BACKGROUND: Combination @entity902 chemotherapy is standard first-line therapy for metastatic @entity189 (mUC). Defining the @entity902 response biomarkers for @entity1 with mUC could establish personalize medicine and provide insights into mUC biology. Although DNA repair mechanisms have been hypothesized to mediate the @entity902 response, we sought to analyze whether increased expression of DNA damage genes would correlate with worse @entity1349 ( @entity1349 ) in @entity1 with mUC. @entity1 AND METHODS: We retrospectively identified a clinically annotated cohort of @entity1 with mUC, who had been treated with first-line @entity902 combination chemotherapy. A tissue microarray was constructed from @entity406 -fixed @entity982 -embedded tissue from the @entity5 before treatment. Immunohistochemical analysis of the following DNA repair proteins was performed: @entity11833 , @entity6545 , @entity6069 , PAR, and @entity12982 . Nuclear and cytoplasmic expression was analyzed using multispectral imaging. Nuclear staining was used for the survival analysis. Cox regression analysis was used to evaluate the associations between the percentage of positive nuclear staining and @entity1349 in multivariable analysis, controlling for known prognostic variables. RESULTS: In a cohort of 104 @entity1 with mUC, a greater percentage of nuclear staining of @entity11833 (hazard ratio [HR], 2.7; 95% confidence interval [CI], 1.5-4.9; P  = .0007), @entity6545 (HR, 5.6; 95% CI, 1.7-18.3; P  = .005), and PAR (HR, 2.2; 95% CI, 1.1-4.4; P  = .026) was associated with worse @entity1349 . @entity5345 , @entity2674 , and @entity12982 expression was not associated with @entity1349 (P  = .76, P  = .38, and P  = .09, respectively). A greater percentage of combined @entity11833 and @entity6545 nuclear staining was strongly associated with worse @entity1349 (P  = .005). CONCLUSION: A high percentage of nuclear staining of @entity11833 , @entity6545 , and PAR, assessed by immunohistochemistry, correlated with worse @entity1349 for @entity1 with mUC treated with first-line @entity902 combination chemotherapy, supporting the evidence of the DNA repair pathways' role in the prognosis of mUC. We also report new evidence that @entity6545 and PAR might play a role in the @entity902 response. Additional prospective studies are required to determine the prognostic or predictive nature of these biomarkers in mUC.

Expression Levels of DNA Damage Repair Proteins Are Associated With Overall Survival in XXXX -Treated Advanced @entity189 .

@entity1 :: ('9606', 'Species') :: ['patients', 'PATIENTS'] @entity11833 :: ('2067', 'Gene') :: ['ERCC1'] @entity5 :: ('MESH:D009369', 'Disease') :: ['primary tumor'] @entity5345 :: ('672', 'Gene') :: ['BRCA1'] @entity2674 :: ('675', 'Gene') :: ['BRCA2'] @entity406 :: ('MESH:D005557', 'Chemical') :: ['formalin'] @entity189 :: ('MESH:D002277', 'Disease') :: ['urothelial carcinoma'] @entity12982 :: ('142', 'Gene') :: ['PARP-1'] @entity6069 :: ('672;675', 'Gene') :: ['BRCA1/2'] @entity982 :: ('MESH:D010232', 'Chemical') :: ['paraffin'] @entity6545 :: ('5888', 'Gene') :: ['RAD51'] @entity902 :: ('MESH:D010984', 'Chemical') :: ['platinum'] @entity1349 :: ('MESH:D011475', 'Disease') :: ['OS', 'overall survival']
@entity902 :: (MESH:D010984,Chemical) :: ['Platinum']
