, the UCSC Xena browser was utilized to explore the hub gene most likely to play a synergic role with PLEK2 in HNSCC.
RESULTS: Elevated expression of PLEK2 was observed in HNSCC and even in HNSCC subgroups based on diverse clinicopathological features, portending a poor prognosis in HNSCC. PLEK2 was correlated with metastasis and hypoxia in HNSCC, and the PLEK2-related co-expressed genes were mainly involved in the focal adhesion pathway. The top 10 hub genes were primarily enriched in focal adhesion, HPV infection, ECM-receptor interaction, and PI3K-AKT signaling pathway, and epithelial-mesenchymal transition pathway was activated. Furthermore, the expression levels of the hub genes were associated with sensitivity and resistance to various small molecules and anti-cancer drugs. Further study suggested that
ITGA3 and PLEK2 might be viewed as inextricably linked in facilitating HNSCC metastasis.
CONCLUSIONS: In general, PLEK2 might serve as a potential biomarker for the diagnosis of HNSCC and guide the development of targeted therapies for HNSCC.