期刊
BIOMOLECULES
卷 10, 期 10, 页码 -出版社
MDPI
DOI: 10.3390/biom10101377
关键词
cholangiocarcinoma; genomic alterations; omics; metabolites; small molecule compounds; drugs
资金
- Academia Sinica
- Ministry of Science and Technology [AS-SUMMIT-108, AS-SUMMIT-109, ASKPQ-109-BioMed, MOST-108-3114-Y-001-002, MOST 107-2320-B-001 -016 -MY3]
- Chang Gung Memorial Hospital [CORPG3J0251similar to2, CMRPG3I0241similar to2, CRRPG3K0011, CRRPG3K0031, CMRPG3K0711]
Cholangiocarcinoma (CCA) has been identified as a highly malignant cancer that can be transformed from epithelial cells of the bile duct, including intrahepatic, perihilar and extrahepatic. High-resolution imaging tools (abdominal ultrasound, computed tomography and percutaneous transhepatic cholangial drainage) are recruited for diagnosis. However, the lack of early diagnostic biomarkers and treatment evaluation can lead to serious outcomes and poor prognosis (i.e., CA19-9, MUC5AC). In recent years, scientists have established a large number of omics profiles to reveal underlying mechanisms and networks (i.e., IL-6/STAT3, NOTCH). With these results, we achieved several genomic alteration events (i.e., TP53(mut,) KRAS(mut)) and epigenetic modifications (i.e., DNA methylation, histone modification) in CCA cells and clinical patients. Moreover, we reviewed candidate gene (such as NF-kB, YAP1) that drive gene transcription factors and canonical pathways through transcriptomics profiles (including microarrays and next-generation sequencing). In addition, the proteomics database also indicates which molecules and their directly binding status could trigger dysfunction signatures in tumorigenesis (carbohydrate antigen 19-9, mucins). Most importantly, we collected metabolomics datasets and pivotal metabolites. These results reflect the pharmacotherapeutic options and evaluate pharmacokinetic/pharmacodynamics in vitro and in vivo. We reversed the panels and selected many potentially small compounds from the connectivity map and L1000CDS(2) system. In this paper, we summarize the prognostic value of each candidate gene and correlate this information with clinical events in CCA. This review can serve as a reference for further research to clearly investigate the complex characteristics of CCA, which may lead to better prognosis, drug repurposing and treatment strategies.
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