Project description:To further understand the molecular mechanisms in the development of gallbladder cancer, we employed this microarray to identify lncRNAs associated with gallbladder cancer.
Project description:To further understand the molecular mechanisms in the development of gallbladder cancer, we employed this microarray to identify lncRNAs associated with gallbladder cancer. 9 pairs of gallbladder cancer tissues and paired normal gallbladder tissues were collected after colecystectomy.
Project description:Gallbladder cancer is a rare but highly malignant cancer. We performed the transcriptional profile sequencing to figure out the potential mechanisms, which might significantly affect gallbladder cancer progression.
Project description:MicroRNAs (miRNAs) play a critical role in the progression of cancer. However, little is known on the miRNAs expression profiles of gallbladder cancer.We performed this microarray to identify miRNAs associated with gallbladder cancer.
Project description:We carried out an iTRAQ-based quantitative proteomic analysis of gallbladder cancer and adjacent non-tumor tissue to systematically identify differentially expressed proteins in gallbladder cancer. Ten gallbladder adenocarcinoma and ten adjacent non-tumor tissue samples were selected post pathological confirmation for the study. Samples were pooled and In-solution trypsin digestion was carried out. Post digestion, peptides were iTRAQ labeled with 114 and 115 (gallbladder adenocarcinoma) and 116 and 117 (adjacent non-tumor samples). LC-MS/MS analysis of SCX fractions was carried out using a reversed phase analytical C18 column connected to 1200 Series Nanoflow LC interfaced with LTQ-Orbitrap Velos. Data were acquired using Xcalibur 2.1. Proteome Discoverer (v 1.3) suite was used for quantitation and database searches. LC-MS/MS data were searched using Mascot and SEQUEST search algorithms against Human RefSeq 50 supplemented with frequently observed contaminants.
Project description:Epigenome-wide methylation levels were measured in patients from Chiel with gallstone disease, gallbladder dyplasia or gallbladder cancer using Illumina Infinium methylation arrays.
Project description:Although many protein-coding genes have been identified to be aberrantly expressed in gallbladder cancer, the mechanism that account for the development and progression of gallbladder cancer remains unclear. In recent years, long noncoding RNAs have been shown to play vital roles in mammalian cell biology. In this study, we found that a small number of lncRNAs that are aberrantly expressed. A ten chip study using total RNA recovered five separate gallbladder cancer tissues and five matched adjacent gallbladder normal tissues
Project description:Gallbladder cancer (GBC) comprises the most common biliary tract cancer (BTC). However, GBC is a rare disease often manifesting as aggressive malignancy due to its late diagnosis and resistance to chemotherapy. The identification of molecular drivers of GBC and identification of targeted therapies is still urgently needed. This study combined proteomic analysis of GBC patient samples, functional and molecular characterization of potential oncogenes, and identification of potential therapy strategy for GBC. We identified Carcinoembryonic Antigen-related Cell Adhesion Molecule 6 (CEACAM6) as one of the strongest and most significant upregulated proteins in GBC samples. Functional analysis and in vivo mouse models revealed that CEACAM6 supported the initial steps of cancer metastasis by decreasing cell adhesion while promoting migration and invasion of GBC cells. BirA-BioID followed by mass-spectrometry revealed Integrin Beta-1 (ITGB1) and Protein Kinase C Delta (PRKCD) as direct molecular and functional partners of CEACAM6 in supporting GBC cell migration through regulation of ERK and AKT downstream target genes MMP13, MMP14, and OCLN. Conversely, CEACAM6 knockdown abolished GBC aggressiveness, and treatment using AKT inhibitor Capivasertib and ERK inhibitor Ulixertinib counter-acted the CEACAM6-induced migration.These findings demonstrate that CEACAM6 is crucial for gallbladder oncogenesis through ERK and AKT signaling, providing insights into the design of therapeutic strategies for GBC.
Project description:Gallbladder carcinoma (GBC) is a rare cancer entity in Western Europe and the US with an incidence of less than 3/100.000 and a survival rate <10%. Radical surgery is the only potentially curative treatment option but most patients diagnosed with GBC are not resectable. Thus, there is a great need for the development of new treatment options, including targeted therapy for GBC. To dissect the epigenetic regulation during GBC development, we performed global miRNA profiling of 40 GBC and 8 normal gallbladder tissues. MiRNAs that are associated with survival were functionally analysed by cell proliferation and colony formation assays. In addition, we performed whole genome gene expression analysis of cells expressing miRNA mimics or control and performed biochemical assays to dissect miR-145 signalling. The GBC miRNA profiles exhibited large differences compared to normal gallbladder tissues with 49% of miRNAs being differentially expressed (FDR<0.001). In addition, 8 miRNAs were found to be down- and 16 to be up regulated in the GBCs with poor outcome (p<0.05). The most down regulated miRNA was miR-145-5p and the top up regulated miRNA was miR-575. Overexpression of miR-145 led to a significant reduction of cell proliferation and colony formation, whereas, opposite effects were observed for miR-575. Gene expression profiling of cells overexpressing miR-145 revealed activation of the STAT1 signalling pathway by inhibition of PTPRF in cholangiocellular but not hepatocellular carcinoma cells. Thereby, PTPRF directly bound to STAT1 and reduced STAT1 phosphorylation. This study identified pro- and anti-tumorigenic miRNAs in GBC and provides new mechanistic insight in the tumour suppressive function of miR-145 loss leading to active STAT1 signalling.