Please use this identifier to cite or link to this item: https://hdl.handle.net/10216/127036
Author(s): Gullo I
Carvalho J
Martins D
Lemos D
Monteiro AR
Ferreira M
Das K
Tan P
Oliveira C
Carneiro F
Oliveira P
Title: The transcriptomic landscape of gastric cancer: Insights into epstein-barr virus infected and microsatellite unstable tumors
Publisher: MDPI
Issue Date: 2018
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.
URI: https://hdl.handle.net/10216/127036
Source: International Journal of Molecular Sciences, vol.19(7):2079
Related Information: info:eu-repo/grantAgreement/FCT/SFRH/SFRH%2FBPD%2F89764%2F2012/PT
info:eu-repo/grantAgreement/FCT/SFRH/SFRH%2FBPD%2F86543%2F2012/PT
Document Type: Artigo em Revista Científica Internacional
Rights: openAccess
License: https://creativecommons.org/licenses/by/4.0/
Appears in Collections:I3S - Artigo em Revista Científica Internacional

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