The Correlation of PBK Expression with an Immune-Activated Tumor Microenvironment and Outcome in Colorectal Cancer

TL;DR

High PBK expression in colorectal cancer is linked to a more active immune environment and better patient outcomes.

Contribution

PBK is identified as a novel prognostic biomarker in colorectal cancer associated with immune activation and favorable outcomes.

Findings

High PBK expression correlates with lower tumor stage and absence of vascular invasion.

PBK-positive tumors show increased immune cell infiltration and better survival rates.

PBK is mainly expressed in proliferative tumor epithelial cells.

Abstract

Colorectal cancer shows large differences in patient outcomes, partly because tumors vary in their biological and immune characteristics. Identifying markers that reflect these differences is important for improving prognosis and treatment strategies. PDZ-binding kinase (PBK) is a protein involved in cell division and has been linked to cancer progression, but its clinical significance in colorectal cancer remains unclear. In this study, we examined PBK expression in tumor tissues from patients with colorectal cancer and analyzed its relationship with tumor features, immune cell infiltration, and patient survival. We found that tumors with high PBK expression were associated with a more active immune environment and better clinical outcomes. These findings suggest that PBK expression may help identify colorectal cancer patients with a favorable immune response and prognosis, providing useful information for future research and potential treatment stratification.

Background/Objectives: PDZ-binding kinase (PBK) regulates mitosis, but its clinical significance and cellular localization in colorectal cancer (CRC) remain unclear. We evaluated PBK expression in CRC tissues and examined its association with clinicopathological features, immune contexture, and outcomes. Methods: PBK expression was assessed by RNA in situ hybridization in tumors from 246 CRC patients. Associations with TNM stage, vascular invasion, MMR status (dMMR/pMMR), immune cell infiltration, and stromal programmed death-ligand 1 (PD-L1) were analyzed. Overall survival (OS) and recurrence-free survival (RFS) were evaluated using Kaplan–Meier and Cox models. Public single-cell RNA sequencing datasets were analyzed to identify PBK-expressing cell populations. Results: Among 246 cases, 75 (30.5%) showed high PBK expression. High PBK expression was associated with lower TNM stage, absence of vascular invasion, and dMMR status. High-PBK tumors showed an immune-activated microenvironment, including increased CD4+, CD8+, and FOXP3+ T-cell infiltration, higher stromal PD-L1 expression, and higher tumor-infiltrating lymphocyte scores. Single-cell analysis indicated that PBK expression was enriched mainly in proliferative tumor epithelial cell populations. High PBK expression was associated with longer OS and RFS and remained an independent favorable prognostic factor in multivariate analysis. Conclusions: PBK expression in CRC is linked to proliferative tumor epithelial states, an immune-activated microenvironment, and favorable outcomes, supporting its utility as a prognostic biomarker.

Figures