The increased expression of PLK1 (polo-like kinase 1) and its substrate MISP (mitotic spindle positioning) in intrahepatic cholangiocarcinoma tumor samples
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE244331 | GEO | 2026/09/10
REPOSITORIES: GEO
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Project description:Intrahepatic cholangiocarcinoma (iCCA) is an aggressive liver bile duct cancer with a poor prognosis. For advanced iCCA patients, Gemcitabine (GEM)-based chemotherapy is the standard treatment. Since there is only a 20-30% response rate for advanced CCA patients, it is a critical issue to counteract GEM resistance (GR). We selected two GR iCCA sublines (SSP-25-GR and KKU-213-GR) from the parental cells (SSP-25 and KKU-213) to determine the transcriptome profile.
2026-09-16 | GSE292343 | GEO
Project description:Cholangiocarcinoma (CCA) is a deadly tumour lacking effective therapies. Clinically-relevant experimental models and analysis of human samples represent the cornerstone of mechanistic cancer research. Thioacetamide (TAA)-induced intrahepatic CCA (iCCA) in rats encompasses key histological and molecular features of human iCCA. Molecular studies in bile may capture carcinogenic alterations and therapeutic vulnerabilities in CCA. We performed bile proteomic and metabolomic analyses in this model leading us to identify unrecognized mechanisms relevant to human iCCA.
2022-06-09 | PXD032802 | Pride
Project description:Background: Epigenetic alterations play an increasingly recognized role in carcinogenesis and in the development of resistance to anticancer therapies. Epigenetic enzymes (writers and erasers) and effectors (readers) are largely influenced by the availability of metabolites grenerated through one-carbon metabolism (OCM), the tricarboxylic acid (TCA) cycle, and acetyl-CoA synthesis (ACS). In this study we examined the expression of epigenetic and metabolic genes to investigate their interplay in cholangiocarcinoma (CCA). Method: We examined 257 epigenetic genes (EpiGs), 96 metabolic genes (MGs), and 189 rate-limiting enzymes (RLEs) in transcriptomic data from iCCA, eCCA, CCA organoids, and normal bile ducts, alongside prognostic signatures. CRISPR-Cas9 DepMap data evaluated the impact of EpiGs and MGs on cell viability. HuCCT-1 iCCA cells were exposed to hypoxia (1% O₂, 24 h) to assess EpiG responses. Transcriptomic deconvolution characterized EpiGs, MGs, and RLEs expression across four tumor microenvironment (TME) subtypes. Two mouse CCA models (Akt/TAZ, Akt/NICD) underwent RNA-seq, complemented by multi-omic profiling (transcriptomic, proteomic, metabolomic) in Akt/TAZ livers. Results: Several EpiGs were upregulated in iCCA and eCCA, including writers (DNMT1, EZH2, SUZ12), readers (CBX3, PHF20L1, SMARCA4), and erasers (HDAC1, HDAC3, KDM5C). MGs in OCM, TCA, and ACS pathways were dysregulated (up: GART, IDH2, TYMS; down: ALDH1L1, MAT1A, SHMT1). Integrated analyses identified 27 EpiGs and 8 MGs whose overexpression predicted poor survival. Subsets of EpiGs, MGs, and RLEs were linked to proliferative, high-recurrence iCCA subclasses. CRISPR screens highlighted 50 EpiGs and 23 MGs essential for CCA viability. Tumor microenvironment (TME) analyses revealed distinct immune-stromal subclasses with coherent epigenetic–metabolic signatures. In CCA cells, hypoxia induced epigenetic programs that mirrored those in CCA patients. Transcriptomic analyses in human and multi-omic analyses (transcriptomic, metabolomic, and proteomic studies) in mouse CCA livers highlighted rewiring of nucleotide, one-carbon, lipid, and mitochondrial pathways, with evidence of metabolic-epigenetic crosstalk. Conclusion: EpiGs and MGs are markedly altered in both human and experimental CCA, with several changes particularly enriched in aggressive molecular subclasses associated with poor prognosis. We observed substantial rewiring of epigenetic cofactor-related MG expression in CCAs. Functional assays validated new targets among EpiGs (e.g. CBX3, CHD4, DEK, SMARCA4, and TRIM28) and MGs (TYMS and IDH2) in CCA.
2026-06-29 | PXD072211 | Pride
Project description:Cholangiocarcinoma (CCA) is an aggressive liver bile duct cancer with a poor prognosis. For advanced CCA patients, Gemcitabine (GEM)-based chemotherapy is the standard treatment. Since there is only a 20-30% response rate for advanced CCA patients, it is a critical issue to counteract GEM resistance (GR). We selected two GR iCCA sublines (SSP-25-GR and SNU-1196-GR) from the parental cells (SSP-25 and SNU-1196) to determine the transcriptome profile.
2026-09-16 | GSE291223 | GEO
Project description:The increased expression of PLK1 (polo-like kinase 1) and its substrate MISP (mitotic spindle positioning) in intrahepatic cholangiocarcinoma tumor samples
| PRJNA1022414 | ENA
Project description:Intrahepatic cholangiocarcinoma (iCCA) is the second most common primary liver cancer. It is defined by cholangiocytic differentiation and has poor prognosis. Recently, epigenetic processes have been shown to play an important role in cholangiocarcinogenesis. We performed an integrative analysis on 52 iCCAs using both genetic and epigenetic data with a specific focus on DNA methylation components. We identified four major iCCA subgroups with widespread genomic and epigenomic differences and prognostic implications. Furthermore, our data suggest differences in the cell-of-origin of the iCCA subtypes.
