Association of SNPs in the PAI1 Gene with Disease Recurrence and Clinical Outcome in Bladder Cancer
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PROVIDER: PRJNA930502 | ENA |
REPOSITORIES: ENA
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Project description:Bladder cancer is one of the most common cancer types worldwide and is characterized by a high rate of recurrence. Previous studies have demonstrated that plasminogen activator inhibi-tor-1 (PAI1) plays an important role in bladder cancer development. The aim of our retrospective study was to assess the effects of PAI1 mutational status in bladder tumors. In this study, we evaluated the mutational status of PAI1 in a series of independent cohorts, comprised of a total of 660 subjects. We identified two clinically relevant 3’ untranslated region (UTR) single nucleotide polymorphisms (SNPs) in PAI1. Caucasian patients with at least one of the SNPs had high risk of recurrence and shorter survival. Additional studies using cell lines demonstrated that one SNP increased the anti-apoptotic effect of PAI1, and another lose the control of cancer cellular growth. This study underscores the relevance and influence of these SNPs in bladder cancer.
2024-01-29 | GSE224309 | GEO
Project description:Expression profiling of superficial bladder tumours to delineate the expression pattern differences between non-recurring and recurring tumours. Keywords = bladder cancer, superficial, recurrence, prediction Keywords: other
2002-12-08 | GSE88 | GEO
Project description:Although non muscle-invasive bladder cancer can be treated successfully by surgical resection, there is a high rate of recurrence, which frequently develops into an invasive form of cancer. Due to the lack of marker molecules to predict recurrence, it is currently recommended that after resection each patient is screened via cystoscopy at least twice a year. This results in a psychic burden to the patient and substantial economic costs to the health care system. Using antibody microarrays targeting 724 different cancer-related proteins, we studied protein profiles of patients with and without recurrence. The analysis revealed 255 proteins of differential abundance. Most are involved in the regulation and execution of apoptosis and cell proliferation. For prognosis, a signature of 20 proteins was determined that predicts bladder cancer recurrence with 100% sensitivity and 80% specificity. As a measure of overall accuracy, the area under the curve (AUC) value was found to be 90%. This is well within a clinically relevant window of quality and should support decision making about the stringency of surveillance or even different treatment options.
2014-04-07 | E-MEXP-3625 | biostudies-arrayexpress
Project description:PurposeBladder cancer (BCa) is one of the most common cancer types worldwide and is characterized by a high rate of recurrence. In previous studies, we and others have described the functional influence of plasminogen activator inhibitor-1 (PAI1) in bladder cancer development. While polymorphisms in PAI1 have been associated with increased risk and worsened prognosis in some cancers, the mutational status of PAI1 in human bladder tumors has not been well defined.MethodsIn this study, we evaluated the mutational status of PAI1 in a series of independent cohorts, comprised of a total of 660 subjects.ResultsSequencing analyses identified two clinically relevant 3' untranslated region (UTR) single nucleotide polymorphisms (SNPs) in PAI1 (rs7242; rs1050813). Somatic SNP rs7242 was present in human BCa cohorts (overall incidence of 72%; 62% in Caucasians and 72% in Asians). In contrast, the overall incidence of germline SNP rs1050813 was 18% (39% in Caucasians and 6% in Asians). Furthermore, Caucasian patients with at least one of the described SNPs had worse recurrence-free survival and overall survival (p = 0.03 and p = 0.03, respectively). In vitro functional studies demonstrated that SNP rs7242 increased the anti-apoptotic effect of PAI1, and SNP rs1050813 was related to a loss of contact inhibition associated with cellular proliferation when compared to wild type.ConclusionFurther investigation of the prevalence and potential downstream influence of these SNPs in bladder cancer is warranted.
| S-EPMC10003630 | biostudies-literature
Project description:Bladder carcinoma (BLCA) is characterized by a high rate of post-surgery relapse and multifocality, with multifocal tumors carrying a 40% higher risk of recurrence compared to single tumors. Recurrence is a major contributor to bladder cancer-specific mortality. However, understanding interregional or intraregional malignant heterogeneity and cellular communication within the primary and recurrence tumor microenvironment (TME) remains a significant challenge. Here, we employed single-cell RNA sequencing (scRNA-seq) to analyze separate tumor lesions from five multifocal bladder cancer patients (comprising three primary tumors and two recurrence tumors).
2024-11-15 | GSE277524 | GEO
Project description:ApoC-III is a proatherogenic protein associated with elevated triglycerides; its deficiency is associated with reduced atherosclerosis. Mixed dyslipidemia, characterized by elevated triglyceride and apoC-III levels and low HDL cholesterol level, with or without elevated LDL cholesterol, increases cardiovascular disease risk and is commonly treated with combined statin and fibrate therapy. We sought to identify single nucleotide polymorphisms (SNPs) associated with apoC-III level response to combination therapy with statins and fenofibric acid (FA) in individuals with mixed dyslipidemia. Participants in a multicenter, randomized, double-blind, active-controlled study examining response to FA alone and in combination with statin were genotyped for candidate SNPs. Association between genotyed SNPs and APOC3 response to therapy was conducted We sought to identify single nucleotide polymorphisms (SNPs) associated with apoC-III level response to combination therapy with statins and fenofibric acid (FA) in individuals with mixed dyslipidemia. Participants in a multicenter, randomized, double-blind, active-controlled study examining response to FA alone and in combination with statin were genotyped for candidate SNPs. Genomic DNA extracted from peripheral blood was genotyped using a custom GoldenGate bead array encompassing 384 SNPs (Illumina). Multivariate linear regression and 2-way ANOVA for percent change in apoC-III level were performed between the groups receiving FA alone compared with FA+statin compared with statin alone.
