Expression and prognostic potential of PLEK2 in head and neck squamous cell carcinoma based on bioinformatics analysis

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.

Automated summary

Elevated expression of PLEK2 was observed in HNSCC, correlated with metastasis and hypoxia, and associated with the focal adhesion pathway. PLEK2 and ITGA3 may be viewed as intricately linked in facilitating HNSCC metastasis.