2022-08-12 | GSE201241 | GEO
Project description:Intrahepatic Cholangiocarcinoma (iCCA) is a difficult type of cancer to diagnose, extremely aggressive and resistant to therapeutic options with an increased incidence and mortality over time. The overexpression of Notch pathway is implicated in iCCA to create an ecosystem that drives the tumor aggressiveness. Specifically, Notch1 is overexpressed in iCCA tissue of patients, playing an important role on tumor growth. Our purpose was to investigate the effectiveness of Crenigacestat in in vivo experiments, using Hucct1 injected in CD1 mice to generate an iCCA xenograft mouse model. In the present study, in order to explore modulated factors and genes by treatment we performed a transcriptomic analysis validated by Western Blotting and qRT-PCR on iCCA tumor masses of xenograft mice. Our results indicate that the treatment significantly inhibited Notch1 and HES1 genes and proteins triggering a strong immune response. Nevertheless, moderate fibrosis was shown in this model which may have hindered response to therapy to promote tumor progression. We used microarray technology to understand the molecular mechanisms affected by Crenigacestat in HUCCT1 xenograft model of intraepatic cholangiocarcinoma.
2022-04-27 | GSE150024 | GEO
Project description:Background and aims: Primary liver cancers (LCs), including HCC and intrahepatic cholangiocarcinoma (iCCA), are derived from a common developmental lineage, conferring a molecular spectrum between them. To elucidate the molecular spectrum, we performed an integrative analysis of transcriptome profiles associated with patients' radiopathologic features. Approach and results: We identified four LC subtypes (LC1-LC4) from RNA-sequencing profiles, revealing intermediate subtypes between HCC and iCCA. LC1 is a typical HCC characterized by active bile acid metabolism, telomerase reverse transcriptase promoter mutations, and high uptake of gadoxetic acid in MRI. LC2 is an iCCA-like HCC characterized by expression of the progenitor cell-like trait, tumor protein p53 mutations, and rim arterial-phase hyperenhancement in MRI. LC3 is an HCC-like iCCA, mainly small duct (SD) type, associated with HCC-related etiologic factors. LC4 is further subclassified into LC4-SD and LC4-large duct iCCAs according to the pathological features, which exhibited distinct genetic variations (e.g., KRAS , isocitrate dehydrogenase 1/2 mutation, and FGF receptor 2 fusion), stromal type, and prognostic outcomes. Conclusions: Our integrated view of the molecular spectrum of LCs can identify subtypes associated with transcriptomic, genomic, and radiopathologic features, providing mechanistic insights into heterogeneous LC progression.
2022-07-12 | GSE179443 | GEO
Project description:Intrahepatic cholangiocarcinoma (iCCA) is a fatal bile duct cancer with dismal prognosis and limited therapeutic options. By performing RNA- and exome sequencing analyses we have discovered a novel fusion event, FGFR2-PPHLN1 (16%), and damaging mutations in the ARAF oncogene (11%). Methods: mRNA and gDNA were exctracted from fresh frozen tumor tissues and corresponding normal tissue (n=8 pairs) from patients with iCCA who underwent surgical resection. RNA-seq was performed using Illumina HiSeq 2500 System with 100 nucleotide single-end reads. One sample and its paired non-tumoral tissue were eliminated from the subsequent analysis because of bad RNa quality. The same 8 paired tumors were also analyzed by whole-exome seq. Submitter confirms there are no patient privacy concerns with these data. This dataset is part of the TransQST collection.
2015-01-22 | E-GEOD-63420 | biostudies-arrayexpress
Project description:Background and Aims: Epithelial-mesenchymal transition (EMT) is involved in metastatic dissemination and associated with the progression of cholangiocarcinoma (CCA). Aquaporin-1 (AQP1) is a water channel expressed by cholangiocytes described to modulate cell proliferation and invasion in several cancers. However, the role of AQP1 in CCA remains unknown. Our aim was to study the function of AQP1 in CCA. Material and methods: AQP1 expression was evaluated in 39 human intrahepatic CCA (iCCA) by transcriptomic analysis. AQP1-KO in CCA cells, HucCCT1 was achieved by CRISPR/Cas9. Incucyte live-cell imaging system was used for functional studies. Next-generation sequencing (RNAseq) was used to further study the consequences of AQP1 KO. EMT and signaling pathways were evaluated by RT-qPCR, western blot, and immunostaining. In vivo experiments were performed using a xenograft CCA model. Results: AQP1 expression correlated positively with overall survival in patients with iCCA and negatively with EMT, stemness, and proliferative signatures. In vitro, RNA-seq analysis of CCA cells depleted for AQP1 showed a downregulation of epithelial markers (CDH1 and KRT19; p< 0.001) and an upregulation of mesenchymal markers (VIM and FN1; p < 0.001). In these cells, we observed a phenotypic change with induction of cell scattering, a loss of cell-cell junction protein E-cadherin, and a higher expression of vimentin and ZEB1, an EMT-inducing transcription factor. Functionally, loss of AQP1 is associated with increased cell migration and proliferation. Moreover, we found an activation of the IGF2/IGF1R/IR pathway in AQP1-depleted CCA cells. In vivo, AQP1-depleted CCA cells displayed a higher tumorigenic potential and tumor burden than control cells. Conclusion: Our data suggest that AQP1 acts as a tumor suppressor in CCA by acting both on cell proliferation and migration through an EMT process. Therefore, AQP1 might have an important role in the regulation of CCA progression.
2025-10-06 | GSE255001 | GEO