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pmid:28988016
Characterisation of the immune-related transcriptome in resected biliary tract cancers.
Michele Ghidini · Luciano Cascione · Pietro Carotenuto · Andrea Lampis · Francesco Trevisani · Maria Chiara Previdi · Jens C Hahne · Ian Said-Huntingford · Maya Raj · Alessandro Zerbi · Claudia Mescoli · Umberto Cillo · Massimo Rugge · Massimo Roncalli · Guido Torzilli · Lorenza Rimassa · Armando Santoro · Nicola Valeri · Matteo Fassan · Chiara Braconi
European journal of cancer (Oxford, England : 1990) · 2017 doi:10.1016/j.ejca.2017.09.005
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Complete file
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In these studies, nCounter PanCancer Immune Profiling Panel was used to assess the expression of 770 immune-related transcripts in the tumour tissues (TTs) and matched adjacent tissues (ATs) of resected BTCs. Cox regression analysis and Kaplan-Meier methods were used to correlate findings with relapse-free survival (RFS). The first analysis in the TT and AT of an exploratory set (n = 22) showed deregulation of 39 transcripts associated with T-cell activation. Risk of recurrence was associated with a greater number of genes deregulated in AT in comparison to TT. Analysis in the whole set (n = 53) showed a correlation between AT cytotoxic T-lymphocyte antigen-4 (CTLA4) expression and RFS, which maintained statistical significance at multivariate analysis. CTLA4 expression correlated with forkhead box P3 (FOXP3) expression, suggesting enrichment in T regulatory cells. CTLA4 is known to act by binding to the cluster of differentiation 80 (CD80). No association was seen between AT CD80 expression and RFS. However, CD80 expression differentiated prognosis in patients who received adjuvant chemotherapy. We showed that the immunomodulatory transcriptome is deregulated in resected BTCs. Our study includes a small number of patients and does not enable to draw definitive conclusions; however, it provides useful insights into potential transcripts that may deserve further investigation in larger cohorts of patients.\nTRANSCRIPT PROFILING: Nanostring data have been submitted to GEO repository: GSE90698 and GSE90699.", "claims": [{"id": "claim-method", "statement": "Cox regression analysis and Kaplan–Meier methods were used to correlate findings with relapse-free survival (RFS).", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:28988016", "locator": "sections[0] \"Abstract\" paragraph 1", "quote": "Cox regression analysis and Kaplan–Meier methods were used to correlate findings with relapse-free survival (RFS)."}], "state": "complete"}, {"id": "claim-data-access", "statement": "Nanostring data have been submitted to GEO repository: GSE90698 and GSE90699.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:28988016", "locator": "sections[0] \"Abstract\" paragraph 2", "quote": "Nanostring data have been submitted to GEO repository: GSE90698 and GSE90699."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "The headline result was that adjacent-tissue CTLA4 expression correlated with relapse-free survival in the 53-patient cohort, with median relapse-free survival of 16.27 months in high-expression cases versus 29.53 months in low-expression cases; Cox regression and Kaplan–Meier methods were used, and the NanoString source data were deposited in GEO under accessions GSE90698 and GSE90699.", "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:28988016"], "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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