Published online Apr 24, 2019. doi: 10.5306/wjco.v10.i4.166
Peer-review started: December 3, 2018
First decision: December 30, 2018
Revised: January 25, 2019
Accepted: February 27, 2019
Article in press: February 28, 2019
Published online: April 24, 2019
Aberrant activation of phosphorylated form of glycogen synthase kinase-3β [pS9GSK-3β (Serine 9 phosphorylation)] is known to trigger Wnt/β-catenin signal cascade.
The clinicohistopathological implications of glycogen synthase kinase-3β [pS9GSK-3β (Serine 9 phosphorylation)]/β-catenin in bladder carcinogenesis remain unknown.
The aim of the present study is to investigate the diagnostic and prognostic relevance of expressions of pS9GSK-3β, β-catenin and its target genes in the pathobiology of bladder cancer.
Cellular localization and the expression of pS9GSK-3β proteins were examined by immunohistochemical (IHC) staining in ninety tumor tissues resected from patients diagnosed with bladder cancer. Real time-quantitative polymerase chain reaction and IHC were done to check the expression of β-catenin, Cyclin D1, Snail and Slug at transcriptome and protein level respectively. Expressions of the markers were statistically correlated with these variables to determine their significance in clinical setting.
Aberrant (low or no membranous/high nuclear/high cytoplasmic) expression of pS9GSK-3β was noted in 51% patients and found to be significantly associated with tumor stage and tumor grade. Thirty one percent tumors exhibited aberrant co-expression of pS9GSK-3β and β–catenin proteins and showed strong statistical association with tumor stage (P = 0.01), tumor type (P = 0.02), smoking/tobacco chewing status (0.04) and shorter overall survival probabilities of patients (P = 0.02).
Findings of the present study strongly support the involvement of pS9GSK-3β in urothelial tumorigenesis by stabilizing β-catenin. Statistical association of aberrantly co-expressed pS9GSK-3β and β–catenin proteins with patients’ variables validates them as potential markers of clinical relevance in the pathobiology of bladder cancer.
Results based on the association/correlation studies between the expression levels of marker proteins and clinicohistopathological variables indicate that aberrantly expressed pS9GSK-3β participates in neoplastic transformation by stabilizing β-catenin during urothelial tumorigenesis and could be considered as potential prognostic marker.