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Comparative protein-protein interaction network analysis of urothelial carcinoma subtypes

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Abstract:
Background: Cancer, the second leading cause of death in the United States, is a complex disease where multiple genes contribute to the development of the disease (American Cancer Society, 2021). At present, there is a lack of information about the genetic architecture of papillary bladder cancer compared to that of non-papillary bladder cancer. We are investigating the existence of a network of genes in the papillary subtype of urothelial carcinoma that differs from a network of genes in non-papillary urothelial carcinoma. Methods: We obtained data from cBioPortal (Cerami et.al, Gao et.al.), a database containing information from genome sequencing of individuals diagnosed with various types of cancer and their phenotypic data. The dataset obtained from cBioPortal contained the mRNA z-score and RNA-seq data from 408 patients (Robertson, A.G. et.al.). From this dataset, we compared the transcriptome data from two groups: patients with papillary urothelial carcinoma (n=133) and patients with flat carcinoma or carcinoma in situ (non-papillary, n=273). Each patient is a datapoint that contains a list of the most highly expressed genes. To compare the two groups, we employed Protenarium, a multi-sample protein-protein interaction (PPI) tool used to identify clusters of samples with shared networks (Armanious, D et.al.). This tool can be used to analyze the PPI networks of patients and visualize them in clusters based on their network similarities from any genomic data from high throughput screening methods including Next Generation Sequencing (NGS). We hypothesized that we would observe distinct networks and pathways for the papillary and non-papillary groups, suggesting that there are different cellular mechanisms behind papillary and non-papillary bladder cancer types that present unique therapeutic targets or genomic screening markers. Results: The resulting PPI networks contained genes unique to the bladder cancer subtype, with genes involved in the MAPK pathway unique to the papillary cancer network and genes involved in the estrogen signaling pathway unique to the non-papillary cancer network. This is a unique approach to investigate these datasets from the network biology perspectives where we take into consideration each patients’ exclusive PPI network that reflect the potential consensus networks as in clusters for the disease phenotype.

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Citation

Chou, Charissa, Uzun, Alper, and Uzun, Ece Gamsiz, "Comparative protein-protein interaction network analysis of urothelial carcinoma subtypes" (2021). Summer Research Symposium. Brown Digital Repository. Brown University Library. https://doi.org/10.26300/47k4-xr40

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  • Summer Research Symposium

    Each year, Brown University showcases the research of its undergraduates at the Summer Research Symposium. More than half of the student-researchers are UTRA recipients, while others receive funding from a variety of Brown-administered and national programs and fellowships and go …
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