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.
journal_name
Int J Mol Scijournal_title
International journal of molecular sciencesauthors
Gullo I,Carvalho J,Martins D,Lemos D,Monteiro AR,Ferreira M,Das K,Tan P,Oliveira C,Carneiro F,Oliveira Pdoi
10.3390/ijms19072079subject
Has Abstractpub_date
2018-07-17 00:00:00issue
7issn
1422-0067pii
ijms19072079journal_volume
19pub_type
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