Altered expressions of pS9GSK-3β /β-catenin/EMT markers as strong predictors of short survival in subsets of urothelial carcinoma of bladder patients
Background: Inactive glycogen synthase kinase-3β [phosphorylation at Serine 9 (pS9GSK-3β)] is known to regulate nuclear stabilization of β-catenin and activation of Epithelial-to-mesenchymal transition (EMT) inducing molecules. Present study is taken up to examine the prognostic impact of EMT marker...
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| Format: | Article |
| Language: | English |
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Elsevier
2021-10-01
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| Series: | Advances in Cancer Biology - Metastasis |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S266739402100006X |
| _version_ | 1819032739516514304 |
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| author | Maurya N Goel A Singhai A Garg M |
| author_facet | Maurya N Goel A Singhai A Garg M |
| author_sort | Maurya N |
| collection | DOAJ |
| description | Background: Inactive glycogen synthase kinase-3β [phosphorylation at Serine 9 (pS9GSK-3β)] is known to regulate nuclear stabilization of β-catenin and activation of Epithelial-to-mesenchymal transition (EMT) inducing molecules. Present study is taken up to examine the prognostic impact of EMT markers in urothelial tumors with normal and immunoco-aberrantly expressed pS9GSK-3β and β-catenin. Material and methods: Expressions and subcellular localizations of pS9GSK-3β and β-catenin were checked immunohistochemically in 65 NMIBC and 55 MIBC patients. These tumors were later examined for transcriptomic and protein levels of EMT associated molecules followed by their statistical significance with patients' variables. Results: Number of clinicopathological variables exhibited statistical associations with altered EMT markers in non-muscle invasive and muscle invasive tumors with aberrantly immunoco-expressed pS9GSK-3β and β-catenin. Follow up data were collected in 53 NMIBC and 49 MIBC patients over the average timeline of 48 months. Of 25/53 NMIBC and 33/49 MIBC patients with aberrantly immunoco-expressed pS9GSK-3β and β-catenin, molecular anomaly in EMT markers (E−/M+/T+) was noted in 40% NMIBC and 27.3% MIBC patients. NMIBC patients (100%) exhibiting tumor recurrence had at least two molecular abnormalities, whereas 55.5% MIBC succumbed to death and 44.4% MIBC showed tumor progression suggesting that tumor aggressiveness could be linked to severity of abnormal phenotype. Conclusion: Survival analysis demonstrates altered expressions of pS9GSK-3β/β-catenin/EMT as prognostic markers for poor cancer specific survival (p = 0.049) and short overall survival (p = 0.03) probabilities of MIBC patients. Study establishes altered pS9GSK-3β/β-catenin/EMT profile as a sensitive and effective prognostic tool in a subset of bladder tumors. |
| first_indexed | 2024-12-21T07:06:44Z |
| format | Article |
| id | doaj.art-83fcda4b924c46cba80a1eea111fc109 |
| institution | Directory Open Access Journal |
| issn | 2667-3940 |
| language | English |
| last_indexed | 2024-12-21T07:06:44Z |
| publishDate | 2021-10-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Advances in Cancer Biology - Metastasis |
| spelling | doaj.art-83fcda4b924c46cba80a1eea111fc1092022-12-21T19:12:04ZengElsevierAdvances in Cancer Biology - Metastasis2667-39402021-10-012100006Altered expressions of pS9GSK-3β /β-catenin/EMT markers as strong predictors of short survival in subsets of urothelial carcinoma of bladder patientsMaurya N0Goel A1Singhai A2Garg M3Department of Biochemistry, University of Lucknow, Lucknow, 226007, IndiaDepartment of Urology, King George Medical University, Lucknow, 226003, IndiaDepartment of Pathology, King George Medical University, Lucknow, 226003, IndiaDepartment of Biochemistry, University of Lucknow, Lucknow, 226007, India; Corresponding author.;Background: Inactive glycogen synthase kinase-3β [phosphorylation at Serine 9 (pS9GSK-3β)] is known to regulate nuclear stabilization of β-catenin and activation of Epithelial-to-mesenchymal transition (EMT) inducing molecules. Present study is taken up to examine the prognostic impact of EMT markers in urothelial tumors with normal and immunoco-aberrantly expressed pS9GSK-3β and β-catenin. Material and methods: Expressions and subcellular localizations of pS9GSK-3β and β-catenin were checked immunohistochemically in 65 NMIBC and 55 MIBC patients. These tumors were later examined for transcriptomic and protein levels of EMT associated molecules followed by their statistical significance with patients' variables. Results: Number of clinicopathological variables exhibited statistical associations with altered EMT markers in non-muscle invasive and muscle invasive tumors with aberrantly immunoco-expressed pS9GSK-3β and β-catenin. Follow up data were collected in 53 NMIBC and 49 MIBC patients over the average timeline of 48 months. Of 25/53 NMIBC and 33/49 MIBC patients with aberrantly immunoco-expressed pS9GSK-3β and β-catenin, molecular anomaly in EMT markers (E−/M+/T+) was noted in 40% NMIBC and 27.3% MIBC patients. NMIBC patients (100%) exhibiting tumor recurrence had at least two molecular abnormalities, whereas 55.5% MIBC succumbed to death and 44.4% MIBC showed tumor progression suggesting that tumor aggressiveness could be linked to severity of abnormal phenotype. Conclusion: Survival analysis demonstrates altered expressions of pS9GSK-3β/β-catenin/EMT as prognostic markers for poor cancer specific survival (p = 0.049) and short overall survival (p = 0.03) probabilities of MIBC patients. Study establishes altered pS9GSK-3β/β-catenin/EMT profile as a sensitive and effective prognostic tool in a subset of bladder tumors.http://www.sciencedirect.com/science/article/pii/S266739402100006XClinical relevanceMuscle invasive bladder tumorsNon-muscle invasive bladder tumorspS9GSK-3β/β-catenin/EMTSurvival probabilities |
| spellingShingle | Maurya N Goel A Singhai A Garg M Altered expressions of pS9GSK-3β /β-catenin/EMT markers as strong predictors of short survival in subsets of urothelial carcinoma of bladder patients Advances in Cancer Biology - Metastasis Clinical relevance Muscle invasive bladder tumors Non-muscle invasive bladder tumors pS9GSK-3β/β-catenin/EMT Survival probabilities |
| title | Altered expressions of pS9GSK-3β /β-catenin/EMT markers as strong predictors of short survival in subsets of urothelial carcinoma of bladder patients |
| title_full | Altered expressions of pS9GSK-3β /β-catenin/EMT markers as strong predictors of short survival in subsets of urothelial carcinoma of bladder patients |
| title_fullStr | Altered expressions of pS9GSK-3β /β-catenin/EMT markers as strong predictors of short survival in subsets of urothelial carcinoma of bladder patients |
| title_full_unstemmed | Altered expressions of pS9GSK-3β /β-catenin/EMT markers as strong predictors of short survival in subsets of urothelial carcinoma of bladder patients |
| title_short | Altered expressions of pS9GSK-3β /β-catenin/EMT markers as strong predictors of short survival in subsets of urothelial carcinoma of bladder patients |
| title_sort | altered expressions of ps9gsk 3β β catenin emt markers as strong predictors of short survival in subsets of urothelial carcinoma of bladder patients |
| topic | Clinical relevance Muscle invasive bladder tumors Non-muscle invasive bladder tumors pS9GSK-3β/β-catenin/EMT Survival probabilities |
| url | http://www.sciencedirect.com/science/article/pii/S266739402100006X |
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