Characterisation of the immune-related transcriptome in resected biliary tract cancers.
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Date
2017-11-01Author
Ghidini, M
Cascione, L
Carotenuto, P
Lampis, A
Trevisani, F
Previdi, MC
Hahne, JC
Said-Huntingford, I
Raj, M
Zerbi, A
Mescoli, C
Cillo, U
Rugge, M
Roncalli, M
Torzilli, G
Rimassa, L
Santoro, A
Valeri, N
Fassan, M
Braconi, C
Type
Journal Article
Metadata
Show full item recordAbstract
UNLABELLED: Although biliary tract cancers (BTCs) are known to have an inflammatory component, a detailed characterisation of immune-related transcripts has never been performed. 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. TRANSCRIPT PROFILING: Nanostring data have been submitted to GEO repository: GSE90698 and GSE90699.
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Subject
Lymphocytes, Tumor-Infiltrating
Humans
Biliary Tract Neoplasms
Disease-Free Survival
Treatment Outcome
Biliary Tract Surgical Procedures
Multivariate Analysis
Proportional Hazards Models
Retrospective Studies
Gene Expression Profiling
Tumor Escape
Gene Expression Regulation, Neoplastic
Time Factors
Adult
Aged
Middle Aged
Italy
Female
Male
T-Lymphocytes, Regulatory
Forkhead Transcription Factors
Kaplan-Meier Estimate
Tumor Microenvironment
CTLA-4 Antigen
Transcriptome
Biomarkers, Tumor
B7-1 Antigen
Research team
Signal Transduction & Molecular Pharmacology
Evolutionary Genomics & Modelling
Gastrointestinal Cancer Biology and Genomics
Language
eng
Date accepted
2017-09-04
License start date
2017-11
Citation
European journal of cancer (Oxford, England : 1990), 2017, 86 pp. 158 - 165
Publisher
ELSEVIER SCI LTD