Please use this identifier to cite or link to this item: https://doi.org/10.3390/ijms19072079
Title: The transcriptomic landscape of gastric cancer: Insights into epstein-barr virus infected and microsatellite unstable tumors
Authors: Gullo, I
Carvalho, J
Martins, D
Lemos, D
Monteiro, A.R
Ferreira, M
Das, K 
Tan, P 
Oliveira, C
Carneiro, F
Oliveira, P
Keywords: cytotoxic T lymphocyte antigen 4
messenger RNA
programmed death 1 ligand 1
programmed death 1 receptor
protein
protein Dies1
protein VISTA
unclassified drug
CD274 protein, human
programmed death 1 ligand 1
transcriptome
Article
bioinformatics
cancer immunotherapy
clinical article
correlation analysis
Epstein Barr virus
Epstein Barr virus infection
female
gene expression
human
human tissue
immune response
immunocompetent cell
immunohistochemistry
male
microsatellite instability
mitosis rate
molecular genetics
phenotype
protein expression
software
stomach cancer
stomach tumor
stroma cell
transcriptomics
cluster analysis
Epstein Barr virus
Epstein Barr virus infection
gene expression profiling
gene expression regulation
gene ontology
genetics
metabolism
physiology
procedures
retrospective study
virology
B7-H1 Antigen
Cluster Analysis
Epstein-Barr Virus Infections
Gene Expression Profiling
Gene Expression Regulation, Neoplastic
Gene Ontology
Herpesvirus 4, Human
Humans
Microsatellite Instability
Retrospective Studies
Stomach Neoplasms
Transcriptome
Issue Date: 2018
Publisher: MDPI
Citation: Gullo, I, Carvalho, J, Martins, D, Lemos, D, Monteiro, A.R, Ferreira, M, Das, K, Tan, P, Oliveira, C, Carneiro, F, Oliveira, P (2018). The transcriptomic landscape of gastric cancer: Insights into epstein-barr virus infected and microsatellite unstable tumors. International Journal of Molecular Sciences 19 (7) : 2079. ScholarBank@NUS Repository. https://doi.org/10.3390/ijms19072079
Rights: Attribution 4.0 International
Abstract: Background: Epstein-Barr Virus (EBV) positive and microsatellite unstable (MSI-high) gastric cancer (GC) are molecular subgroups with distinctive molecular profiles. We explored the transcriptomic differences between EBV+ and MSI-high GCs, and the expression of current GC immunotherapy targets such as PD-1, PD-L1, CTLA4 and Dies1/VISTA. Methods: Using Nanostring Technology and comparative bioinformatics, we analyzed the expression of 499 genes in 46 GCs, classified either as EBV positive (EBER in situ hybridization) or MSI-high (PCR/fragment analysis). PD-L1 protein expression was assessed by immunohistochemistry. Results: From the 46 GCs, 27 tested MSI-high/EBV?, 15 tested MSS/EBV+ and four tested MSS/EBV?. The Nanostring CodeSet could segregate GCs according to MSI and, to a lesser extent, EBV status. Functional annotation of differentially expressed genes associated MSI-high/EBV? GCs with mitotic activity and MSS/EBV+ GCs with immune response. PD-L1 protein expression, evaluated in stromal immune cells, was lower in MSI-high/EBV? GCs. High mRNA expression of PD-1, CTLA4 and Dies1/VISTA and distinctive PD-1/PD-L1 co-expression patterns (PD-1high/PD-L1low, PD-1high/PDL1high) were associated with MSS/EBV+ molecular subtype and gastric cancer with lymphoid stroma (GCLS) morphological features. Conclusions: EBV+ and MSI-high GCs present distinct transcriptomic profiles. GCLS/EBV+ cases frequently present co-expression of multiple immunotherapy targets, a finding with putative therapeutic implications. © 2018 by the authors. Licensee MDPI, Basel, Switzerland.
Source Title: International Journal of Molecular Sciences
URI: https://scholarbank.nus.edu.sg/handle/10635/183837
ISSN: 1661-6596
DOI: 10.3390/ijms19072079
Rights: Attribution 4.0 International
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