scholarly journals Proteomics analysis in urinary bladder cancer patients identifies urinary SOD2 as a predictive marker of recurrence

Author(s):  
Nitu Kumari ◽  
Subasa Chandra Biswal ◽  
Shweta Chaudhary ◽  
Deepankar Malalkar ◽  
Uma S Dubey ◽  
...  

Early non-invasive detection of tumor is an urgent clinical need for managing urothelial bladder cancer. Cystoscopy and cytology are the current standards for diagnosis of recurrence, but are limited by low sensitivity. Quantitative proteomics tool was employed to identify important deregulated molecules in bladder cancer tissues and validated using Western blot and immunohistochemistry analysis. A set of 1137 proteins were identified in four paired bladder cancer patients. Among these, 64 proteins were deregulated in all cases among which 9 were commonly up-regulated. The Ingenuity Pathway Analysis (IPA) generated top 11 Networks in which three commonly upregulated (SERPING1, SOD2 and HSPB6) proteins were involved and selected for further validation. Tissue expression of SOD2, SERPING1 and HSPB6 monitored in an independent sample set (n=18) by immuno-histochemical analysis showed similar profile. Western blot analysis of these proteins in urine of bladder cancer (n=26) and healthy subjects (n=10) showed a specificity and sensitivity of >80% for SOD2 and selected for further validation in a separate set (n=150) by ELISA. Significant elevation in urinary SOD2 level was found in urothelial bladder cancer patients compared to healthy controls and in recurrent cases compared to primary (p-value<0.001). Kaplan Meier survival analysis showed urinary SOD2 concentration >2,100 pg/ml was significantly associated with poorer survival and cumulative survival of patient with low SOD2 concentration was 34.4% compared to 18.9% in patient with high SOD2 at 24 months (p=0.025). The study identifies SOD2 as a non-invasive biomarker which may help to extend the period between cystoscopies during follow-up.

2019 ◽  
Vol 20 (6) ◽  
pp. 1291 ◽  
Author(s):  
Aikaterini Giannopoulou ◽  
Athanassios Velentzas ◽  
Eumorphia Konstantakou ◽  
Margaritis Avgeris ◽  
Stamatia Katarachia ◽  
...  

Urinary bladder cancer is a common malignancy, being characterized by substantial patient mortality and management cost. Its high somatic-mutation frequency and molecular heterogeneity usually renders tumors refractory to the applied regimens. Hitherto, methotrexate-vinblastine-adriamycin-cisplatin and gemcitabine-cisplatin represent the backbone of systemic chemotherapy. However, despite the initial chemosensitivity, the majority of treated patients will eventually develop chemoresistance, which severely reduces their survival expectancy. Since chromatin regulation genes are more frequently mutated in muscle-invasive bladder cancer, as compared to other epithelial tumors, targeted therapies against chromatin aberrations in chemoresistant clones may prove beneficial for the disease. “Acetyl-chromatin” homeostasis is regulated by the opposing functions of histone acetyltransferases (HATs) and histone deacetylases (HDACs). The HDAC/SIRT (super-)family contains 18 members, which are divided in five classes, with each family member being differentially expressed in normal urinary bladder tissues. Since a strong association between irregular HDAC expression/activity and tumorigenesis has been previously demonstrated, we herein attempt to review the accumulated published evidences that implicate HDACs/SIRTs as critical regulators in urothelial bladder cancer. Moreover, the most extensively investigated HDAC inhibitors (HDACis) are also analyzed, and the respective clinical trials are also described. Interestingly, it seems that HDACis should be preferably used in drug-combination therapeutic schemes, including radiation.


2019 ◽  
Vol 124 (3) ◽  
pp. 361-362
Author(s):  
Rohit K. Jain ◽  
Petros Grivas ◽  
Sumanta K. Pal

2012 ◽  
Vol 11 (1) ◽  
pp. e905-e905a
Author(s):  
P.J. Bostrom ◽  
J. Thoms ◽  
B.W.G. Van Rhijn ◽  
O. Ahmed ◽  
O. Stakhovskyi ◽  
...  

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