Dataset Information

Bladder cancer-associated gene expression signatures identified by profiling of exfoliated urothelia.

ABSTRACT: Bladder cancer is the fifth most commonly diagnosed malignancy in the United States and one of the most prevalent worldwide. It harbors a probability of recurrence of >50%; thus, rigorous, long-term surveillance of patients is advocated. Flexible cystoscopy coupled with voided urine cytology is the primary diagnostic approach, but cystoscopy is an uncomfortable, invasive procedure and the sensitivity of voided urine cytology is poor in all but high-grade tumors. Thus, improvements in noninvasive urinalysis assessment strategies would benefit patients. We applied gene expression microarray analysis to exfoliated urothelia recovered from bladder washes obtained prospectively from 46 patients with subsequently confirmed presence or absence of bladder cancer. Data from microarrays containing 56,000 targets was subjected to a panel of statistical analyses to identify bladder cancer-associated gene signatures. Hierarchical clustering and supervised learning algorithms were used to classify samples on the basis of tumor burden. A differentially expressed geneset of 319 gene probes was associated with the presence of bladder cancer (P < 0.01), and visualization of protein interaction networks revealed vascular endothelial growth factor and angiotensinogen as pivotal factors in tumor cells. Supervised machine learning and a cross-validation approach were used to build a 14-gene molecular classifier that was able to classify patients with and without bladder cancer with an overall accuracy of 76%. Our results show that it is possible to achieve the detection of bladder cancer using molecular signatures present in exfoliated tumor urothelia. Further investigation and validation of the cancer-associated profiles may reveal important biomarkers for the noninvasive detection and surveillance of bladder cancer.

SUBMITTER: Rosser CJ

PROVIDER: S-EPMC2729268 | biostudies-literature | 2009 Feb

REPOSITORIES: biostudies-literature

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Bladder cancer-associated gene expression signatures identified by profiling of exfoliated urothelia.

Rosser Charles J CJ Liu Li L Sun Yijun Y Villicana Patrick P McCullers Molly M Porvasnik Stacy S Young Paul R PR Parker Alexander S AS Goodison Steve S

Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology 20090203 2

Bladder cancer is the fifth most commonly diagnosed malignancy in the United States and one of the most prevalent worldwide. It harbors a probability of recurrence of >50%; thus, rigorous, long-term surveillance of patients is advocated. Flexible cystoscopy coupled with voided urine cytology is the primary diagnostic approach, but cystoscopy is an uncomfortable, invasive procedure and the sensitivity of voided urine cytology is poor in all but high-grade tumors. Thus, improvements in noninvasive ...[more]

PMID: 19190164

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Project description:BackgroundBladder carcinoma (BLCA) is a common malignant tumor with high morbidity and mortality in the urinary system. Pyroptosis is a pattern of programmed cell death that is closely associated with progression of tumors. Therefore, it is significant to probe the expression of pyroptosis-related genes (PRGs) in BLCA.MethodsThe differentially expressed genes in normal and BLCA tissues were first obtained from the Cancer Genome Atlas (TCGA) database analysis, as well as PRGs from the National Center for Biotechnology Information (NCBI) database, intersecting to obtain differentially expressed pyroptosis-related genes (DEPRGs) in BLCA. With the construction of a prognostic model of pyroptosis by regression analysis, we derived and validated key genes, which were ascertained as a separate prognostic marker by individual prognostic and clinical relevance analysis. In addition, we gained six immune cells from the Tumor Immune Evaluation Resource (TIMER) website and analyzed the relationship between pyroptosis prognostic genes and immune infiltration.ResultOur results revealed that 31 DEPRGs were available by comparing normal and BLCA tissues with |log2 (fold change, FC)| > 0.5 and FDR <0.05. Four key genes (CRTAC1, GSDMB, AIM2, and FOXO3) derived from the pyroptosis prognostic model were experimentally validated for consistent expression in BLCA patients. Following risk scoring, the low-risk group of BLCA patients had noticeably higher overall survival (OS) than the high-risk group (p < 0.001). Risk score was still an independent prognostic factor (HR = 1.728, 95% CI =1.289-2.315, p < 0.001). In addition, we found remarkable correlations among the expression of pyroptosis-related prognostic genes and the immune infiltration of CD4+ T cells, CD8+ T cells, B cells, dendritic cells, macrophages, and neutrophils.ConclusionGenes (CRTAC1, GSDMB, AIM2, and FOXO3) associated with pyroptosis are potential BLCA prognostic biomarkers that act as an essential part in the predictive prognosis of survival and immunotherapy of BLCA.

Dataset Information

Bladder cancer-associated gene expression signatures identified by profiling of exfoliated urothelia.

Publications

Bladder cancer-associated gene expression signatures identified by profiling of exfoliated urothelia.

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