Epstein-barr virus infected gastric adenocarcinoma expresses latent and lytic viral transcripts and has a distinct human gene expression profile
Background EBV DNA is found within the malignant cells of 10% of gastric cancers. Modern molecular technology facilitates identification of virus-related biochemical effects that could assist in early diagnosis and disease management. Methods In this study, RNA expression profiling was performed on...
Ausführliche Beschreibung
Autor*in: |
Tang, Weihua [verfasserIn] |
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E-Artikel |
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Englisch |
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2012 |
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© Tang et al.; licensee BioMed Central Ltd. 2012. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( |
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Übergeordnetes Werk: |
Enthalten in: Infectious agents and cancer - London : Biomed Central, 2006, 7(2012), 1 vom: 28. Aug. |
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Übergeordnetes Werk: |
volume:7 ; year:2012 ; number:1 ; day:28 ; month:08 |
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DOI / URN: |
10.1186/1750-9378-7-21 |
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SPR029520649 |
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245 | 1 | 0 | |a Epstein-barr virus infected gastric adenocarcinoma expresses latent and lytic viral transcripts and has a distinct human gene expression profile |
264 | 1 | |c 2012 | |
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520 | |a Background EBV DNA is found within the malignant cells of 10% of gastric cancers. Modern molecular technology facilitates identification of virus-related biochemical effects that could assist in early diagnosis and disease management. Methods In this study, RNA expression profiling was performed on 326 macrodissected paraffin-embedded tissues including 204 cancers and, when available, adjacent non-malignant mucosa. Nanostring nCounter probes targeted 96 RNAs (20 viral, 73 human, and 3 spiked RNAs). Results In 182 tissues with adequate housekeeper RNAs, distinct profiles were found in infected versus uninfected cancers, and in malignant versus adjacent benign mucosa. EBV-infected gastric cancers expressed nearly all of the 18 latent and lytic EBV RNAs in the test panel. Levels of EBER1 and EBER2 RNA were highest and were proportional to the quantity of EBV genomes as measured by Q-PCR. Among protein coding EBV RNAs, EBNA1 from the Q promoter and BRLF1 were highly expressed while EBNA2 levels were low positive in only 6/14 infected cancers. Concomitant upregulation of cellular factors implies that virus is not an innocent bystander but rather is linked to NFKB signaling (FCER2, TRAF1) and immune response (TNFSF9, CXCL11, IFITM1, FCRL3, MS4A1 and PLUNC), with PPARG expression implicating altered cellular metabolism. Compared to adjacent non-malignant mucosa, gastric cancers consistently expressed INHBA, SPP1, THY1, SERPINH1, CXCL1, FSCN1, PTGS2 (COX2), BBC3, ICAM1, TNFSF9, SULF1, SLC2A1, TYMS, three collagens, the cell proliferation markers MYC and PCNA, and EBV BLLF1 while they lacked CDH1 (E-cadherin), CLDN18, PTEN, SDC1 (CD138), GAST (gastrin) and its downstream effector CHGA (chromogranin). Compared to lymphoepithelioma-like carcinoma of the uterine cervix, gastric cancers expressed CLDN18, EPCAM, REG4, BBC3, OLFM4, PPARG, and CDH17 while they had diminished levels of IFITM1 and HIF1A. The druggable targets ERBB2 (Her2), MET, and the HIF pathway, as well as several other potential pharmacogenetic indicators (including EBV infection itself, as well as SPARC, TYMS, FCGR2B and REG4) were identified in some tumor specimens. Conclusion This study shows how modern molecular technology applied to archival fixed tissues yields novel insights into viral oncogenesis that could be useful in managing affected patients. | ||