2012-01-11 | E-GEOD-34945 | biostudies-arrayexpress
Project description:ApoC-III is a proatherogenic protein associated with elevated triglycerides; its deficiency is associated with reduced atherosclerosis. Mixed dyslipidemia, characterized by elevated triglyceride and apoC-III levels and low HDL cholesterol level, with or without elevated LDL cholesterol, increases cardiovascular disease risk and is commonly treated with combined statin and fibrate therapy. We sought to identify single nucleotide polymorphisms (SNPs) associated with apoC-III level response to combination therapy with statins and fenofibric acid (FA) in individuals with mixed dyslipidemia. Participants in a multicenter, randomized, double-blind, active-controlled study examining response to FA alone and in combination with statin were genotyped for candidate SNPs. Association between genotyed SNPs and APOC3 response to therapy was conducted
2012-01-11 | GSE34945 | GEO
Project description:At diagnosis approximately 75% of bladder urothelial carcinomas are non muscle invasive bladder cancers (Ta, T1 and Tis), 20% are muscle invasive bladder cancer (T2-T4) and 5% are already metastatic. Non muscle invasive bladder cancers are characterized by tumor recurrence in 60% to 85% of cases and, therefore, long-term followup is needed. The current standard methods to detect and monitor bladder cancer are cystoscopy and cytology. Cystoscopy is an invasive method and cytology is hampered by low sensitivity, especially for low grade tumors. So there is need to develop reliable and noninvasive methods to detect and predict bladder cancer biological behavior. So we have performed high density oligonucleotide microarray for discovery of new molecular markers to diagnose and predict the outcome of bladder cancer. Under an ethical guideline of Chhatrapati Shahuji Maharaj Medical University, India histologically confirmed seven bladder cancer patients were recruited from Department of Urology, Chhatrapati Shahuji Maharaj Medical University, Lucknow, India. Total RNA was extracted from tumor biopsies and hybridized on affymetrix Human Gene ST 1.1 array to determine differentially expressed genes in urinary bladder cancer with muscle invasion in comparison of normal human urinary bladder.
2012-02-22 | E-GEOD-23732 | biostudies-arrayexpress
Project description:At diagnosis approximately 75% of bladder urothelial carcinomas are non muscle invasive bladder cancers (Ta, T1 and Tis), 20% are muscle invasive bladder cancer (T2-T4) and 5% are already metastatic. Non muscle invasive bladder cancers are characterized by tumor recurrence in 60% to 85% of cases and, therefore, long-term followup is needed. The current standard methods to detect and monitor bladder cancer are cystoscopy and cytology. Cystoscopy is an invasive method and cytology is hampered by low sensitivity, especially for low grade tumors. So there is need to develop reliable and noninvasive methods to detect and predict bladder cancer biological behavior. So we have performed high density oligonucleotide microarray for discovery of new molecular markers to diagnose and predict the outcome of bladder cancer.
2012-02-22 | GSE23732 | GEO
Project description:Background Clinically useful molecular markers predicting the clinical course of patients diagnosed with non-muscle invasive bladder cancer are needed to improve treatment outcome. Methods We used custom designed oligonucleotide microarrays to validate four previously reported gene expression signatures for molecular diagnosis of disease stage and carcinoma in situ, and for predicting disease recurrence and progression. We analyzed tumors from 404 patients diagnosed with bladder cancer in hospitals in Denmark, Sweden, England, Spain and France. Molecular classifications were compared to pathological diagnosis and clinical outcome. The median follow-up time for the patients was 3.5 years. Results Classification of disease stage using a 52-gene classifier was found to be highly significantly correlated with pathological stage (P<0.001). Furthermore, the classifier added information regarding future disease progression of Ta or T1 tumors (P<0.001). The molecular 77-gene progression classifier was highly significantly correlated with progression free survival (P<0.001) and cancer specific survival (P=0.001). Furthermore, multivariate Cox´s regression analysis showed the progression classifier to be an independently significant variable associated with disease progression after adjustment for age, sex, stage, grade and treatment (hazard ratio 2.4, P=0.005). The diagnosis of carcinoma in situ (CIS) using a 68-gene classifier showed a highly significant correlation with histopathological CIS diagnosis (odds ratio 5.8, P<0.001) in multivariate logistic regression analysis. Conclusions We conclude that this multicenter validation study confirms the clinical utility of molecular classifiers to guide treatment decisions for patients initially diagnosed with non-muscle invasive bladder cancer. Keywords: Multi center validation study of gene expression signatures
2007-06-15 | GSE5479 | GEO