PD-L1 overexpression in EBV-positive gastric cancer is caused by unique genomic or epigenomic mechanisms
Abstract Epstein-Barr virus-positive gastric cancer [EBV (+) GC] is a distinct GC subtype with unique genetic and epigenetic aberrations. Here, we examined resected GC samples and publicly available microarray data and The Cancer Genome Atlas (TCGA) database to identify the mechanism underlying over...
Guardado en:
| Autores principales: | , , , , , , , , , , , , , , , , , , |
|---|---|
| Formato: | article |
| Lenguaje: | EN |
| Publicado: |
Nature Portfolio
2021
|
| Materias: | |
| Acceso en línea: | https://doaj.org/article/a90715074f9246faba8858abfb087e63 |
| Etiquetas: |
Agregar Etiqueta
Sin Etiquetas, Sea el primero en etiquetar este registro!
|
| id |
oai:doaj.org-article:a90715074f9246faba8858abfb087e63 |
|---|---|
| record_format |
dspace |
| spelling |
oai:doaj.org-article:a90715074f9246faba8858abfb087e632021-12-02T13:57:05ZPD-L1 overexpression in EBV-positive gastric cancer is caused by unique genomic or epigenomic mechanisms10.1038/s41598-021-81667-w2045-2322https://doaj.org/article/a90715074f9246faba8858abfb087e632021-01-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-81667-whttps://doaj.org/toc/2045-2322Abstract Epstein-Barr virus-positive gastric cancer [EBV (+) GC] is a distinct GC subtype with unique genetic and epigenetic aberrations. Here, we examined resected GC samples and publicly available microarray data and The Cancer Genome Atlas (TCGA) database to identify the mechanism underlying overexpression of PD-L1 in EBV (+) GC. We found that high levels of PD-L1 overexpression in EBV (+) GC were caused by focal amplification of CD274. By contrast, relatively high expression of PD-L1 in tumor tissue and infiltrating immune cells correlated with CD8 lymphocyte infiltration and IFN-γ expression via IRF3 activation. Since we reported previously that PD-L1 expression is associated both with the presence of CD8 T cells in the tumor microenvironment and with IFN-γ expression in GC, we examined a database to see whether IFN-γ-associated overexpression of PD-L1 plays a significant role in EBV (+) GC. Immunohistochemical staining showed that expression of the IRF3 signature in clinical GC samples was higher in EBV (+) than in EBV (−) cases. The data presented herein reveal a unique dual mechanism underlying PD-L1 overexpression in EBV (+) GC: high focal amplification of CD274 or IFN-γ-mediated signaling via activation of IRF3.Hiroshi NakanoMotonobu SaitoShotaro NakajimaKatsuharu SaitoYuko NakayamaKoji KaseLeo YamadaYasuyuki KankeHiroyuki HanayamaHisashi OnozawaHirokazu OkayamaShotaro FujitaWataru SakamotoZenichiro SazeTomoyuki MommaKosaku MimuraShinji OhkiAkiteru GotoKoji KonoNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-12 (2021) |
| institution |
DOAJ |
| collection |
DOAJ |
| language |
EN |
| topic |
Medicine R Science Q |
| spellingShingle |
Medicine R Science Q Hiroshi Nakano Motonobu Saito Shotaro Nakajima Katsuharu Saito Yuko Nakayama Koji Kase Leo Yamada Yasuyuki Kanke Hiroyuki Hanayama Hisashi Onozawa Hirokazu Okayama Shotaro Fujita Wataru Sakamoto Zenichiro Saze Tomoyuki Momma Kosaku Mimura Shinji Ohki Akiteru Goto Koji Kono PD-L1 overexpression in EBV-positive gastric cancer is caused by unique genomic or epigenomic mechanisms |
| description |
Abstract Epstein-Barr virus-positive gastric cancer [EBV (+) GC] is a distinct GC subtype with unique genetic and epigenetic aberrations. Here, we examined resected GC samples and publicly available microarray data and The Cancer Genome Atlas (TCGA) database to identify the mechanism underlying overexpression of PD-L1 in EBV (+) GC. We found that high levels of PD-L1 overexpression in EBV (+) GC were caused by focal amplification of CD274. By contrast, relatively high expression of PD-L1 in tumor tissue and infiltrating immune cells correlated with CD8 lymphocyte infiltration and IFN-γ expression via IRF3 activation. Since we reported previously that PD-L1 expression is associated both with the presence of CD8 T cells in the tumor microenvironment and with IFN-γ expression in GC, we examined a database to see whether IFN-γ-associated overexpression of PD-L1 plays a significant role in EBV (+) GC. Immunohistochemical staining showed that expression of the IRF3 signature in clinical GC samples was higher in EBV (+) than in EBV (−) cases. The data presented herein reveal a unique dual mechanism underlying PD-L1 overexpression in EBV (+) GC: high focal amplification of CD274 or IFN-γ-mediated signaling via activation of IRF3. |
