There was a linear relationship between the amount of EBER1 and EBER2 RNA and the amount of EBV genome. Our previously established cutoff for the level of EBV genome corresponding to localization of virus to malignant cells resulted in 14 cancers being placed in the EBV infected category. The remaining kinase inhibitor Wortmannin gastric cancers were called EBV negative, and among them the highest recorded RNA levels were 174,016 for EBER1 and 27,972 for EBER2. In contrast, among the EBV infected gastric cancers the lowest EBER1 level was 263,589 and the lowest EBER2 level was 140,081. Proposed cutoffs for identifying a tissue as EBV infected are shown in Figure 2. Genes overexpressed in EBV infected versus EBV negative gastric cancer Twenty eight genes were significantly differentially expressed in EBV infected cancers compared to the EBV negative gastric cancers.

Interestingly, all 28 were upregulated rather than downregulated in the infected cancers, and this bias is explained at least in part by our selection of positive rather than negative markers of infection when choosing the RNAs to be profiled for this study. Failure to identify any downregulated genes was still surprising given reports that EBV is associated with a CpG island methylator phenotype and additionally the virus can destabilize cellular mRNAs globally. Among the genes significantly upregulated in infected cancers were all 18 of the EBV RNAs tested, as well as cytomegalovirus pp65. The cytomegalovirus pp65 result is likely to be false positive, as evidenced by absence of another lytic RNA, cytomegalovirus pol, in the EBV infected cancers.

Furthermore, UL83 but not UL54 was expressed in EBV infected but not in EBV negative cell line controls. Another possible Entinostat explanation for false positive viral RNA expression is probe crossreactivity with viral DNA. Nine human RNAs were significantly upregulated in EBV infected compared to EBV negative gastric cancers FCER2, MS4A1, PLUNC, TNFSF9, TRAF1, CXCL11, IFITM1, PPARG, and FCRL3. Genes differentially expressed in gastric cancer compared to non malignant gastrointestinal mucosa Twenty six genes were significantly dysregulated in gastric cancer compared to non malignant gastric mucosa. The human RNAs upregulated in gastric Dorsomorphin BMP cancer were INHBA, SPP1, THY1, SERPINH1, CXCL1, FSCN1, COL1A1, SPARC, COL1A2, PTGS2, BBC3, ICAM1, TNFSF9, MYC, SULF1, SLC2A1, COL3A1, PCNA, and TYMS, while the downregulated RNAs were CDH1, CLDN18, CHGA, PTEN, SDC1 and GAST. The only viral factor that was differentially expressed was BLLF1 which was significantly higher in cancer than in non malignant gastric mucosa. BLLF1 encodes the late viral envelope protein gp350/220, suggesting that virions are significantly more prevalent in cancer than in non malignant gastric tissue.