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An Integrative Pan-Cancer Analysis of PBK in Human Tumors
Huantao Wen1, Zitao Chen1, Min Li1
1The National Key Clinical Specialty, The Engineering Technology Research Center of Education Ministry of China, Guangdong Provincial Key Laboratory on Brain Function Repair and Regeneration, Department of Neurosurgery, Zhujiang Hospital, Southern Medical University, Guangzhou, China.
Abstract:
Background: PDZ binding kinase (PBK) is a serine/threonine kinase, which belongs to the mitogen-activated protein kinase kinase (MAPKK) family. It has been shown to be a critical gene in the regulation of mitosis and tumorigenesis, but the role of PBK in various cancers remains unclear. In this study, we systematically explored the prognostic and predictive value of PBK expression in 33 cancer types. Methods: Public databases including the cBioPortal database, GDSC database, GTEx database, CCLE database, and TCGA database were used to detect the PBK expression and its association with the prognosis, clinicopathologic stage, TMB, MSI, immune microenvironment, immune checkpoints, immune cell infiltration, enrichment pathways, and IC50 across pan-cancer. The statistical analyses and visualization were conducted using R software. Results: PBK expression is relatively high in most cancers compared to their normal counterparts, and this gene is barely expressed in normal tissues. High expression of PBK is significantly associated with poor prognosis and clinicopathologic stages I, II, and III in different cancers. Furthermore, PBK expression is strongly associated with TMB in 23 cancer types and associated with MSI in nine cancer types. Moreover, the correlation analysis of the microenvironment and immune cells indicated that PBK is negatively correlated with the immune infiltration levels but positively correlated with the infiltration levels of M0 and M1 macrophages, T cells CD4 memory activated, and T cells follicular helper. GSEA analysis revealed that the biological function or pathways relevant to the cell cycle and mitosis were frequently enriched at the level of high expression of PBK. Conclusion: These results revealed the oncogenic role of PBK, which is significantly upregulated in various cancers and indicated poor prognosis and immune infiltration in multiple cancers. It also suggested that PBK may serve as a biomarker in multiple tumor progress and patient survival.
Insights
PDZ binding kinase (PBK) is highly expressed in most cancers, correlating with poor prognosis and altered immune infiltration. This study highlights PBK
Area of Science:
- Oncology
- Molecular Biology
- Cancer Genomics
Background:
- PDZ binding kinase (PBK) is a serine/threonine kinase in the MAPKK family.
- PBK is implicated in mitosis regulation and tumorigenesis, but its pan-cancer role is unclear.
Purpose of the Study:
- To systematically investigate the prognostic and predictive value of PBK expression across 33 cancer types.
- To explore PBK's association with clinicopathologic features, tumor mutational burden (TMB), microsatellite instability (MSI), and the tumor immune microenvironment.
Main Methods:
- Utilized public databases (cBioPortal, TCGA, GTEx, etc.) for expression and association analyses.
- Performed statistical analyses and visualization using R software.
- Included assessment of TMB, MSI, immune cell infiltration, and pathway enrichment (GSEA).
Main Results:
- PBK is upregulated in most cancers compared to normal tissues and linked to poor prognosis and advanced stages (I-III).
- PBK expression correlates with TMB in 23 cancers and MSI in nine.
- PBK shows complex associations with immune infiltration, negatively correlating overall but positively with M0/M1 macrophages and specific T cell subsets.
Conclusions:
- PBK exhibits an oncogenic role, with high expression indicating poor prognosis and altered immune infiltration in multiple cancers.
- PBK may serve as a potential biomarker for tumor progression and patient survival.
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