650 | 4 | |a Gastric adenocarcinoma |7 (dpeaa)DE-He213 | |
650 | 4 | |a Epstein-barr virus |7 (dpeaa)DE-He213 | |
650 | 4 | |a RNA expression profile |7 (dpeaa)DE-He213 | |
650 | 4 | |a Stromal cells |7 (dpeaa)DE-He213 | |
650 | 4 | |a Pharmacogenetic test |7 (dpeaa)DE-He213 | |
700 | 1 | |a Morgan, Douglas R |4 aut | |
700 | 1 | |a Meyers, Michael O |4 aut | |
700 | 1 | |a Dominguez, Ricardo L |4 aut | |
700 | 1 | |a Martinez, Enrique |4 aut | |
700 | 1 | |a Kakudo, Kennichi |4 aut | |
700 | 1 | |a Kuan, Pei Fen |4 aut | |
700 | 1 | |a Banet, Natalie |4 aut | |
700 | 1 | |a Muallem, Hind |4 aut | |
700 | 1 | |a Woodward, Kimberly |4 aut | |
700 | 1 | |a Speck, Olga |4 aut | |
700 | 1 | |a Gulley, Margaret L |4 aut | |
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10.1186/1750-9378-7-21 doi (DE-627)SPR029520649 (SPR)1750-9378-7-21-e DE-627 ger DE-627 rakwb eng Tang, Weihua verfasserin aut Epstein-barr virus infected gastric adenocarcinoma expresses latent and lytic viral transcripts and has a distinct human gene expression profile 2012 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © Tang et al.; licensee BioMed Central Ltd. 2012. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( Background EBV DNA is found within the malignant cells of 10% of gastric cancers. Modern molecular technology facilitates identification of virus-related biochemical effects that could assist in early diagnosis and disease management. Methods In this study, RNA expression profiling was performed on 326 macrodissected paraffin-embedded tissues including 204 cancers and, when available, adjacent non-malignant mucosa. Nanostring nCounter probes targeted 96 RNAs (20 viral, 73 human, and 3 spiked RNAs). Results In 182 tissues with adequate housekeeper RNAs, distinct profiles were found in infected versus uninfected cancers, and in malignant versus adjacent benign mucosa. EBV-infected gastric cancers expressed nearly all of the 18 latent and lytic EBV RNAs in the test panel. Levels of EBER1 and EBER2 RNA were highest and were proportional to the quantity of EBV genomes as measured by Q-PCR. Among protein coding EBV RNAs, EBNA1 from the Q promoter and BRLF1 were highly expressed while EBNA2 levels were low positive in only 6/14 infected cancers. Concomitant upregulation of cellular factors implies that virus is not an innocent bystander but rather is linked to NFKB signaling (FCER2, TRAF1) and immune response (TNFSF9, CXCL11, IFITM1, FCRL3, MS4A1 and PLUNC), with PPARG expression implicating altered cellular metabolism. Compared to adjacent non-malignant mucosa, gastric cancers consistently expressed INHBA, SPP1, THY1, SERPINH1, CXCL1, FSCN1, PTGS2 (COX2), BBC3, ICAM1, TNFSF9, SULF1, SLC2A1, TYMS, three collagens, the cell proliferation markers MYC and PCNA, and EBV BLLF1 while they lacked CDH1 (E-cadherin), CLDN18, PTEN, SDC1 (CD138), GAST (gastrin) and its downstream effector CHGA (chromogranin). Compared to lymphoepithelioma-like carcinoma of the uterine cervix, gastric cancers expressed CLDN18, EPCAM, REG4, BBC3, OLFM4, PPARG, and CDH17 while they had diminished levels of IFITM1 and HIF1A. The druggable targets ERBB2 (Her2), MET, and the HIF pathway, as well as several other potential pharmacogenetic indicators (including EBV infection itself, as well as SPARC, TYMS, FCGR2B and REG4) were identified in some tumor specimens. Conclusion This study shows how modern molecular technology applied to archival fixed tissues yields novel insights into viral oncogenesis that could be useful in managing affected patients. Gastric adenocarcinoma (dpeaa)DE-He213 Epstein-barr virus (dpeaa)DE-He213 RNA expression profile (dpeaa)DE-He213 Stromal cells (dpeaa)DE-He213 Pharmacogenetic test (dpeaa)DE-He213 Morgan, Douglas R aut Meyers, Michael O aut Dominguez, Ricardo L aut Martinez, Enrique aut Kakudo, Kennichi aut Kuan, Pei Fen aut Banet, Natalie aut Muallem, Hind aut Woodward, Kimberly aut Speck, Olga aut Gulley, Margaret L aut Enthalten in Infectious agents and cancer London : Biomed Central, 2006 7(2012), 1 vom: 28. Aug. (DE-627)51781403X (DE-600)2251117-9 1750-9378 nnns volume:7 year:2012 number:1 day:28 month:08 https://dx.doi.org/10.1186/1750-9378-7-21 kostenfrei Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 7 2012 1 28 08 |