| format |
article |
| author |
Hiroshi Nakano Motonobu Saito Shotaro Nakajima Katsuharu Saito Yuko Nakayama Koji Kase Leo Yamada Yasuyuki Kanke Hiroyuki Hanayama Hisashi Onozawa Hirokazu Okayama Shotaro Fujita Wataru Sakamoto Zenichiro Saze Tomoyuki Momma Kosaku Mimura Shinji Ohki Akiteru Goto Koji Kono |
| author_facet |
Hiroshi Nakano Motonobu Saito Shotaro Nakajima Katsuharu Saito Yuko Nakayama Koji Kase Leo Yamada Yasuyuki Kanke Hiroyuki Hanayama Hisashi Onozawa Hirokazu Okayama Shotaro Fujita Wataru Sakamoto Zenichiro Saze Tomoyuki Momma Kosaku Mimura Shinji Ohki Akiteru Goto Koji Kono |
| author_sort |
Hiroshi Nakano |
| title |
PD-L1 overexpression in EBV-positive gastric cancer is caused by unique genomic or epigenomic mechanisms |
| title_short |
PD-L1 overexpression in EBV-positive gastric cancer is caused by unique genomic or epigenomic mechanisms |
| title_full |
PD-L1 overexpression in EBV-positive gastric cancer is caused by unique genomic or epigenomic mechanisms |
| title_fullStr |
PD-L1 overexpression in EBV-positive gastric cancer is caused by unique genomic or epigenomic mechanisms |
| title_full_unstemmed |
PD-L1 overexpression in EBV-positive gastric cancer is caused by unique genomic or epigenomic mechanisms |
| title_sort |
pd-l1 overexpression in ebv-positive gastric cancer is caused by unique genomic or epigenomic mechanisms |
| publisher |
Nature Portfolio |
| publishDate |
2021 |
| url |
https://doaj.org/article/a90715074f9246faba8858abfb087e63 |
| work_keys_str_mv |
AT hiroshinakano pdl1overexpressioninebvpositivegastriccanceriscausedbyuniquegenomicorepigenomicmechanisms AT motonobusaito pdl1overexpressioninebvpositivegastriccanceriscausedbyuniquegenomicorepigenomicmechanisms AT shotaronakajima pdl1overexpressioninebvpositivegastriccanceriscausedbyuniquegenomicorepigenomicmechanisms AT katsuharusaito pdl1overexpressioninebvpositivegastriccanceriscausedbyuniquegenomicorepigenomicmechanisms AT yukonakayama pdl1overexpressioninebvpositivegastriccanceriscausedbyuniquegenomicorepigenomicmechanisms AT kojikase pdl1overexpressioninebvpositivegastriccanceriscausedbyuniquegenomicorepigenomicmechanisms AT leoyamada pdl1overexpressioninebvpositivegastriccanceriscausedbyuniquegenomicorepigenomicmechanisms AT yasuyukikanke pdl1overexpressioninebvpositivegastriccanceriscausedbyuniquegenomicorepigenomicmechanisms AT hiroyukihanayama pdl1overexpressioninebvpositivegastriccanceriscausedbyuniquegenomicorepigenomicmechanisms AT hisashionozawa pdl1overexpressioninebvpositivegastriccanceriscausedbyuniquegenomicorepigenomicmechanisms AT hirokazuokayama pdl1overexpressioninebvpositivegastriccanceriscausedbyuniquegenomicorepigenomicmechanisms AT shotarofujita pdl1overexpressioninebvpositivegastriccanceriscausedbyuniquegenomicorepigenomicmechanisms AT watarusakamoto pdl1overexpressioninebvpositivegastriccanceriscausedbyuniquegenomicorepigenomicmechanisms AT zenichirosaze pdl1overexpressioninebvpositivegastriccanceriscausedbyuniquegenomicorepigenomicmechanisms AT tomoyukimomma pdl1overexpressioninebvpositivegastriccanceriscausedbyuniquegenomicorepigenomicmechanisms AT kosakumimura pdl1overexpressioninebvpositivegastriccanceriscausedbyuniquegenomicorepigenomicmechanisms AT shinjiohki pdl1overexpressioninebvpositivegastriccanceriscausedbyuniquegenomicorepigenomicmechanisms AT akiterugoto pdl1overexpressioninebvpositivegastriccanceriscausedbyuniquegenomicorepigenomicmechanisms AT kojikono pdl1overexpressioninebvpositivegastriccanceriscausedbyuniquegenomicorepigenomicmechanisms |
| _version_ |
1718392339434569728 |