Journal: The Journal of clinical endocrinology and metabolism
This study evaluates PDZ-binding kinase (PBK) as a biomarker and potential therapeutic target in pheochromocytomas and paragangliomas (PPGLs), focusing on metastatic risk.
Using public transcriptomic datasets and validation in clinical PPGL cohorts, the authors identified PBK as a metastasis-associated molecule. Higher PBK expression correlated with:
- Presence of metastasis
- Higher Ki-67 labeling index
- SDHB mutations
- Shorter metastasis-free survival
They defined a “PBK index” as the percentage of tumor cells with positive PBK staining. In multivariate logistic regression, the PBK index remained an independent predictor of metastasis (odds ratio 1.40, P = .016) after adjustment for established risk factors. A PBK index ≥3% notably enhanced metastasis prediction when added to existing models, achieving an AUC of 0.951.
Mechanistic work in PC-12 cells showed that PBK knockdown reduced cell viability, induced S-phase arrest, and increased p53 and p21 expression. PBK silencing also diminished migration and invasion, associated with reduced MMP2/9 expression, interference with epithelial–mesenchymal transition, and inhibition of multiple oncogenic pathways (including MAPK, Rap1, and TGF-β signaling).
Overall, PBK is proposed as a novel metastasis-related biomarker in PPGLs, and its immunohistochemical index may refine risk stratification. PBK also emerges as a plausible therapeutic target based on its functional role in proliferation and invasion.