Coordinated co expression of multiple viral genes argues that the expression is true positive. Our microarray results raise the possibility that the viral RNAs we detected are not encoding proteins or AZD-2281 that the proteins are 1 only transiently expressed, 2 rapidly degraded, 3 localized to rare cells that are promptly recognized and destroyed by the immune system, or 4 present at such low level that traditional assays are too insensitive to de tect them. The nCounter test system manufacturer claims analytic sensitivity equivalent to that of rtPCR. While most viral genes were expressed almost exclu sively in the infected gastric cancer cohort, EBER1 and EBER2 were commonly expressed in each one of the be nign and malignant gastric and cervical cohorts, albeit at much lower levels than was seen in each of the EBV infected gastric cancers.

Indeed, our study revealed a novel way to identify EBV infected gastric cancer by measuring EBER1 and/or EBER2 RNA in archival tissue, and we have proposed thresholds that successfully dis tinguish infected from uninfected gastric cancer. Support for active viral infection in infected gastric cancer patients comes from serologic evidence of higher titers against viral capsid antigen compared to EBV negative gastric cancer patients and benign controls. Low level lytic infection was previously described in mucosal lymphoid cells and in infected gas tric epithelial cell lines. BARF1 is known to be expressed in gastric cancer where it is proposed to act as a latent rather than a lytic factor.

Using sensitive rtPCR technology, multiple EBV lytic transcripts were detected by Luo et al in gastric cancer tissues. Whether active replicative infection occurs in Dacomitinib malignant epithelial cells or in lymphoid cells remains uncertain since histochemical stains have failed to reveal a cellular source of lytic factors in gastric tissues. While EBV infected gastric cancer is biologically distinct from EBV negative cancer in some respects, the infected counterparts still share many of the classic features previ ously identified as being characteristic of gastric cancer, such as specific collagens, SULF1, THY1, SPP1, INHBA, and SPARC. These selleck Ponatinib pan gastric cancer markers might be exploited for early diag nosis or for monitoring tumor burden during therapy, es pecially when multiple such markers are tested in concert to maximize specificity while still capturing the heterogen eity of the disease. Biomarkers for the EBV infected sub set, such as EBV DNA and the highly expressed viral EBER1, EBER2, EBNA1, and BRLF1 RNAs, as well as asso ciated cellular factors confirmed in this study, represent promising targets for early detection.