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.
Highlights
Bladder cancer is one of the most common tumors in human urinary systems, and its incidence lies in the forefront of the global cancer spectrum
The main goal of our work aimed to find the molecular clues for understanding the relationship between the overall survival time of bladder cancer patients and their pathological staging
Through large-scale Cox regression models (i.e., we identified 1078 survival-related genes according univariate and multivariate Cox regression), we identified 1078 survival-related genes according to to their impact on the survival status of 404 bladder cancer patients obtained from The Cancer Genome Atlas (TCGA)
Summary
Bladder cancer is one of the most common tumors in human urinary systems, and its incidence lies in the forefront of the global cancer spectrum. The etiology of bladder cancer has been shown to be multifactorial and complicated, smoking and occupational exposure to chemical carcinogens are considered the main cancer-inducing factors [1]. The elucidation of the underlying molecular mechanisms of tumor evolution is one of the most important questions in cancer biology. The recent advent of high-throughput DNA sequencing has enabled researchers to profile the genomic features in the dysregulation of gene expression under various biological/clinical conditions. It has been revealed that copy number variations (CNVs) can act as an important driving force in several cancers; such genomic variations can alter gene expression, and affect the corresponding biological functions [3]. DNA methylation, an essential epigenetic mechanism, can regulate gene expression by modifying the CpG sites in DNA promoter
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