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Omics-Based Platforms: Current Status and Potential Use for Cholangiocarcinoma.
Yu-Chan Chang1,2, Ming-Huang Chen3,4, Chun-Nan Yeh5,6
1Department of Biomedical Imaging and Radiological Sciences, National Yang-Ming University, Taipei 112, Taiwan.
Biomolecules
|October 1, 2020
Summary
Cholangiocarcinoma (CCA) research integrates omics data to identify biomarkers and therapeutic targets. This review highlights genomic alterations, epigenetic modifications, and metabolites for improved prognosis and drug repurposing in bile duct cancer.
Area of Science:
- Oncology and Molecular Biology
- Genomics, Epigenetics, Proteomics, and Metabolomics
Background:
- Cholangiocarcinoma (CCA) is a highly malignant bile duct cancer with poor prognosis due to limited early diagnostic biomarkers and treatment evaluation methods.
- Current diagnostic tools lack sensitivity for early detection, and existing biomarkers like CA19-9 and MUC5AC have limitations.
Purpose of the Study:
- To comprehensively review omics profiles (genomics, epigenetics, transcriptomics, proteomics, metabolomics) for understanding CCA mechanisms.
- To identify candidate genes, molecular pathways, and metabolites with prognostic value in CCA.
- To explore potential therapeutic strategies, including drug repurposing, based on integrated omics data.
Main Methods:
- Integration of multi-omics data, including genomic alterations (e.g., TP53mut, KRASmut), epigenetic modifications (DNA methylation, histone modification), and transcriptomics (microarrays, next-generation sequencing).
- Analysis of proteomics data to identify key molecules and their roles in tumorigenesis.
- Collection and analysis of metabolomics datasets to pinpoint pivotal metabolites and evaluate pharmacodynamics/pharmacokinetics.
- Utilizing the Connectivity Map and L1000CDS2 system for small compound selection and drug repurposing.
Main Results:
- Identification of key genomic alterations (e.g., TP53mut, KRASmut) and epigenetic modifications driving CCA.
- Characterization of molecular networks (e.g., IL-6/STAT3, NOTCH) and candidate genes (e.g., NF-kB, YAP1) involved in CCA pathogenesis.
- Discovery of pivotal metabolites and their association with therapeutic options and treatment evaluation.
- Selection of potential small compounds for therapeutic intervention through data mining.
Conclusions:
- Integrated omics analysis provides a deeper understanding of CCA complexity, revealing prognostic markers and therapeutic targets.
- This review serves as a reference for future research into CCA, potentially leading to improved diagnostic strategies, drug repurposing, and enhanced treatment outcomes.
- The identified molecular signatures and candidate compounds offer promising avenues for developing novel therapeutic strategies for cholangiocarcinoma.