spelling |
10.1186/1750-9378-7-21 doi (DE-627)SPR029520649 (SPR)1750-9378-7-21-e DE-627 ger DE-627 rakwb eng Tang, Weihua verfasserin aut Epstein-barr virus infected gastric adenocarcinoma expresses latent and lytic viral transcripts and has a distinct human gene expression profile 2012 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © Tang et al.; licensee BioMed Central Ltd. 2012. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( Background EBV DNA is found within the malignant cells of 10% of gastric cancers. Modern molecular technology facilitates identification of virus-related biochemical effects that could assist in early diagnosis and disease management. Methods In this study, RNA expression profiling was performed on 326 macrodissected paraffin-embedded tissues including 204 cancers and, when available, adjacent non-malignant mucosa. Nanostring nCounter probes targeted 96 RNAs (20 viral, 73 human, and 3 spiked RNAs). Results In 182 tissues with adequate housekeeper RNAs, distinct profiles were found in infected versus uninfected cancers, and in malignant versus adjacent benign mucosa. EBV-infected gastric cancers expressed nearly all of the 18 latent and lytic EBV RNAs in the test panel. Levels of EBER1 and EBER2 RNA were highest and were proportional to the quantity of EBV genomes as measured by Q-PCR. Among protein coding EBV RNAs, EBNA1 from the Q promoter and BRLF1 were highly expressed while EBNA2 levels were low positive in only 6/14 infected cancers. Concomitant upregulation of cellular factors implies that virus is not an innocent bystander but rather is linked to NFKB signaling (FCER2, TRAF1) and immune response (TNFSF9, CXCL11, IFITM1, FCRL3, MS4A1 and PLUNC), with PPARG expression implicating altered cellular metabolism. Compared to adjacent non-malignant mucosa, gastric cancers consistently expressed INHBA, SPP1, THY1, SERPINH1, CXCL1, FSCN1, PTGS2 (COX2), BBC3, ICAM1, TNFSF9, SULF1, SLC2A1, TYMS, three collagens, the cell proliferation markers MYC and PCNA, and EBV BLLF1 while they lacked CDH1 (E-cadherin), CLDN18, PTEN, SDC1 (CD138), GAST (gastrin) and its downstream effector CHGA (chromogranin). Compared to lymphoepithelioma-like carcinoma of the uterine cervix, gastric cancers expressed CLDN18, EPCAM, REG4, BBC3, OLFM4, PPARG, and CDH17 while they had diminished levels of IFITM1 and HIF1A. The druggable targets ERBB2 (Her2), MET, and the HIF pathway, as well as several other potential pharmacogenetic indicators (including EBV infection itself, as well as SPARC, TYMS, FCGR2B and REG4) were identified in some tumor specimens. Conclusion This study shows how modern molecular technology applied to archival fixed tissues yields novel insights into viral oncogenesis that could be useful in managing affected patients. Gastric adenocarcinoma (dpeaa)DE-He213 Epstein-barr virus (dpeaa)DE-He213 RNA expression profile (dpeaa)DE-He213 Stromal cells (dpeaa)DE-He213 Pharmacogenetic test (dpeaa)DE-He213 Morgan, Douglas R aut Meyers, Michael O aut Dominguez, Ricardo L aut Martinez, Enrique aut Kakudo, Kennichi aut Kuan, Pei Fen aut Banet, Natalie aut Muallem, Hind aut Woodward, Kimberly aut Speck, Olga aut Gulley, Margaret L aut Enthalten in Infectious agents and cancer London : Biomed Central, 2006 7(2012), 1 vom: 28. Aug. (DE-627)51781403X (DE-600)2251117-9 1750-9378 nnns volume:7 year:2012 number:1 day:28 month:08 https://dx.doi.org/10.1186/1750-9378-7-21 kostenfrei Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 7 2012 1 28 08 |
allfields_unstemmed |
