{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,7]],"date-time":"2025-11-07T09:24:10Z","timestamp":1762507450574,"version":"build-2065373602"},"reference-count":44,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2018,7,17]],"date-time":"2018-07-17T00:00:00Z","timestamp":1531785600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001871","name":"Funda\u00e7\u00e3o para a Ci\u00eancia e a Tecnologia","doi-asserted-by":"publisher","award":["NORTE-01-0145-FEDER-000003","NORTE-01-0145-FEDER-000029","SFRH\/BPD\/86543\/2012","SFRH\/BPD\/89764\/2012"],"award-info":[{"award-number":["NORTE-01-0145-FEDER-000003","NORTE-01-0145-FEDER-000029","SFRH\/BPD\/86543\/2012","SFRH\/BPD\/89764\/2012"]}],"id":[{"id":"10.13039\/501100001871","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100008530","name":"European Regional Development Fund","doi-asserted-by":"publisher","award":["POCI-01-0145-FEDER-022184"],"award-info":[{"award-number":["POCI-01-0145-FEDER-022184"]}],"id":[{"id":"10.13039\/501100008530","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>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\u2212, 15 tested MSS\/EBV+ and four tested MSS\/EBV\u2212. 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\u2212 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\u2212 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.<\/jats:p>","DOI":"10.3390\/ijms19072079","type":"journal-article","created":{"date-parts":[[2018,7,18]],"date-time":"2018-07-18T08:45:42Z","timestamp":1531903542000},"page":"2079","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":32,"title":["The Transcriptomic Landscape of Gastric Cancer: Insights into Epstein-Barr Virus Infected and Microsatellite Unstable Tumors"],"prefix":"10.3390","volume":"19","author":[{"given":"Irene","family":"Gullo","sequence":"first","affiliation":[{"name":"Department of Pathology, Centro Hospitalar de S\u00e3o Jo\u00e3o, Porto 4200-319, Portugal"},{"name":"Department of Pathology, Faculty of Medicine of the University of Porto (FMUP), Porto 4200-319, Portugal"},{"name":"Institute of Molecular Pathology and Immunology, University of Porto (Ipatimup), Porto 4200-135, Portugal"},{"name":"Instituto de Investiga\u00e7\u00e3o e Inova\u00e7\u00e3o em Sa\u00fade (i3S), University of Porto, Porto 4200-135, Portugal"}]},{"given":"Joana","family":"Carvalho","sequence":"additional","affiliation":[{"name":"Institute of Molecular Pathology and Immunology, University of Porto (Ipatimup), Porto 4200-135, Portugal"},{"name":"Instituto de Investiga\u00e7\u00e3o e Inova\u00e7\u00e3o em Sa\u00fade (i3S), University of Porto, Porto 4200-135, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1457-8992","authenticated-orcid":false,"given":"Diana","family":"Martins","sequence":"additional","affiliation":[{"name":"Institute of Molecular Pathology and Immunology, University of Porto (Ipatimup), Porto 4200-135, Portugal"},{"name":"Instituto de Investiga\u00e7\u00e3o e Inova\u00e7\u00e3o em Sa\u00fade (i3S), University of Porto, Porto 4200-135, Portugal"}]},{"given":"Diana","family":"Lemos","sequence":"additional","affiliation":[{"name":"Institute of Molecular Pathology and Immunology, University of Porto (Ipatimup), Porto 4200-135, Portugal"},{"name":"Instituto de Investiga\u00e7\u00e3o e Inova\u00e7\u00e3o em Sa\u00fade (i3S), University of Porto, Porto 4200-135, Portugal"}]},{"given":"Ana Rita","family":"Monteiro","sequence":"additional","affiliation":[{"name":"Institute of Molecular Pathology and Immunology, University of Porto (Ipatimup), Porto 4200-135, Portugal"},{"name":"Instituto de Investiga\u00e7\u00e3o e Inova\u00e7\u00e3o em Sa\u00fade (i3S), University of Porto, Porto 4200-135, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3680-8613","authenticated-orcid":false,"given":"Marta","family":"Ferreira","sequence":"additional","affiliation":[{"name":"Institute of Molecular Pathology and Immunology, University of Porto (Ipatimup), Porto 4200-135, Portugal"},{"name":"Instituto de Investiga\u00e7\u00e3o e Inova\u00e7\u00e3o em Sa\u00fade (i3S), University of Porto, Porto 4200-135, Portugal"}]},{"given":"Kakoli","family":"Das","sequence":"additional","affiliation":[{"name":"Cancer and Stem Cell Biology Program, Duke-NUS Medical School, Singapore 169857, Singapore"}]},{"given":"Patrick","family":"Tan","sequence":"additional","affiliation":[{"name":"Cancer and Stem Cell Biology Program, Duke-NUS Medical School, Singapore 169857, Singapore"},{"name":"Genome Institute of Singapore, Biopolis, Singapore 138672, Singapore"},{"name":"Cancer Science Institute of Singapore, National University of Singapore, Singapore 117599, Singapore"}]},{"given":"Carla","family":"Oliveira","sequence":"additional","affiliation":[{"name":"Institute of Molecular Pathology and Immunology, University of Porto (Ipatimup), Porto 4200-135, Portugal"},{"name":"Instituto de Investiga\u00e7\u00e3o e Inova\u00e7\u00e3o em Sa\u00fade (i3S), University of Porto, Porto 4200-135, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1964-1006","authenticated-orcid":false,"given":"F\u00e1tima","family":"Carneiro","sequence":"additional","affiliation":[{"name":"Department of Pathology, Centro Hospitalar de S\u00e3o Jo\u00e3o, Porto 4200-319, Portugal"},{"name":"Department of Pathology, Faculty of Medicine of the University of Porto (FMUP), Porto 4200-319, Portugal"},{"name":"Institute of Molecular Pathology and Immunology, University of Porto (Ipatimup), Porto 4200-135, Portugal"},{"name":"Instituto de Investiga\u00e7\u00e3o e Inova\u00e7\u00e3o em Sa\u00fade (i3S), University of Porto, Porto 4200-135, Portugal"}]},{"given":"Patr\u00edcia","family":"Oliveira","sequence":"additional","affiliation":[{"name":"Institute of Molecular Pathology and Immunology, University of Porto (Ipatimup), Porto 4200-135, Portugal"},{"name":"Instituto de Investiga\u00e7\u00e3o e Inova\u00e7\u00e3o em Sa\u00fade (i3S), University of Porto, Porto 4200-135, Portugal"}]}],"member":"1968","published-online":{"date-parts":[[2018,7,17]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"50","DOI":"10.1159\/000473881","article-title":"Heterogeneity in Gastric Cancer: From Pure Morphology to Molecular Classifications","volume":"85","author":"Gullo","year":"2018","journal-title":"Pathobiology"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"419","DOI":"10.1007\/978-3-319-41388-4_21","article-title":"Genomics Study of Gastric Cancer and Its Molecular Subtypes","volume":"908","author":"Yuen","year":"2016","journal-title":"Adv. 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