Homo sapiens
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PROVIDER: PRJNA1242580 | ENA |
REPOSITORIES: ENA
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Project description:Introduction: Gallbladder cancer (GBC) is a highly aggressive malignancy with limited therapeutic options, particularly in underrepresented populations, including South Africa. Understanding the molecular landscape of GBC may provide novel insights into its pathogenesis and potential therapeutic targets. Molecular changes are known to be associated with GBC, however, there is a paucity of this information especially in African populations. Furthermore, within the tumour microenvironment, different immune cells contribute to GBC progression. We investigated gene expression patterns in GBC tumours and their association with different immune cells in a cohort of South African patients. Methods: RNA sequencing was conducted on 2 normal and 8 gallbladder cancer tissues from South African patients (Ethics: M160640) to identify differentially expressed genes. Bioinformatics tools were used for pathway analysis, while immune cell quantification was performed using the quanTIseq software and presented as median [IQR]. Verification studies were further carried out using real-time PCR on an independent cohort comprising 7 gallstone samples and 26 gallbladder tumour samples. Results: A total of 65 genes were found to be significantly differentially expressed between the gallbladder tumours and gallstone controls. We also identified 37 upregulated and 28 downregulated genes in this cohort. Among the most upregulated genes, MUC16 was confirmed to be significantly overexpressed in tumours. Normal tissues exhibited a significantly higher proportion of dysregulated genes associated with B cells (17.132 [14.866–18.483], p<0.0001) and M1 macrophages (18.943 [1.097–36.790], p<0.0001) compared to tumours. In contrast, tumours showed a greater association with dysregulated genes linked to regulatory T cells (Tregs) (14.373 [9.696–20.162]) relative to normal tissues. Pathway analysis further revealed the upregulation of defective GALNT12, defective GALNT3, defective C1GALT1C1 and termination of O-glycan biosynthesis, highlighting key mechanisms potentially involved in tumour progression. Conclusion: The study has shown the dysregulation of key genes in South African gallbladder cancer patients. Specifically, MUC16 was verified to be significantly elevated in tumour samples. Furthermore, the association of these dysregulated genes with key immune cells in this patient group may further highlight their roles in dysfunctional immune processes linked with tumourigenesis.
2025-12-04 | GSE308395 | GEO
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.
2024-10-30 | GSE243305 | GEO
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.
2024-10-30 | GSE243304 | GEO
Project description:Purpose Gallbladder cancer (GBC) is a highly malignant tumor with extremely poor prognosis. Previous studies have suggested that the carcinogenesis and progression of GBC is a multi-stage and multi-step process, but most of them focused on the genome changes. And a few studies just compared the transcriptome differences between tumor tissues and adjacent noncancerous tissues. The transcriptome changes, relating to every stage of GBC evolution, have rarely been studied. Methods We selected three cases of normal gallbladder, four cases of gallbladder with chronic inflammation induced by gallstones, five cases of early GBC, and five cases of advanced GBC, using next-generation RNA sequencing to reveal the changes in mRNAs and lncRNAs expression during the evolution of GBC. Results In-depth analysis of the sequencing data indicated that transcriptome changes from normal gallbladder to gallbladder with chronic inflammation were distinctly related to inflammation, lipid metabolism, and sex hormone metabolism; transcriptome changes from gallbladder with chronic inflammation to early GBC were distinctly related to immune activities and connection between cells; and the transcriptome changes from early GBC to advanced GBC were distinctly related to transmembrane transport of substances and migration of cells. Conclusion Expression profiles of mRNAs and lncRNAs change significantly during the evolution of GBC, in which lipid-based metabolic abnormalities play an important promotive role, inflammation and immune activities play a key role, and changes in membrane proteins are the most highlighted molecular changes.
2022-05-31 | GSE202479 | GEO
Project description:The present study aimed to understand the pathways involved in gallbladder cancer through genome-wide expression profiling (microarray) of human GBC
2025-02-06 | GSE255497 | GEO
Project description:Gallbladder cancer (GBC) poses a significant health burden with dismal prognosis due to frequent metastasis and recurrence. Although evodiamine has demonstrated potent inhibitory effects on proliferation and metastasis in various cancers, its role in GBC remains unexplored, and the underlying mechanisms are yet to be elucidated.
2026-01-04 | GSE312961 | GEO
Project description:APOBEC3s-related somatic mutations are the predominant burden in biliary tract cancers (BTCs). Here, we reveal the effects and mechanisms of APOBEC3A/3B functional polymorphisms on cholangiocarcinoma and gallbladder cancer (GBC). rs2267401-G at the APOBEC3B promoter decreases cholangiocarcinoma risk but increased GBC risk. rs2267401-G confers a decreased APOBEC3B promoter activity in cholangiocarcinoma cells but an increased activity in GBC cells. rs12157810-C at the APOBEC3A promoter decreases the risk of BTCs. rs12157810-C up-regulated the promoter activity in both cells. APOBEC3A overexpression attenuates cancer evolution via causing apoptosis, in contrast to APOBEC3B. Inflammatory factors promote cancer evolution via interacting with transcriptional repressors regulating the APOBEC3A/3B promoters. ATAC-seq was used to identify the difference between transcriptional networks of cholangiocarcinoma and GBC.
2022-01-07 | GSE166372 | GEO
Project description:Treatment options for advanced gallbladder cancer (GBC) are scarce and usually rely on cytotoxic chemotherapy, but unfortunately the effectiveness of any regimen is limited, and recurrence rates are high. Here, we established and characterized two gemcitabine-resistant GBC cell sublines (NOZ GemR and TGBC1 GemR) to investigate the molecular mechanisms associated with acquired resistance in vitro. The transcriptome profiling of parental and gemcitabine resistant cells revealed differential expression of multiple protein-coding genes and enrichment of biological processes such as epithelial-to-mesenchymal transition and drug metabolism. On the other hand, quantitative phosphotyrosine proteomic analysis of NOZ GemR identified aberrantly dysregulated signaling pathways in resistant cells as well as active kinases, such as Abl, PDGFRA, EphB2 and members of the Src-family that could be novel therapeutic targets against drug resistance in GBC. In line with this, NOZ GemR cells showed increased sensitivity toward the multikinase inhibitor dasatinib compared with parental cells. In conclusion, our study describes transcriptome changes and altered signaling pathways occurring in gemcitabine-resistant gallbladder cancer cells, which greatly expands our understanding of the underlying mechanisms of acquired drug-resistance in GBC. Moreover, this new gemcitabine resistant GBC models could be exploited either to study alternative mechanisms of resistance or to explore new therapies for chemotherapy-refractory GBC.
2023-05-03 | PXD036348 | Pride
Project description:RNA extracted at 240min. Samples are rRNA depleted. Expression measurement of Homo sapiens genes.
2019-07-31 | GSE114179 | GEO
Project description:Transcriptomic Landscape of Gallbladder Cancer for Molecular Classification and Tumor Microenvironment Characterization
| PRJDB10737 | ENA