Cholangiocarcinoma (CC) is a highly lethal malignant tumor that arises from the biliary tract epithelium.
Background:
Cholangiocarcinoma (CC) oncogenesis and development are largely unknown molecular processes. The objective of this study was to map the expression of genes involved in CC oncogenesis and sarcomatous transdifferentiation across the entire genome.
Methods:
DNA microarray technology was used to find the genes that differed in expression between CC cell lines or tissues and cultivated normal biliary epithelial (NBE) cells. Expressions were verified in CC tissues and cells from humans.
Results:
We found a group of 342 genes that are often regulated (>2-fold change) in cell line and tissue samples using unsupervised hierarchical clustering technique. 289 of them, including tumour suppressor genes, were downregulated, while 53 of them, including genes connected to tumours, were elevated (0.5 fold change). Immunohistochemistry was used to confirm the expression of SPP1, EFNB2, E2F2, IRX3, PTTG1, PPAR, KRT17, UCHL1, IGFBP7, and SPARC proteins in human and hamster CC tissues. When sarcomatoid CC cells were compared to three adenocarcinomatous CC cell lines, additional unsupervised hierarchical clustering analysis found 292 differently upregulated genes (>4-fold change) and 267 differentially downregulated genes (0.25 fold change). Immunoblot analysis and immunohistochemistry labelling were used to confirm that 12 proteins were expressed in the CC cell lines. We discovered that during the sarcomatoid transdifferentiation of CC, the methylation-silenced proteins LDHB, BNIP3, UCHL1, and NPTX2 were restored, along with the expression of the proteins linked to the epithelial-mesenchymal transition (EMT), VIM and TWIST1.
In conclusion, identifying molecular targets for cholangiocarcinoma diagnosis and prognosis may be aided by the dysregulation of oncogenes, tumour suppressor genes, and methylation-related genes.
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