Ontology highlight
ABSTRACT:
PROVIDER: PRJNA786280 | ENA |
REPOSITORIES: ENA
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Project description:Purpose: The uncommonness of gallbladder cancer in the developed world has contributed to the generally poor understanding of the disease. The development of new and effective treatment has been and continues to be a major public health imperative. Methods: We report mutational and copy number analysis of 44 predominantly early-staged gallbladder tumors and 5-gallbladder cancer cell lines by a combination of directed and whole exome sequencing at an average coverage of 100X and above. Using gallbladder cancer cell lines and xenograft mouse models we performed phospho-proteome array profiling, followed by an in-depth functional characterization. Results: We describe recurrent activating ERBB2 somatic mutation in 6 of 44 gallbladder primary tumors with an overall mutation frequency of 13%, along with KRAS activating mutations in 3 of 44 samples. Consistent with whole exome findings, a phospho-proteomic array profile of 49-tyrosine kinase revealed constitutive phosphorylation of ERBB2 and EGFR that were found to heterodimerize. We demonstrate that treatment with ERBB2-specific, EGFR-specific shRNA or with covalent EGFR family inhibitor BIBW-2992 inhibits transformation, survival, migration, invasion, and tumor forming characteristics of gallbladder cancer cells harboring wild type or KRAS (G13D) but not KRAS (G12V) mutation. Furthermore, we show in vivo reduction in tumor size is paralleled by a reduction in the amounts of phospho-ERK in KRAS (G13D) but not in KRAS (G12V) xenografts, validating the in vitro findings Conclusion: Findings from this study implicate ERBB2 as an important therapeutic target in early stage gallbladder cancer. We also present the first evidence that the presence of KRAS (G12V), but not KRAS (G13D) mutation, may preclude gallbladder cancer patients to respond to anti-EGFR treatment, similar to the clinical algorithm commonly practiced to opt for anti-EGFR treatment in colorectal cancer.
2018-12-29 | E-MTAB-6619 | biostudies-arrayexpress
Project description:miRNA profiling in gallbladder carcinoma
| PRJNA411846 | ENA
Project description:Treatment with immune checkpoint inhibitors in colorectal cancer (CRC) has largely benefited patients with microsatellite instability–high (MSI-H) and not the larger proportion of patient with microsatellite-stable (MSS) tumors. This clinical dichotomy has fueled the view that high mutational burden is the dominant driver of tumor immunogenicity and that MSS CRC fails to respond because it is “antigen poor”. To directly test this premise and define the origins of presented tumor antigens, we integrated HLA class I immunopeptidomics and matched RNA-seq from 26 primary CRC tumors spanning MSI-H and MSS subtypes. Using patient-specific canonical and cancer-specific proteogenomic databases, we identified 115,292 unique MHC-associated peptides (MAPs) across 61 HLA alleles, with a mean of 9,292 MAPs per tumor and no significant difference in MAP counts between MSI-H and MSS tumors. In toto, we identified 266 tumor antigens, all coded by unmutated genomic sequences, comprising 70 aberrantly expressed tumor-specific antigens (aeTSAs) and 196 tumor-associated antigens (TAAs). In our cohort, MSS tumors presented more TAAs and a comparable number of aeTSAs per tumor relative to MSI-H tumors. In TCGA-COAD stratified analyses (483 tumors), MSS tumors yielded more presentable aeTSAs and TAAs per patient than MSI-H tumors. Across both subtypes, aeTSAs arose predominantly from intronic translation, UTR usage, retroelement activation, and germline-like transcription, including recurrent aeTSAs from PIWIL1, L1TD1, and endogenous retroviral loci. Together, these data demonstrate that MSS CRC is not antigen poor and highlight non-canonical translation as a major, previously underappreciated contributor to the CRC immunopeptidome.
2026-05-26 | GSE312236 | GEO
Project description:Proteins interacting with NSUN2 in gallbladder carcinoma (NOZ cell line)
2019-03-20 | PXD013152 |
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.
2016-01-08 | GSE76633 | GEO
Project description:Gemcitabine resistance in gallbladder cancer poses a significant challenge to patient prognosis. This study identified RUVBL2 as a critical factor contributing to gemcitabine resistance in gallbladder cancer. Further analysis, combining ChIP-seq and gene enrichment studies, revealed that RUVBL2 regulates the mitophagy pathway. This regulation helps maintain intracellular redox homeostasis in gallbladder cancer cells following gemcitabine treatment.
2026-01-30 | GSE317548 | GEO
Project description:The endocannabinoid system (ECS) is dysregulated in various liver diseases. Biliary tract cancers (BTCs) encompass gallbladder carcinoma, intrahepatic, perihilar and distal cholangiocarcinoma. Previously we have shown that the two major endocannabinoids (ECs), anandamide (AEA) and 2-arachidonoyl glycerol (2-AG) exerted opposing effects on BTCs cell lines in which 2-AG promoted tumor proliferation. The underlying mechanism and regulation of 2-AG on miRNAs expression in BTCs remain inconclusive.
2022-05-01 | GSE188863 | GEO
Project description:Sox17 expression is important for development of gallbladder and bile duct systems in embryo, and it is reported that gallbladder hypoplasia in Sox17 hetero genic embryo. Additionally it was reported that hepatitis was occurred in Sox17 hetero genic newborn by gallbladder hypoplasia. So, we examined Sox17 gene cascade and the role for the formation of gallbladder and bile duct systems by microarray analysis on Sox17 hetero genic gallbladder in day 15 of pregnancy when Sox17 express and gallbladder epithelium alternated morphology. We detected that expression of Sonic hedgehog (shh) signal genes decreased in sox17+/- gallbladder and cysticduct as compared with the wildtype gallbladders.These arry analysis in gallbladder and cysticduct reveal expression of shh in developmental gallbladder is downstream in sox17+/- and gene expression in sox17+/- gallbladder was similar in cysticduct .
2017-05-30 | GSE74576 | GEO
Project description:This study aimed to investigate the molecular mechanism underlying the effects of Cyp4f3b gene interference on the biological behaviors of human gallbladder carcinoma cells gbc-sd. Three replicate cell samples from each group (sh-NC control group and sh-Cyp4f3b interference group) were subjected to total RNA extraction and quality control, sequencing library construction and evaluation, RNA-seq sequencing and filtering, reference sequence alignment, gene expression level analysis, and differential expression analysis. Differentially expressed genes and significantly enriched signaling pathways were systematically identified to provide molecular evidence for clarifying the role of Cyp4f3b in gallbladder carcinogenesis and progression.
2026-03-25 | GSE325472 | GEO