10.1186/1750-9378-7-21 doi (DE-627)SPR029520649 (SPR)1750-9378-7-21-e DE-627 ger DE-627 rakwb eng Tang, Weihua verfasserin aut Epstein-barr virus infected gastric adenocarcinoma expresses latent and lytic viral transcripts and has a distinct human gene expression profile 2012 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © Tang et al.; licensee BioMed Central Ltd. 2012. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( Background EBV DNA is found within the malignant cells of 10% of gastric cancers. Modern molecular technology facilitates identification of virus-related biochemical effects that could assist in early diagnosis and disease management. Methods In this study, RNA expression profiling was performed on 326 macrodissected paraffin-embedded tissues including 204 cancers and, when available, adjacent non-malignant mucosa. Nanostring nCounter probes targeted 96 RNAs (20 viral, 73 human, and 3 spiked RNAs). Results In 182 tissues with adequate housekeeper RNAs, distinct profiles were found in infected versus uninfected cancers, and in malignant versus adjacent benign mucosa. EBV-infected gastric cancers expressed nearly all of the 18 latent and lytic EBV RNAs in the test panel. Levels of EBER1 and EBER2 RNA were highest and were proportional to the quantity of EBV genomes as measured by Q-PCR. Among protein coding EBV RNAs, EBNA1 from the Q promoter and BRLF1 were highly expressed while EBNA2 levels were low positive in only 6/14 infected cancers. Concomitant upregulation of cellular factors implies that virus is not an innocent bystander but rather is linked to NFKB signaling (FCER2, TRAF1) and immune response (TNFSF9, CXCL11, IFITM1, FCRL3, MS4A1 and PLUNC), with PPARG expression implicating altered cellular metabolism. Compared to adjacent non-malignant mucosa, gastric cancers consistently expressed INHBA, SPP1, THY1, SERPINH1, CXCL1, FSCN1, PTGS2 (COX2), BBC3, ICAM1, TNFSF9, SULF1, SLC2A1, TYMS, three collagens, the cell proliferation markers MYC and PCNA, and EBV BLLF1 while they lacked CDH1 (E-cadherin), CLDN18, PTEN, SDC1 (CD138), GAST (gastrin) and its downstream effector CHGA (chromogranin). Compared to lymphoepithelioma-like carcinoma of the uterine cervix, gastric cancers expressed CLDN18, EPCAM, REG4, BBC3, OLFM4, PPARG, and CDH17 while they had diminished levels of IFITM1 and HIF1A. The druggable targets ERBB2 (Her2), MET, and the HIF pathway, as well as several other potential pharmacogenetic indicators (including EBV infection itself, as well as SPARC, TYMS, FCGR2B and REG4) were identified in some tumor specimens. Conclusion This study shows how modern molecular technology applied to archival fixed tissues yields novel insights into viral oncogenesis that could be useful in managing affected patients. Gastric adenocarcinoma (dpeaa)DE-He213 Epstein-barr virus (dpeaa)DE-He213 RNA expression profile (dpeaa)DE-He213 Stromal cells (dpeaa)DE-He213 Pharmacogenetic test (dpeaa)DE-He213 Morgan, Douglas R aut Meyers, Michael O aut Dominguez, Ricardo L aut Martinez, Enrique aut Kakudo, Kennichi aut Kuan, Pei Fen aut Banet, Natalie aut Muallem, Hind aut Woodward, Kimberly aut Speck, Olga aut Gulley, Margaret L aut Enthalten in Infectious agents and cancer London : Biomed Central, 2006 7(2012), 1 vom: 28. Aug. (DE-627)51781403X (DE-600)2251117-9 1750-9378 nnns volume:7 year:2012 number:1 day:28 month:08 https://dx.doi.org/10.1186/1750-9378-7-21 kostenfrei Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 7 2012 1 28 08 |
allfieldsGer |
