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.
Highlights
Cancer is the second most frequent cause of death worldwide and emerges in various forms according to cells of origin and the genomic alterations (Pan-cancer analysis of whole genomes 2020; Bray et al, 2013; Weinstein et al, 2013)
The expression of PDZ binding kinase (PBK) in 21 tumor cell lines based on the CCLE database showed that PBK displayed inconsistent expression levels across tumor cell lines (p 2.2e-16, Figure 1B), and the expression of the PBK level was relatively high in tumor cells
We compared the difference of PBK mRNA expression between cancer and normal tissues on The Cancer Genome Atlas (TCGA) database, and the results showed that PBK was relatively highly expressed in most tumor tissues (p < 0.05), except for SKCM, THYM, and READ (Figure 1C)
Summary
Cancer is the second most frequent cause of death worldwide and emerges in various forms according to cells of origin and the genomic alterations (Pan-cancer analysis of whole genomes 2020; Bray et al, 2013; Weinstein et al, 2013). Calculation by repetitive timing and gene expression associated with background mutation rates enabled us to reduce false-positive and false-negative rates in statistics in a single type of tumor project (Lawrence et al, 2013; Weinstein et al, 2013). This helps us to comprehensively understand certain gene expression levels in cancer and the implication for cancer treatment in clinical practice. We systematically explored the prognostic and predictive value of PBK expression in 33 cancer types
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