Clinicohistopathological implications of phosphoserine 9 glycogen synthase kinase-3β/ β-catenin in urinary bladder cancer patients

doi:10.5306/wjco.v10.i4.166

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World Journal of Clinical Oncology

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World J Clin Oncol. Apr 24, 2019; 10(4): 166-182
Published online Apr 24, 2019. doi: 10.5306/wjco.v10.i4.166

Clinicohistopathological implications of phosphoserine 9 glycogen synthase kinase-3β/ β-catenin in urinary bladder cancer patients

Niharika Maurya, Rinni Singh, Apul Goel, Atin Singhai, Uday Pratap Singh, Vinita Agrawal, Minal Garg

Niharika Maurya, Rinni Singh, Minal Garg, Department of Biochemistry, Lucknow University, Lucknow 226007, India

Apul Goel, Department of Urology, King George Medical University, Lucknow 226003, India

Atin Singhai, Department of Pathology, King George Medical University, Lucknow 226003, India

Uday Pratap Singh, Department of Urology and Renal Transplantation, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Lucknow 226014, India

Vinita Agrawal, Department of Pathology, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Lucknow 226014, India

Author contributions: All authors contributed to this paper; all the authors have agreed with the submission in its present form.

Institutional review board statement: Studies were approved by the appropriate institutional research ethics committee and were performed in accordance with the ethical standards as laid down in the 1964 Declaration of Helsinki and its later amendments or comparable ethical standards. Ethical clearance was obtained from Bioethics Cell, Institutional Ethics Committee (IEC), KGMU (Reference no. 77^th ECM II A/P14) and SGPGIMS (Reference no. 2014-166-CP-80), Lucknow, India.

Informed consent statement: Subjects were not required to give informed consent to the study because the analysis used anonymous data that were obtained after each patient agreed to treatment by written consent.

Conflict-of-interest statement: All the authors of the study declare no potential conflict-of-interest.

Corresponding author: Minal Garg, MSc, PhD, Assistant Professor, Department of Biochemistry, Lucknow University, Lucknow 226007, India. minal14@yahoo.com

Telephone: +91-522-2348968 Fax: +91-522-2348968

Received: December 2, 2018
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
Processing time: 145 Days and 7.1 Hours

ARTICLE HIGHLIGHTS

Research background

Aberrant activation of phosphorylated form of glycogen synthase kinase-3β [pS9GSK-3β (Serine 9 phosphorylation)] is known to trigger Wnt/β-catenin signal cascade.

Research motivation

The clinicohistopathological implications of glycogen synthase kinase-3β [pS9GSK-3β (Serine 9 phosphorylation)]/β-catenin in bladder carcinogenesis remain unknown.

Research objectives

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.

Research methods

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.

Research results

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).

Research conclusions

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.

Research perspectives

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.