10.1186/1750-9378-7-21 doi (DE-627)SPR029520649 (SPR)1750-9378-7-21-e DE-627 ger DE-627 rakwb eng Tang, Weihua verfasserin aut Epstein-barr virus infected gastric adenocarcinoma expresses latent and lytic viral transcripts and has a distinct human gene expression profile 2012 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © Tang et al.; licensee BioMed Central Ltd. 2012. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( Background EBV DNA is found within the malignant cells of 10% of gastric cancers. Modern molecular technology facilitates identification of virus-related biochemical effects that could assist in early diagnosis and disease management. Methods In this study, RNA expression profiling was performed on 326 macrodissected paraffin-embedded tissues including 204 cancers and, when available, adjacent non-malignant mucosa. Nanostring nCounter probes targeted 96 RNAs (20 viral, 73 human, and 3 spiked RNAs). Results In 182 tissues with adequate housekeeper RNAs, distinct profiles were found in infected versus uninfected cancers, and in malignant versus adjacent benign mucosa. EBV-infected gastric cancers expressed nearly all of the 18 latent and lytic EBV RNAs in the test panel. Levels of EBER1 and EBER2 RNA were highest and were proportional to the quantity of EBV genomes as measured by Q-PCR. Among protein coding EBV RNAs, EBNA1 from the Q promoter and BRLF1 were highly expressed while EBNA2 levels were low positive in only 6/14 infected cancers. Concomitant upregulation of cellular factors implies that virus is not an innocent bystander but rather is linked to NFKB signaling (FCER2, TRAF1) and immune response (TNFSF9, CXCL11, IFITM1, FCRL3, MS4A1 and PLUNC), with PPARG expression implicating altered cellular metabolism. Compared to adjacent non-malignant mucosa, gastric cancers consistently expressed INHBA, SPP1, THY1, SERPINH1, CXCL1, FSCN1, PTGS2 (COX2), BBC3, ICAM1, TNFSF9, SULF1, SLC2A1, TYMS, three collagens, the cell proliferation markers MYC and PCNA, and EBV BLLF1 while they lacked CDH1 (E-cadherin), CLDN18, PTEN, SDC1 (CD138), GAST (gastrin) and its downstream effector CHGA (chromogranin). Compared to lymphoepithelioma-like carcinoma of the uterine cervix, gastric cancers expressed CLDN18, EPCAM, REG4, BBC3, OLFM4, PPARG, and CDH17 while they had diminished levels of IFITM1 and HIF1A. The druggable targets ERBB2 (Her2), MET, and the HIF pathway, as well as several other potential pharmacogenetic indicators (including EBV infection itself, as well as SPARC, TYMS, FCGR2B and REG4) were identified in some tumor specimens. Conclusion This study shows how modern molecular technology applied to archival fixed tissues yields novel insights into viral oncogenesis that could be useful in managing affected patients. Gastric adenocarcinoma (dpeaa)DE-He213 Epstein-barr virus (dpeaa)DE-He213 RNA expression profile (dpeaa)DE-He213 Stromal cells (dpeaa)DE-He213 Pharmacogenetic test (dpeaa)DE-He213 Morgan, Douglas R aut Meyers, Michael O aut Dominguez, Ricardo L aut Martinez, Enrique aut Kakudo, Kennichi aut Kuan, Pei Fen aut Banet, Natalie aut Muallem, Hind aut Woodward, Kimberly aut Speck, Olga aut Gulley, Margaret L aut Enthalten in Infectious agents and cancer London : Biomed Central, 2006 7(2012), 1 vom: 28. Aug. (DE-627)51781403X (DE-600)2251117-9 1750-9378 nnns volume:7 year:2012 number:1 day:28 month:08 https://dx.doi.org/10.1186/1750-9378-7-21 kostenfrei Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 7 2012 1 28 08 |
allfieldsSound |
10.1186/1750-9378-7-21 doi (DE-627)SPR029520649 (SPR)1750-9378-7-21-e DE-627 ger DE-627 rakwb eng Tang, Weihua verfasserin aut Epstein-barr virus infected gastric adenocarcinoma expresses latent and lytic viral transcripts and has a distinct human gene expression profile 2012 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © Tang et al.; licensee BioMed Central Ltd. 2012. