Gasdermin D: A potential mediator and prognostic marker of bladder cancer

Background: Bladder cancer is considered one of the commonest widespread cancers, its presentation ranges from non-muscle invasive form to being muscle-invasive. The gasdermin family of proteins consists of six proteins. Members of gasdermin family are involved in pyroptosis; which is considered as...

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Main Authors: Randa El-Gamal, Mona Abdelrahim, Mohamed El-Sherbiny, Eman T. Enan, Mohammad El-Nablaway
Format: Article
Language:English
Published: Frontiers Media S.A. 2022-09-01
Series:Frontiers in Molecular Biosciences
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fmolb.2022.972087/full
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author Randa El-Gamal
Randa El-Gamal
Mona Abdelrahim
Mohamed El-Sherbiny
Eman T. Enan
Mohammad El-Nablaway
Mohammad El-Nablaway
author_facet Randa El-Gamal
Randa El-Gamal
Mona Abdelrahim
Mohamed El-Sherbiny
Eman T. Enan
Mohammad El-Nablaway
Mohammad El-Nablaway
author_sort Randa El-Gamal
collection DOAJ
description Background: Bladder cancer is considered one of the commonest widespread cancers, its presentation ranges from non-muscle invasive form to being muscle-invasive. The gasdermin family of proteins consists of six proteins. Members of gasdermin family are involved in pyroptosis; which is considered as type of inflammatory apoptosis via participation of gasdermin D and inflammatory caspases.Purpose: The goal of this research was to look into the potential involvement of gasdermin D in pathogenesis of bladder cancer, In addition, to investigate its potential role as a prognostic marker of bladder cancer.Methods: Gasdermin D gene and protein expression was examined in fresh frozen 80 bladder cancer specimens (30 NMIBC, and 50 MIBC) and the matching 80 control tissue samples utilizing real-time polymerase chain reaction and western blotting. Furthermore, the immunoreactivity of gasdermin D protein was also detected by immunohistochemistry.Results: Gasdermin D gene and protein expression showed a highly significant difference between the control and the two bladder cancer groups (p < 0.001), as demonstrated by real-time PCR, western blotting and immunohistochemistry. Cox proportional hazards regression models showed that lower gasdermin D gene expression in cancer patients (≤1.58-fold), and younger age (≤53 years) were linked with a higher risk of local tumor recurrence. Moreover, higher gasdermin D gene expression (>2.18-fold), and lymph nodes’ involvement were associated with an increased mortality.Conclusion: Gasdermin D is involved in the pathogenesis of bladder cancer and muscle invasion, in addition, tissue gasdermin D expression may be used as useful tool to predict local tumor recurrence.
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spelling doaj.art-c91a9e6e20034f25a4a6b20562d22cd82022-12-22T02:15:08ZengFrontiers Media S.A.Frontiers in Molecular Biosciences2296-889X2022-09-01910.3389/fmolb.2022.972087972087Gasdermin D: A potential mediator and prognostic marker of bladder cancerRanda El-Gamal0Randa El-Gamal1Mona Abdelrahim2Mohamed El-Sherbiny3Eman T. Enan4Mohammad El-Nablaway5Mohammad El-Nablaway6Department of Medical Biochemistry, Faculty of Medicine, Mansoura University, Mansoura, EgyptMedical Experimental Research Center (MERC), Faculty of Medicine, Mansoura University, Mansoura, EgyptConsultant of Pathology, Urology and Nephrology Center, Mansoura University, Mansoura, EgyptDepartment of Basic Medical Sciences, Anatomy Unit, College of Medicine, AlMaarefa University, Riyadh, Saudi ArabiaDepartment of Pathology, Faculty of Medicine, Mansoura University, Mansoura, EgyptDepartment of Medical Biochemistry, Faculty of Medicine, Mansoura University, Mansoura, EgyptMedical Biochemistry Unit, Department of Basic Medical Sciences, College of Medicine, Almaarefa University, Riyad, Saudi ArabiaBackground: Bladder cancer is considered one of the commonest widespread cancers, its presentation ranges from non-muscle invasive form to being muscle-invasive. The gasdermin family of proteins consists of six proteins. Members of gasdermin family are involved in pyroptosis; which is considered as type of inflammatory apoptosis via participation of gasdermin D and inflammatory caspases.Purpose: The goal of this research was to look into the potential involvement of gasdermin D in pathogenesis of bladder cancer, In addition, to investigate its potential role as a prognostic marker of bladder cancer.Methods: Gasdermin D gene and protein expression was examined in fresh frozen 80 bladder cancer specimens (30 NMIBC, and 50 MIBC) and the matching 80 control tissue samples utilizing real-time polymerase chain reaction and western blotting. Furthermore, the immunoreactivity of gasdermin D protein was also detected by immunohistochemistry.Results: Gasdermin D gene and protein expression showed a highly significant difference between the control and the two bladder cancer groups (p < 0.001), as demonstrated by real-time PCR, western blotting and immunohistochemistry. Cox proportional hazards regression models showed that lower gasdermin D gene expression in cancer patients (≤1.58-fold), and younger age (≤53 years) were linked with a higher risk of local tumor recurrence. Moreover, higher gasdermin D gene expression (>2.18-fold), and lymph nodes’ involvement were associated with an increased mortality.Conclusion: Gasdermin D is involved in the pathogenesis of bladder cancer and muscle invasion, in addition, tissue gasdermin D expression may be used as useful tool to predict local tumor recurrence.https://www.frontiersin.org/articles/10.3389/fmolb.2022.972087/fullbladder cancergasdermin Dexpressionprognostic markertumor recurrence
spellingShingle Randa El-Gamal
Randa El-Gamal
Mona Abdelrahim
Mohamed El-Sherbiny
Eman T. Enan
Mohammad El-Nablaway
Mohammad El-Nablaway
Gasdermin D: A potential mediator and prognostic marker of bladder cancer
Frontiers in Molecular Biosciences
bladder cancer
gasdermin D
expression
prognostic marker
tumor recurrence
title Gasdermin D: A potential mediator and prognostic marker of bladder cancer
title_full Gasdermin D: A potential mediator and prognostic marker of bladder cancer
title_fullStr Gasdermin D: A potential mediator and prognostic marker of bladder cancer
title_full_unstemmed Gasdermin D: A potential mediator and prognostic marker of bladder cancer
title_short Gasdermin D: A potential mediator and prognostic marker of bladder cancer
title_sort gasdermin d a potential mediator and prognostic marker of bladder cancer
topic bladder cancer
gasdermin D
expression
prognostic marker
tumor recurrence
url https://www.frontiersin.org/articles/10.3389/fmolb.2022.972087/full
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