Molecular profiling reveals potential targets in cholangiocarcinoma.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:37476584", "kind": "science-record", "revision": 4, "content_hash": "sha256:ecb3afa8425d34676cd57e8383d184d84341b7d4cd9daf90c1d09d6834564f01", "created_at": "2026-11-01T19:02:14Z", "updated_at": "2026-11-01T22:52:21Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Molecular profiling reveals potential targets in cholangiocarcinoma.", "doi": "10.3748/wjg.v29.i25.4053", "pmid": "37476584", "authors": ["Dan Liu", "Yang Shi", "Hongze Chen", "Muhammad Azhar Nisar", "Nicholas Jabara", "Noah Langwinski", "Sophia Mattson", "Katsuya Nagaoka", "Xuewei Bai", "Shaolei Lu", "Chiung-Kuei Huang"], "journal": "World journal of gastroenterology", "year": 2023, "abstract": "BACKGROUND: Cholangiocarcinoma (CCA) is a devastating malignancy and has a very poor prognosis if tumors spread outside the liver. Understanding the molecular mechanisms underlying the CCA progression will likely yield therapeutic approaches toward treating this deadly disease.\nAIM: To determine the molecular pathogenesis in CCA progression.\nMETHODS: In silico analysis, in vitro cell culture, CCA transgenic animals, histological, and molecular assays were adopted to determine the molecular pathogenesis.\nRESULTS: The transcriptomic data of human CCA samples were retrieved from The Cancer Genome Atlas (TGCA, CHOL), European Bioinformatics Institute (EBI, GAD00001001076), and Gene Expression Omnibus (GEO, GSE107943) databases. Using Gene set enrichment analysis, the cell cycle and Notch related pathways were demonstrated to be significantly activated in CCA in TCGA and GEO datasets. We, through differentially expressed genes, found several cell cycle and notch associated genes were significantly up-regulated in cancer tissues when compared with the non-cancerous control samples. The associated genes, via quantitative real-time PCR and western blotting assays, were further examined in normal human cholangiocytes, CCA cell lines, mouse normal bile ducts, and mouse CCA tumors established by specifically depleting P53 and expressing KrasG12D mutation in the liver. Consistently, we validated that the cell cycle and Notch pathways are up-regulated in CCA cell lines and mouse CCA tumors. Interestingly, targeting cell cycle and notch pathways using small molecules also exhibited significant beneficial effects in controlling tumor malignancy. More importantly, we demonstrated that several cell cycle and Notch associated genes are significantly associated with poor overall survival and disease-free survival using the Log-Rank test.\nCONCLUSION: In summary, our study comprehensively analyzed the gene expression pattern of CCA samples using publicly available datasets and identified the cell cycle and Notch pathways are potential therapeutic targets in this deadly disease.", "claims": [{"id": "claim-method", "statement": "The Kaplan-Meier analysis was performed to evaluate the OS and disease-free survival (DFS) of patients from GEO and EBI cohorts. The optimal cutoff point for two groups was estimated based on maximally selected rank statistics[16], and then significance of survival analysis was calculated using log-rank test between the two groups.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:37476584", "locator": "sections[7] \"Survival analysis\" paragraph 2", "quote": "The Kaplan-Meier analysis was performed to evaluate the OS and disease-free survival (DFS) of patients from GEO and EBI cohorts. The optimal cutoff point for two groups was estimated based on maximally selected rank statistics[16], and then significance of survival analysis was calculated using log-rank test between the two groups."}], "state": "complete"}, {"id": "claim-data-access", "statement": "No additional data are available.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:37476584", "locator": "sections[35] \"Data sharing statement\" paragraph 2", "quote": "No additional data are available."}], "state": "complete"}, {"id": "claim-target-result", "statement": "Several cell cycle and Notch associated genes were significantly associated with poor overall survival and disease-free survival using the Log-Rank test.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:37476584", "locator": "sections[0] \"Abstract\" paragraph 4", "quote": "More importantly, we demonstrated that several cell cycle and Notch associated genes are significantly associated with poor overall survival and disease-free survival using the Log-Rank test."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "Several cell cycle and Notch associated genes were significantly associated with poor overall survival and disease-free survival using the Log-Rank test.", "steps": [{"id": "read_published_estimate", "order": 1, "name": "Read the published estimate from the source", "kind": "other", "state": "complete", "blocked_on": null, "description": "The claim, method and evidence span published with the source article.", "duration_hours": null, "parameters": {}, "inputs": ["source:pmid:37476584"], "outputs": ["the published estimate and its evidence"], "instruments": [], "reagents": []}, {"id": "obtain_source_data", "order": 2, "name": "Obtain the source data from the named repository", "kind": "data-preparation", "state": "complete", "blocked_on": null, "description": "The GEO series accession resolves and its sample accessions are listed. 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The associated genes, via quantitative real-time PCR and western blotting assays, were further ex"], "order_basis": "paper_text_order:1156", "id": "assay:1"}, {"role": "data_generation", "definition_id": "western_blot", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.93, "evidence": ["ed genes, via quantitative real-time PCR and western blotting assays, were further examined in normal huma"], "order_basis": "paper_text_order:1174", "id": "assay:2"}, {"role": "data_generation", "definition_id": "animal_model", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.99, "evidence": ["normal human cholangiocytes, CCA cell lines, mouse normal bile ducts, and mouse CCA tumors esta", "CCA cell lines, mouse normal bile ducts, and mouse CCA tumors established by specifically deple", "hways are up-regulated in CCA cell lines and mouse CCA tumors. 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