PBK Expression Is Associated With Prognosis of Patients With Oral Squamous Cell Carcinoma Treated With Radiotherapy: A Retrospective Study

Abstract

Background/Aim: To investigate the impact of PDZ-binding kinase (PBK) on the clinical outcome of patients with oral squamous cell carcinoma (OSCC) who received radiotherapy. Patients and Methods: PBK immunoreactivity of cancer specimens obtained from 179 patients with primary OSCC was analyzed by immunohistochemistry. Results: High PBK expression in tumor cells tended to be associated with advanced N-stage. The 5-year survival rate was greater for patients with high total PBK expression than in those with low PBK expression. After adjustment, high PBK remained associated with a favorable outcome. In subgroups according to tumor stage, the prognostic role was significant in patients with stage III/IV rather than those with stage I/II disease. Conclusion: We suggest that PBK expression should be used as an independent prognostic marker for patients with OSCC treated with radiotherapy, especially for those with advancedstage disease.Oral squamous cell carcinomas (OSCCs) are the most common among all head and neck squamous cell cancers (1). In 2020, cancer of the lip and oral cavity accounted for more than 377,713 cases and 177,757 deaths worldwide (2). Individuals from developing countries where there is higher number of risk factors, such as smoking, betel nut chewing, and alcohol consumption, are at an increased risk for developing OSCC. In Taiwan, OSCC is the fourth common cancer type (approximate incidence rate of 29 per 100,000 population and mortality of 32 per 100,000 population) and the second cancer type with the fastest increasing incidence (3). The Surveillance, Epidemiology, and End Results Cancer Statistics Review reported that the 5-year relative survival rate patients with locally advanced oral cavity and oropharyngeal cancer is 54.7% whereas it is 82.5% for those with early-stage disease (4).Many efforts have been made to identify biomarkers or specific genes that might provide useful information for clinical patient management. The complex pathogenesis of oral cancer is driven by DNA-repair genes, tumor-suppressor genes, and well-recognized factors, such as alcohol, betel nut chewing, and viral infection (5, 6). PDZ-binding kinase (PBK), also known as lymphokine-activated killer T-celloriginated protein kinase, is a mitogen-activated protein kinase kinase-like serine/threonine kinase that is involved in cell-cycle regulation via a cyclin B1-dependent manner, and in mitotic progression (7-9). PBK is found in proliferative tissues, such as testis, fetal, and neuronal stem cells; studies have found PBK overexpression in various malignancies, such as leukemia, Burkitt's lymphoma, breast cancer, and lung cancer (10-13). PBK is up-regulated in tumors; however, reports on the clinical significance of PBK are lacking. Our previous research showed the unfavorable 2177 *These Authors contributed equally to this study.

PDZ Binding Kinase/T-LAK Cell-Derived Protein Kinase Plays an Oncogenic Role and Promotes Immune Escape in Human Tumors

“…Although previous studies [1,26,27] have reported higher expression of the PBK/TOPK mRNA and protein in tumor tissues than in adjacent noncancerous tissues from different tumors, this study was the first pan-cancer analysis of PBK/ TOPK and enabled us to observe the expression across all cancers. We only detected lower PBK/TOPK mRNA expression in LAML tissues than in normal tissues, which has not been reported in previous studies, although PBK/TOPK may mediate cell proliferation and viability in promyelocyte cell lines [28].…”

Omics- and Pharmacogenomic Evidence for the Prognostic, Regulatory, and Immune-Related Roles of PBK in a Pan-Cancer Cohort

“…Additionally, PBK promotes cell migration by regulating phosphatidylinositol 3-kinase (PI3K)/phosphatase and tensin homolog (PTEN)/protein kinase B (AKT) or transforming growth factor beta 1 (TGF-β1)/mothers against decapentaplegic (Smad) signaling pathways ( Shih et al, 2012 ; Lee et al, 2020 ). PBK is differentially expressed between cancer and normal tissues and modulates radiosensitivity in tumors, suggesting that patients can be treated with radiotherapy ( Pirovano et al, 2017 ); and a recent retrospective analysis showed that PBK expression was negatively correlated with the prognosis of patients with oral squamous cell carcinoma treated with radiotherapy ( Yu et al, 2021 ). The PBK inhibitor OTS964/OTS514 was shown to inhibit cytokinesis and cancer cell growth ( Matsuo et al, 2014 ), and OTS964/OTS514 induced the apoptosis of lung cancer cells including small cell lung cancer (SCLC) cells ( Park et al, 2017 ).…”

Centromere protein E as a novel biomarker and potential therapeutic target for retinoblastoma

“…PBK was initially identified as a serine/threonine protein kinase for mitogen-activated protein kinase and is associated with cytokinesis and spermatogenesis[ 64 ]. PBK has been suggested as a promising prognostic predictor for patients with oral squamous cell carcinoma treated with radiotherapy[ 65 ]. PBK can enhance aggressive phenotypes of cervical cancer by regulating the ERK/c-Myc signaling pathway[ 66 ].…”