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( Background EBV DNA is found within the malignant cells of 10% of gastric cancers. Modern molecular technology facilitates identification of virus-related biochemical effects that could assist in early diagnosis and disease management. Methods In this study, RNA expression profiling was performed on 326 macrodissected paraffin-embedded tissues including 204 cancers and, when available, adjacent non-malignant mucosa. Nanostring nCounter probes targeted 96 RNAs (20 viral, 73 human, and 3 spiked RNAs). Results In 182 tissues with adequate housekeeper RNAs, distinct profiles were found in infected versus uninfected cancers, and in malignant versus adjacent benign mucosa. EBV-infected gastric cancers expressed nearly all of the 18 latent and lytic EBV RNAs in the test panel. Levels of EBER1 and EBER2 RNA were highest and were proportional to the quantity of EBV genomes as measured by Q-PCR. Among protein coding EBV RNAs, EBNA1 from the Q promoter and BRLF1 were highly expressed while EBNA2 levels were low positive in only 6/14 infected cancers. Concomitant upregulation of cellular factors implies that virus is not an innocent bystander but rather is linked to NFKB signaling (FCER2, TRAF1) and immune response (TNFSF9, CXCL11, IFITM1, FCRL3, MS4A1 and PLUNC), with PPARG expression implicating altered cellular metabolism. Compared to adjacent non-malignant mucosa, gastric cancers consistently expressed INHBA, SPP1, THY1, SERPINH1, CXCL1, FSCN1, PTGS2 (COX2), BBC3, ICAM1, TNFSF9, SULF1, SLC2A1, TYMS, three collagens, the cell proliferation markers MYC and PCNA, and EBV BLLF1 while they lacked CDH1 (E-cadherin), CLDN18, PTEN, SDC1 (CD138), GAST (gastrin) and its downstream effector CHGA (chromogranin). Compared to lymphoepithelioma-like carcinoma of the uterine cervix, gastric cancers expressed CLDN18, EPCAM, REG4, BBC3, OLFM4, PPARG, and CDH17 while they had diminished levels of IFITM1 and HIF1A. The druggable targets ERBB2 (Her2), MET, and the HIF pathway, as well as several other potential pharmacogenetic indicators (including EBV infection itself, as well as SPARC, TYMS, FCGR2B and REG4) were identified in some tumor specimens. Conclusion This study shows how modern molecular technology applied to archival fixed tissues yields novel insights into viral oncogenesis that could be useful in managing affected patients. Gastric adenocarcinoma (dpeaa)DE-He213 Epstein-barr virus (dpeaa)DE-He213 RNA expression profile (dpeaa)DE-He213 Stromal cells (dpeaa)DE-He213 Pharmacogenetic test (dpeaa)DE-He213 Morgan, Douglas R aut Meyers, Michael O aut Dominguez, Ricardo L aut Martinez, Enrique aut Kakudo, Kennichi aut Kuan, Pei Fen aut Banet, Natalie aut Muallem, Hind aut Woodward, Kimberly aut Speck, Olga aut Gulley, Margaret L aut Enthalten in Infectious agents and cancer London : Biomed Central, 2006 7(2012), 1 vom: 28. Aug. (DE-627)51781403X (DE-600)2251117-9 1750-9378 nnns volume:7 year:2012 number:1 day:28 month:08 https://dx.doi.org/10.1186/1750-9378-7-21 kostenfrei Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 7 2012 1 28 08 |
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Tang, Weihua @@aut@@ Morgan, Douglas R @@aut@@ Meyers, Michael O @@aut@@ Dominguez, Ricardo L @@aut@@ Martinez, Enrique @@aut@@ Kakudo, Kennichi @@aut@@ Kuan, Pei Fen @@aut@@ Banet, Natalie @@aut@@ Muallem, Hind @@aut@@ Woodward, Kimberly @@aut@@ Speck, Olga @@aut@@ Gulley, Margaret L @@aut@@ |
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Tang, Weihua misc Gastric adenocarcinoma misc Epstein-barr virus misc RNA expression profile misc Stromal cells misc Pharmacogenetic test Epstein-barr virus infected gastric adenocarcinoma expresses latent and lytic viral transcripts and has a distinct human gene expression profile |
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Epstein-barr virus infected gastric adenocarcinoma expresses latent and lytic viral transcripts and has a distinct human gene expression profile Gastric adenocarcinoma (dpeaa)DE-He213 Epstein-barr virus (dpeaa)DE-He213 RNA expression profile (dpeaa)DE-He213 Stromal cells (dpeaa)DE-He213 Pharmacogenetic test (dpeaa)DE-He213 |
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Tang, Weihua Morgan, Douglas R Meyers, Michael O Dominguez, Ricardo L Martinez, Enrique Kakudo, Kennichi Kuan, Pei Fen Banet, Natalie Muallem, Hind Woodward, Kimberly Speck, Olga Gulley, Margaret L |
