Dataset Information

Integrative Analysis of Genomic and Clinical Data Reveals Intrinsic Characteristics of Bladder Urothelial Carcinoma Progression.

ABSTRACT: The progression of bladder cancer is generally a complex and dynamic process, involving a variety of biological factors. Here, we aimed to identify a set of survival-related genes that play an important role in the progression of bladder cancer and uncover their synergistic patterns. Based on the large-scale genomic profiling data and clinical information of 404 bladder cancer patients derived from The Cancer Genome Atlas (TCGA) database, we first discovered 1078 survival-related genes related to their survival states using univariate and multivariate Cox proportional hazardous regression. We then investigated the dynamic changes of the cooperative behaviors of these 1078 genes by analyzing their respective genomic features, including copy number variations, DNA methylations, somatic mutations, and microRNA regulatory networks. Our analyses showed that during the progression of bladder cancer, the biological disorder involving the identified survival-related genes can be reflected by multiple levels of abnormal gene regulation, ranging from genomic alteration to post-transcriptional dysregulation. In particular, the stage-specific co-expression networks of these genes undergo a series of structural variations. Our findings provide useful hints on understanding the underlying complex molecular mechanisms related to the evolution of bladder cancer and offer a new perspective on clinical diagnosis and treatment of bladder cancer.

SUBMITTER: Zhou B

PROVIDER: S-EPMC6628253 | biostudies-literature | 2019 Jun

REPOSITORIES: biostudies-literature

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Integrative Analysis of Genomic and Clinical Data Reveals Intrinsic Characteristics of Bladder Urothelial Carcinoma Progression.

Zhou Bin B Guo Rui R

Genes 20190617 6

The progression of bladder cancer is generally a complex and dynamic process, involving a variety of biological factors. Here, we aimed to identify a set of survival-related genes that play an important role in the progression of bladder cancer and uncover their synergistic patterns. Based on the large-scale genomic profiling data and clinical information of 404 bladder cancer patients derived from The Cancer Genome Atlas (TCGA) database, we first discovered 1078 survival-related genes related t ...[more]

PMID: 31212967

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Project description:BackgroundDifferent genomic characterization in urothelial carcinoma (UC) by site of origin may imply contrasting therapeutic opportunities and pathogenetic mechanisms. The aim of this study was to investigate whether differences between upper tract UC (UTUC) and UC of the bladder (UCB) result from intrinsic biological diversity.Materials and methodsWe prospectively sequenced 118 tumors and matched blood DNA from Chinese patients with UC using next-generation sequencing techniques, including 45 UTUC and 73 UCB. Two hundred twenty-six patients with UTUC and 350 patients with UCB for The Cancer Genome Atlas were acquired from the cbioportal.ResultsThere were marked disparities in the mutational landscape for UC according to race and site of origin. Signature 22 for exposure to aristolochic acid was only observed in the UTUC cohort. Conversely, signature 6 for defective DNA mismatch repair only existed in the UCB cohort. Compared with UCB, UTUC had higher clonal and subclonal mutation numbers. TP53, PIK3CA, and FGFR3 mutations may be the driver genes for UTUC, whereas for UCB, the driver gene may be BRCA1. Patients with UTUC had lower PD-L1 than those with UCB. There was no significant difference in the number of DDR mutations, copy number variation counts, and tumor mutational burden between UTUC and UCB.ConclusionUTUC and UCB exhibit significant differences in the prevalence of genomic landscape and carcinogenesis. Consequently, molecular subtypes differ according to location, and these results may imply the site-specific management of patients with urothelial carcinoma. Mutational signature may be used as a screening tool to assist clinical differential diagnosis between UTUC and UCB.Implications for practiceThis study's findings lay the foundation for a deeper understanding of distinct molecular mechanisms and similar treatment opportunities between upper tract urothelial carcinoma (UTUC) and urothelial carcinoma of the bladder (UCB) and had important implications for the site-specific management of patients with urothelial carcinoma. A comprehensive understanding of the biology of UTUC and UCB is needed to identify new drug targets in order to improve clinical outcomes.

Dataset Information

Integrative Analysis of Genomic and Clinical Data Reveals Intrinsic Characteristics of Bladder Urothelial Carcinoma Progression.

Publications

Integrative Analysis of Genomic and Clinical Data Reveals Intrinsic Characteristics of Bladder Urothelial Carcinoma Progression.

Similar Datasets

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