Modern molecular technology now permits clinical grade analysis of multiple pertinent analytes via RNA expression profiling. De vice manufacturers have produced merely sensitive, specific and customizable probe arrays to simultaneously measure multiple RNAs, including non coding RNAs like EBV encoded RNA 1 or 2 that are abundantly expressed in infected tumors. Recent progress in quality assurance strategies have matured to the point that RNA expression profiles are being implemented in clinical laboratory set tings. To be practical in clinical settings, an assay must be applicable to routinely collected specimens such as arch ival, paraffin embedded tissue. In the current study, we measured viral and human gene expression in arch ival gastric cancers and in adjacent mucosa and controls to develop a test systems that might be used to reliably characterize signatures predictive of response to targeted therapy.
A 96 RNA array test system that we dub the Gastrogenus v1 panel was customized to measure per tinent latent and lytic viral RNAs alongside clinically relevant human mRNAs that were previously reported to be 1 gastric cancer specific, 2 indicative of inflam mation, and/or 3 predictive of response to specific med ications. These assays, as well as spiked and endogenous control RNAs, were measured in macrodissected paraf fin sections using the Nanostring nCounter test system. Correlative histologic and molecular studies were done to demonstrate that the test system per formed as expected.
Our findings show that EBV related cancers express more latent and lytic transcripts than were previously recognized, and that infected cancers have unique biologic characteristics compared with un infected cancers. Two major subtypes of cancer were found, implying that gastric cancer early detection strat egies or monitoring Entinostat tests could be tailored to detect the pertinent signatures characterizing major molecular sub types. Finally, pilot data reveals expression of selected viral and cancer related genes in adjacent non malignant mucosa, suggesting a field effect that could be important in cancer development or maintenance. Results Gene expression profiling was performed on a total of 326 tissues including 187 gastric cancers, 17 lymphoe pithelioma like cervical cancers, and 118 matched non malignant mucosa from the same surgical procedure.
After data normalization, a heat map of the 182 tissues having the best quality Temsirolimus 162635-04-3 RNA, as judged by highest average level of four housekeeping RNAs, revealed patterns of gene expression that differed in gas tric versus cervical control tissues. Furthermore, in both the gastric and cervical clusters, malignant and non malignant tissues tended to cluster together, supporting the ability of the nCounter test system to measure clinic ally important biologic features. One group of gastric carcinomas overexpressed virtu ally all of the EBV RNAs.
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