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

作　　者：Niharika Maurya Rinni Singh Apul Goel Atin Singhai Uday Pratap Singh Vinita Agrawal Minal Garg 

机构地区：[1]Department of Biochemistry, Lucknow University [2]Department of Urology, King George Medical University [3]Department of Pathology, King George Medical University [4]Department of Urology and Renal Transplantation, Sanjay Gandhi Post Graduate Institute of Medical Sciences [5]Department of Pathology, Sanjay Gandhi Post Graduate Institute of Medical Sciences

出　　处：《World Journal of Clinical Oncology》2019年第4期166-182,共17页世界临床肿瘤学杂志（英文版）

摘　　要：BACKGROUND Aberrant activation of phosphorylated form of glycogen synthase kinase-3β[pS9 GSK-3β(Serine 9 phosphorylation)] is known to trigger Wnt/β-catenin signal cascade but its clinicohistopathological implications in bladder carcinogenesis remain unknown.AIM To investigate the diagnostic and prognostic relevance of expressions of pS9 GSK-3β, β-catenin and its target genes in the pathobiology of bladder cancer.METHODS Bladder tumor tissues from ninety patients were analyzed for quantitative expression and cellular localization of pS9 GSK-3β by immunohistochemical(IHC) staining. 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. Clinicohistopathological variables were obtained from histology reports, follow up and OPD visits of patients.Expressions of the markers were statistically correlated with these variables to determine their significance in clinical setting. Results were analysed using SPSS20.0 software.RESULTS Aberrant(low or no membranous/high nuclear/high cytoplasmic) expression of pS9 GSK-3β was noted in 51% patients and found to be significantly associated with tumor stage and tumor grade(P = 0.01 and 0.04; Mann Whitney U test).Thirty one percent tumors exhibited aberrant co-expression of pS9 GSK-3β andβ–catenin proteins and showed strong statistical association with tumor stage,tumor type, smoking/tobacco chewing status(P = 0.01, 0.02 and 0.04, MannWhitney U test) and shorter overall survival probabilities of patients(P = 0.02;Kaplan Meier test). Nuclear immunostaining of Cyclin D1 in tumors with altered pS9 GSK-3β/β–catenin showed relevance with tumor stage, grade and type.CONCLUSIONβ–catenin and pS9 GSK-3β proteins are identified as markers of diagnostic/prognostic significance in disease pathogenesis. Observed histopathological association of Cyclin D1 identifies it as marker of potential relevance in tumors with altered pS9 GSK-3β/β-catenin.BACKGROUND Aberrant activation of phosphorylated form of glycogen synthase kinase-3β[pS9 GSK-3β(Serine 9 phosphorylation)] is known to trigger Wnt/β-catenin signal cascade but its clinicohistopathological implications in bladder carcinogenesis remain unknown.AIM To investigate the diagnostic and prognostic relevance of expressions of pS9 GSK-3β, β-catenin and its target genes in the pathobiology of bladder cancer.METHODS Bladder tumor tissues from ninety patients were analyzed for quantitative expression and cellular localization of pS9 GSK-3β by immunohistochemical(IHC) staining. 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. Clinicohistopathological variables were obtained from histology reports, follow up and OPD visits of patients.Expressions of the markers were statistically correlated with these variables to determine their significance in clinical setting. Results were analysed using SPSS20.0 software.RESULTS Aberrant(low or no membranous/high nuclear/high cytoplasmic) expression of pS9 GSK-3β was noted in 51% patients and found to be significantly associated with tumor stage and tumor grade(P = 0.01 and 0.04; Mann Whitney U test).Thirty one percent tumors exhibited aberrant co-expression of pS9 GSK-3β andβ–catenin proteins and showed strong statistical association with tumor stage,tumor type, smoking/tobacco chewing status(P = 0.01, 0.02 and 0.04, MannWhitney U test) and shorter overall survival probabilities of patients(P = 0.02;Kaplan Meier test). Nuclear immunostaining of Cyclin D1 in tumors with altered pS9 GSK-3β/β–catenin showed relevance with tumor stage, grade and type.CONCLUSIONβ–catenin and pS9 GSK-3β proteins are identified as markers of diagnostic/prognostic significance in disease pathogenesis. Observed histopathological association of Cyclin D1 identifies it as marker of potential relevance in tumors with altered pS9 GSK-3β/β-catenin.

关 键 词：PATHOBIOLOGY Target genes Tumor stage and grade Wnt/β–catenin signal cascade UROTHELIAL carcinoma of BLADDER 

分 类 号：R737.14[医药卫生—肿瘤]