Potential candidate treatment agents for targeting of cholangiocarcinoma identified by gene expression profile analysis

Abstract

Cholangiocarcinoma (CCA) remains to be a major health problem in several Asian countries including Thailand. The molecular mechanism of CCA is poorly understood. Early diagnosis is difficult, and at present, no effective therapeutic drug is available. The present study aimed to identify the molecular mechanism of CCA by gene expression profile analysis and to search for current approved drugs which may interact with the upregulated genes in CCA. Gene Expression Omnibus (GEO) was used to analyze the gene expression profiles of CCA patients and normal subjects. Using the Kyoto Encyclopedia of Genes and Genomes (KEGG), gene ontology enrichment analysis was also performed, with the KEGG pathway analysis indicating that pancreatic secretion, protein digestion and absorption, fat digestion and absorption, and glycerolipid metabolism may serve important roles in CCA oncogenesis. The drug signature database (DsigDB) was used to search for US Food and Drug Administration (FDA)-approved drugs potentially capable of reversing the effects of the upregulated gene expression in CCA. A total of 61 antineoplastic and 86 non-antineoplastic drugs were identified. Checkpoint kinase 1 was the most interacting with drug signatures. Many of the targeted protein inhibitors that were identified have been approved by the US-FDA as therapeutic agents for non-antineoplastic diseases, including cimetidine, valproic acid and lovastatin. The current study demonstrated an application for bioinformatics analysis in assessing the potential efficacy of currently approved drugs for novel use. The present results suggest novel indications regarding existing drugs useful for CCA treatment. However, further in vitro and in vivo studies are required to support the current predictions.

Cellular expression profiles of Epstein-Barr virus-transformed B-lymphoblastoid cell lines

“…A study of liver hepatocellular carcinoma (HCC) reported high levels of BIRC5 expression in HCC compared with the present study, which reported the downregulation of BIRC5 in EBV-transformed BLCL (41). TROAP was found to be upregulated in cholangiocarcinoma (42); however, the present study reported a downregulation of TROAP expression in EBV-transformed BLCL. These findings indicate that each pathogen has an independent ability to alter cellular gene expression that transforms normal cells into immortalized cells and causes cancer progression.…”

Suppressive effects of umbilical cord mesenchymal stem cell-derived exosomal miR-15a-5p on the progression of cholangiocarcinoma by inhibiting CHEK1 expression

“…As displayed in Table S1 , CHEK1 was the most significant upregulated gene. A published research has shown that CHEK1 is an important factor related to DNA replication and cell survival in cancer cells [ 21 ], and executes the function of the biological regulating enzyme in CCA [ 22 ]. The expression data of CHEK1 were further extracted from the CCA-related microarray data GSE45001 and GSE77984 and box plots were drawn.…”

A2M is a potential core gene in intrahepatic cholangiocarcinoma

“…The determination of the molecular mechanism about tumorigenesis is very important for the diagnosis and treatment of cancer patients [ 24 ]. There is an urgent need to study the pathogenesis of intrahepatic cholangiocarcinoma and the knowledge gained may help us to develop new clinical treatment strategies [ 25 ].…”