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epstein-barr virus infected gastric adenocarcinoma expresses latent and lytic viral transcripts and has a distinct human gene expression profile |
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Epstein-barr virus infected gastric adenocarcinoma expresses latent and lytic viral transcripts and has a distinct human gene expression profile |
abstract |
Background EBV DNA is found within the malignant cells of 10% of gastric cancers. Modern molecular technology facilitates identification of virus-related biochemical effects that could assist in early diagnosis and disease management. Methods In this study, RNA expression profiling was performed on 326 macrodissected paraffin-embedded tissues including 204 cancers and, when available, adjacent non-malignant mucosa. Nanostring nCounter probes targeted 96 RNAs (20 viral, 73 human, and 3 spiked RNAs). Results In 182 tissues with adequate housekeeper RNAs, distinct profiles were found in infected versus uninfected cancers, and in malignant versus adjacent benign mucosa. EBV-infected gastric cancers expressed nearly all of the 18 latent and lytic EBV RNAs in the test panel. Levels of EBER1 and EBER2 RNA were highest and were proportional to the quantity of EBV genomes as measured by Q-PCR. Among protein coding EBV RNAs, EBNA1 from the Q promoter and BRLF1 were highly expressed while EBNA2 levels were low positive in only 6/14 infected cancers. Concomitant upregulation of cellular factors implies that virus is not an innocent bystander but rather is linked to NFKB signaling (FCER2, TRAF1) and immune response (TNFSF9, CXCL11, IFITM1, FCRL3, MS4A1 and PLUNC), with PPARG expression implicating altered cellular metabolism. Compared to adjacent non-malignant mucosa, gastric cancers consistently expressed INHBA, SPP1, THY1, SERPINH1, CXCL1, FSCN1, PTGS2 (COX2), BBC3, ICAM1, TNFSF9, SULF1, SLC2A1, TYMS, three collagens, the cell proliferation markers MYC and PCNA, and EBV BLLF1 while they lacked CDH1 (E-cadherin), CLDN18, PTEN, SDC1 (CD138), GAST (gastrin) and its downstream effector CHGA (chromogranin). Compared to lymphoepithelioma-like carcinoma of the uterine cervix, gastric cancers expressed CLDN18, EPCAM, REG4, BBC3, OLFM4, PPARG, and CDH17 while they had diminished levels of IFITM1 and HIF1A. The druggable targets ERBB2 (Her2), MET, and the HIF pathway, as well as several other potential pharmacogenetic indicators (including EBV infection itself, as well as SPARC, TYMS, FCGR2B and REG4) were identified in some tumor specimens. Conclusion This study shows how modern molecular technology applied to archival fixed tissues yields novel insights into viral oncogenesis that could be useful in managing affected patients. © Tang et al.; licensee BioMed Central Ltd. 2012. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( |
abstractGer |
Background EBV DNA is found within the malignant cells of 10% of gastric cancers. Modern molecular technology facilitates identification of virus-related biochemical effects that could assist in early diagnosis and disease management. Methods In this study, RNA expression profiling was performed on 326 macrodissected paraffin-embedded tissues including 204 cancers and, when available, adjacent non-malignant mucosa. Nanostring nCounter probes targeted 96 RNAs (20 viral, 73 human, and 3 spiked RNAs). Results In 182 tissues with adequate housekeeper RNAs, distinct profiles were found in infected versus uninfected cancers, and in malignant versus adjacent benign mucosa. EBV-infected gastric cancers expressed nearly all of the 18 latent and lytic EBV RNAs in the test panel. Levels of EBER1 and EBER2 RNA were highest and were proportional to the quantity of EBV genomes as measured by Q-PCR. Among protein coding EBV RNAs, EBNA1 from the Q promoter and BRLF1 were highly expressed while EBNA2 levels were low positive in only 6/14 infected