The Transcriptomic Landscape of Gastric Cancer: Insights into Epstein-Barr Virus Infected and Microsatellite Unstable Tumors
AbstractBackground: 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. View Full-Text
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Gullo, I.; Carvalho, J.; Martins, D.; Lemos, D.; Monteiro, A.R.; Ferreira, M.; Das, K.; Tan, P.; Oliveira, C.; Carneiro, F.; Oliveira, P. The Transcriptomic Landscape of Gastric Cancer: Insights into Epstein-Barr Virus Infected and Microsatellite Unstable Tumors. Int. J. Mol. Sci. 2018, 19, 2079.
Gullo I, Carvalho J, Martins D, Lemos D, Monteiro AR, Ferreira M, Das K, Tan P, Oliveira C, Carneiro F, Oliveira P. The Transcriptomic Landscape of Gastric Cancer: Insights into Epstein-Barr Virus Infected and Microsatellite Unstable Tumors. International Journal of Molecular Sciences. 2018; 19(7):2079.Chicago/Turabian Style
Gullo, Irene; Carvalho, Joana; Martins, Diana; Lemos, Diana; Monteiro, Ana R.; Ferreira, Marta; Das, Kakoli; Tan, Patrick; Oliveira, Carla; Carneiro, Fátima; Oliveira, Patrícia. 2018. "The Transcriptomic Landscape of Gastric Cancer: Insights into Epstein-Barr Virus Infected and Microsatellite Unstable Tumors." Int. J. Mol. Sci. 19, no. 7: 2079.
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