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Query: UNIPROT:P04637 (
p53
)
77,613
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Cholangiocellular carcinoma
is a relatively rare malignant tumor, originating from cholangiocytes, with poor prognosis and late diagnosis. It is a malignancy with a variable biological etiology, numerous genetic and epigenetic changes. Its incidence in the Czech Republic is about 1.4 per 100,000 people per year. For good prognosis and long-term survival, early diagnosis with surgical treatment is important. In these cases, a 5-year survival rate is about 20-40 %. In the early diagnosis imaging methods and histopathological verification play an essential role, whereas laboratory oncomarkers are not yet sufficiently accurate. The same applies for genetic markers. This leads to the search of new molecular targets and the high effort in the introduction of cytological and molecular-biological methods with high specificity and sensitivity into routine practice. Current early diagnosis is based on the use of efficient imaging methods. The use of genetic testing, and especially knowledge of the molecular basis of this disease, will be of a great benefit. The observation of the association between the genetic pathways, IDH1, RAS-MAPK etc., and genetic mutations of genes, such as
TP53
, KRAS, SMAD4, BRAF, IDH1/2, may be significant. From the molecular point of view, it is also interesting to monitor oncogenic potential in HBV/HCV infection.
...
PMID:Molecular pathology of cholangiocellular carcinomas. 3110 65
Cholangiocarcinoma
(
CCA
) is a primary malignancy, which is often diagnosed as locally advanced or metastatic. Previous studies have revealed genomic characteristics of
CCA
in Western patients, however comprehensive genomic features of
CCA
in Chinese patients have not been well understood. To explore the specific genomic characteristics of Chinese patients with
CCA
, a total of 66 patients with
CCA
, including 44 intrahepatic
CCA
(iCCA) and 22 extrahepatic
CCA
(exCCA) cases, were studied. The most commonly altered genes in CCAs were
TP53
(62.12%, 41/66), KRAS (36.36%, 24/66), SMAD4 (24.24%, 16/66), TERT (21.21%, 14/66), ARID1A (19.70%, 13/66), CDKN2A (19.70%, 13/66), KMT2C (9.09%, 6/66) and RBM10 (9.09%, 6/66), ERBB2 (7.58%, 5/66) and BRAF (7.58%, 5/66). Many gene mutations, including STK11, CCND1 and FGF19, were only found in iCCA. RBM10 mutations were found to be significantly higher in exCCA. The gene mutations of neurofibromin 1, STK11, CCND1 and FBXW7 specifically occurred in males, whereas gene mutations of ERBB2, AXIN2 and CREBBP specifically occurred in females. ERBB2 mutations were significantly associated with the sex of patients with
CCA
. Mutations in PIK3CA, FGFR2 and ZNF750 were significantly associated with the age of patients with
CCA
and TERT mutations were significantly associated with tumor differentiation. Alterations in KMT2C, PBRM1, AXIN2, MAGI2, BRCA2 and SPTA1 were associated with tumor mutational burden. The findings of the present study suggest that targeted sequencing, using next-generation sequencing technology, provides comprehensive and accurate information on genomic alterations, which will provide novel potential biomarkers for the diagnosis of
CCA
and may guide precise therapeutic strategies for Chinese patients with
CCA
.
...
PMID:Comprehensive genomic profile of cholangiocarcinomas in China. 3225 10
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.
...
PMID:Omics-Based Platforms: Current Status and Potential Use for Cholangiocarcinoma. 3299 89
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