cancers. Concomitant upregulation of cellular factors implies that virus is not an innocent bystander but rather is linked to NFKB signaling (FCER2, TRAF1) and immune response (TNFSF9, CXCL11, IFITM1, FCRL3, MS4A1 and PLUNC), with PPARG expression implicating altered cellular metabolism. Compared to adjacent non-malignant mucosa, gastric cancers consistently expressed INHBA, SPP1, THY1, SERPINH1, CXCL1, FSCN1, PTGS2 (COX2), BBC3, ICAM1, TNFSF9, SULF1, SLC2A1, TYMS, three collagens, the cell proliferation markers MYC and PCNA, and EBV BLLF1 while they lacked CDH1 (E-cadherin), CLDN18, PTEN, SDC1 (CD138), GAST (gastrin) and its downstream effector CHGA (chromogranin). Compared to lymphoepithelioma-like carcinoma of the uterine cervix, gastric cancers expressed CLDN18, EPCAM, REG4, BBC3, OLFM4, PPARG, and CDH17 while they had diminished levels of IFITM1 and HIF1A. The druggable targets ERBB2 (Her2), MET, and the HIF pathway, as well as several other potential pharmacogenetic indicators (including EBV infection itself, as well as SPARC, TYMS, FCGR2B and REG4) were identified in some tumor specimens. Conclusion This study shows how modern molecular technology applied to archival fixed tissues yields novel insights into viral oncogenesis that could be useful in managing affected patients. © Tang et al.; licensee BioMed Central Ltd. 2012. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( |
abstract_unstemmed |
Background EBV DNA is found within the malignant cells of 10% of gastric cancers. Modern molecular technology facilitates identification of virus-related biochemical effects that could assist in early diagnosis and disease management. Methods In this study, RNA expression profiling was performed on 326 macrodissected paraffin-embedded tissues including 204 cancers and, when available, adjacent non-malignant mucosa. Nanostring nCounter probes targeted 96 RNAs (20 viral, 73 human, and 3 spiked RNAs). Results In 182 tissues with adequate housekeeper RNAs, distinct profiles were found in infected versus uninfected cancers, and in malignant versus adjacent benign mucosa. EBV-infected gastric cancers expressed nearly all of the 18 latent and lytic EBV RNAs in the test panel. Levels of EBER1 and EBER2 RNA were highest and were proportional to the quantity of EBV genomes as measured by Q-PCR. Among protein coding EBV RNAs, EBNA1 from the Q promoter and BRLF1 were highly expressed while EBNA2 levels were low positive in only 6/14 infected cancers. Concomitant upregulation of cellular factors implies that virus is not an innocent bystander but rather is linked to NFKB signaling (FCER2, TRAF1) and immune response (TNFSF9, CXCL11, IFITM1, FCRL3, MS4A1 and PLUNC), with PPARG expression implicating altered cellular metabolism. Compared to adjacent non-malignant mucosa, gastric cancers consistently expressed INHBA, SPP1, THY1, SERPINH1, CXCL1, FSCN1, PTGS2 (COX2), BBC3, ICAM1, TNFSF9, SULF1, SLC2A1, TYMS, three collagens, the cell proliferation markers MYC and PCNA, and EBV BLLF1 while they lacked CDH1 (E-cadherin), CLDN18, PTEN, SDC1 (CD138), GAST (gastrin) and its downstream effector CHGA (chromogranin). Compared to lymphoepithelioma-like carcinoma of the uterine cervix, gastric cancers expressed CLDN18, EPCAM, REG4, BBC3, OLFM4, PPARG, and CDH17 while they had diminished levels of IFITM1 and HIF1A. The druggable targets ERBB2 (Her2), MET, and the HIF pathway, as well as several other potential pharmacogenetic indicators (including EBV infection itself, as well as SPARC, TYMS, FCGR2B and REG4) were identified in some tumor specimens. Conclusion This study shows how modern molecular technology applied to archival fixed tissues yields novel insights into viral oncogenesis that could be useful in managing affected patients. © Tang et al.; licensee BioMed Central Ltd. 2012. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( |
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7.4012203 |