基于生物信息学分析的头颈部鳞状细胞癌中 PLEK2 的表达及预后潜能。
Expression and prognostic potential of PLEK2 in head and neck squamous cell carcinoma based on bioinformatics analysis.
机构信息
Department of Radiation Oncology, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong Province, People's Republic of China.
State Key Laboratory of Oncology in South China, Guangzhou, Guangdong Province, People's Republic of China.
出版信息
Cancer Med. 2021 Sep;10(18):6515-6533. doi: 10.1002/cam4.4163. Epub 2021 Jul 30.
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.
背景
PLEK2（pleckstrin）可以与膜结合的磷脂酰肌醇结合，并进一步促进细胞铺展。最近，几项研究指出了 PLEK2 在肿瘤转移中的重要性。然而，PLEK2 在头颈部鳞状细胞癌（HNSCC）中的作用仍有待阐明。
方法
使用 Oncomine、基因表达综合数据库（GEO）、UALCAN 数据库和 Western blot 分析鉴定 HNSCC 中的 PLEK2 表达。使用 Kaplan-Meier plotter、DriverDBv3、UALCAN、UCSC Xena 和 GEO 数据库进行预后分析。进一步使用 cancerSEA 数据库进行单细胞功能分析。鉴定 PLEK2 相关共表达基因，并使用 LinkedOmics 进行基因集富集分析。然后，使用 Cytoscape 的 cytoHubba 插件鉴定前 10 个枢纽基因。然后，使用 R 包“clusterProfiler”和 GSCAlite 对枢纽基因进行基因富集分析、通路活性和药物敏感性分析。最后，使用 UCSC Xena 浏览器探索最有可能与 HNSCC 中的 PLEK2 发挥协同作用的枢纽基因。
结果
在 HNSCC 中观察到 PLEK2 的表达升高，甚至在基于不同临床病理特征的 HNSCC 亚组中也是如此，预示着 HNSCC 的预后不良。PLEK2 与 HNSCC 的转移和缺氧相关，与 PLEK2 相关的共表达基因主要参与焦点粘连途径。前 10 个枢纽基因主要富集在焦点粘连、HPV 感染、ECM-受体相互作用和 PI3K-AKT 信号通路以及上皮-间充质转化通路中，并且激活了该通路。此外，枢纽基因的表达水平与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 可能被视为促进 HNSCC 转移的密不可分的因素。
结论
总的来说，PLEK2 可能作为 HNSCC 诊断的潜在生物标志物，并指导 HNSCC 的靶向治疗开发。
Zotero 插件