An Integrative Pan-Cancer Analysis of PBK in Human Tumors

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.

Identification of PBK as a hub gene and potential therapeutic target for medulloblastoma

“…Previous studies have also reported the overexpression of PBK in multiple cancer types, such as glioma, leukemia, colorectal, ovarian, skin and lung cancer (31,50). Targeting PBK with HI-TOPK-032 or other novel inhibitors, such as OTS514, OTS964 and ADA-07 in these cancer types has shown promising anticancer efficacy as well (31,35).…”

Identification of prognostic value of anoikis‐related gene score model combined with tumor microenvironment score models in esophageal squamous cell carcinoma

“…As a mitotic kinase, PBK/TOPK is important for the proliferation, progression and metastasis of many cancers 23 . Wen et al confirmed that up‐regulation of PBK/TOPK has also been shown to be associated with cancer diagnosis and prognosis, and therefore, it may be a potential therapeutic target for a variety of malignancies 24 . Ohashi et al confirmed that overexpression of PBK/TOPK leads to tumor development and poor prognosis of ESCC 25 .…”

Comprehensive analysis of the potential pathogenesis of COVID-19 infection and liver cancer

“…PBK is highly expressed in cancers such as breast, lung, and leukaemia and is associated with unfavourable prognostic outcomes[ 45 - 47 ]. In addition, PBK was identified as a potential target for a novel anti-SARS-CoV-2 agent[ 48 ], suggesting that PBK has a common potential targeting therapeutic value for cancer and COVID-19. TPX2 is a microtubule-associated protein whose expression is strictly regulated by the cell cycle and participates in cell cycle progression by maintaining the stability of the mitotic spindle[ 49 ].…”