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3-D Cell Culture System for Studying Invasion and Evaluating Therapeutics in Bladder Cancer
Published on: September 13, 2018
Protein interactome of muscle invasive bladder cancer
Akshay Bhat1, Andreas Heinzel2, Bernd Mayer2
1Charité-Universitätsmedizin Berlin, Med. Klinik IV, Berlin, Germany; Mosaiques diagnostics GmbH, Hannover, Germany.
Abstract:
Muscle invasive bladder carcinoma is a complex, multifactorial disease caused by disruptions and alterations of several molecular pathways that result in heterogeneous phenotypes and variable disease outcome. Combining this disparate knowledge may offer insights for deciphering relevant molecular processes regarding targeted therapeutic approaches guided by molecular signatures allowing improved phenotype profiling. The aim of the study is to characterize muscle invasive bladder carcinoma on a molecular level by incorporating scientific literature screening and signatures from omics profiling. Public domain omics signatures together with molecular features associated with muscle invasive bladder cancer were derived from literature mining to provide 286 unique protein-coding genes. These were integrated in a protein-interaction network to obtain a molecular functional map of the phenotype. This feature map educated on three novel disease-associated pathways with plausible involvement in bladder cancer, namely Regulation of actin cytoskeleton, Neurotrophin signalling pathway and Endocytosis. Systematic integration approaches allow to study the molecular context of individual features reported as associated with a clinical phenotype and could potentially help to improve the molecular mechanistic description of the disorder.
Insights
This study characterizes muscle invasive bladder carcinoma by integrating molecular data and literature. It identified three novel pathways involved in bladder cancer, aiding in targeted therapy development.
Area of Science:
- Oncology
- Molecular Biology
- Bioinformatics
Background:
- Muscle invasive bladder carcinoma (MIBC) is a complex disease with heterogeneous phenotypes and variable outcomes.
- Understanding the molecular pathways driving MIBC is crucial for developing targeted therapies.
- Current knowledge integration is limited, hindering comprehensive molecular profiling.
Purpose of the Study:
- To molecularly characterize muscle invasive bladder carcinoma.
- To integrate scientific literature and omics data for a deeper understanding of MIBC.
- To identify novel molecular pathways and therapeutic targets in MIBC.
Main Methods:
- Literature screening and omics signature analysis were performed.
- 286 unique protein-coding genes associated with MIBC were identified.
- A protein-interaction network was constructed to create a molecular functional map.
Main Results:
- Three novel disease-associated pathways were identified: Regulation of actin cytoskeleton, Neurotrophin signalling pathway, and Endocytosis.
- These pathways show plausible involvement in bladder cancer development and progression.
- The molecular functional map provides insights into the complex phenotype of MIBC.
Conclusions:
- Systematic integration of molecular data and literature enhances the understanding of MIBC.
- The identified pathways offer potential targets for developing novel, signature-guided therapies for bladder cancer.
- Improved molecular mechanistic descriptions can lead to better phenotype profiling and patient outcomes.
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