Comment[ArrayExpressAccession]	E-GEOD-51575
MAGE-TAB Version	1.1									
Public Release Date	2014-03-01
Investigation Title	mRNA Expression Profiling in EBV-postive Gastric Carcinoma and EBV-negative GC in comparison with their normal mucosa tissue									
Comment[Submitted Name]	mRNA Expression Profiling in EBV-postive Gastric Carcinoma and EBV-negative GC in comparison with their normal mucosa tissue
Experiment Description	The better prognosis of patients with Epstein-Barr virus-positive gastric carcinoma than those with EBV-negative GC is correlated with the degree of recruitment of inflammatory tumor infiltrating cells (TIL) to the vicinity of tumor cells. We hypothesized that the better prognosis would associate with less genetic or epigenetic alterations in EBV(+)GC, or EBV infection should deregulate immune modulator proteins, of which secretion recruit TIL. Therefore we performed mRNA expression profilings in EBV(-)GC and EBV(+)GC, each of which was pair wise compared with their normal control. We found that EBV(+)GC had much more molecular homogeneity with focused alterations in immune modulator genes; The Pearson correlation matrix analyses demonstrated that EBV(+)GC tumor showed remarkably high tumor homogeneity. While EBV(-)GC had considerable number genes that are differentially expressed genes from their normal counterparts, EBV(+)GC showed only a handful, almost 20 fold less number of DEG than EBV(-)GC under the same p value cutoff (p<0.001). Gene ontology and pathway analyses showed that while pathways of cation homeostasis, digestion and ion transport were commonly deregulated in both GC types, genes for chromatin assembly, prostaglandin receptor activity, pattern specification process are selectively deregulated in EBV(-)GC tumors. In contrast, pathways or genes for cytokine activity, immune response and lipoprotein particle clearance are selectively deregulated in EBV(+)GC tumors. These results demonstrate that EBV(+)GC inherently evolves to high homogeneity with fewer changes in gene expression and these secret immune modulatory chemokines could recruit reactive immune cells to EBV(+)GC, leading to favorable microenvironment for cancer suppression. All patients underwent the surgery for advanced gastric carcinoma (GC) except one patient with early GC. The EBV-presence in the GC was verified by in situ EBV-encoded small RNA (ERER) staining.. The 14 paired EBV(-)GC patients and 12 paired EBV(+)GC patients were selected for this study. Tumor tissue (T)and normal tissues (N) from distant sites from tumor areas were dissected, frozen at -80C and were subjected to RNA purification, mRNA array profiling analyses.									
Term Source Name	ArrayExpress	EFO
Term Source File	http://www.ebi.ac.uk/arrayexpress/	http://www.ebi.ac.uk/efo/efo.owl								
Person Last Name	Park	Kang	Kim	Park	Kim	Kim	Kim	Choi	Song	Lee
Person First Name	Charny	Myung-Soo	Sun	Charny	Ha-Jung	Kyoung	Sung	Minkyu	Kyung-A	Eun
Person Mid Initials			Y			M				K
Person Email	charn78@gmail.com									
Person Affiliation	Ewha Woman's Univ									
Person Address	Ewha Woman's Univ, Daihyundong, Seoul, South Korea									
Person Roles	submitter									
Protocol Name	P-GSE51575-1	P-GSE51575-3	P-GSE51575-4	P-GSE51575-2	P-GSE51575-5					
Protocol Description	The scanned images were analyzed with Feature Extraction Software 10.7.1.1 (Agilent). Gene expression data analysis was subsequently conducted in R-project (build 2.11.1). The raw data were normalized by using Quantile method. Paired t-test using Algorithm Limma were performed to select differentially expressed genes (DEG) between normal and tumor tissues in EBV(+)GC and EBV(-)GC. DEGs were clustered based by Cluster 3.0 and Tree View software. ID_REF =  VALUE = Normalized signal intensity	See the manufactor's manual (http://www.chem.agilent.com/library/usermanuals/Public/G4140-90040_GeneExpression_OneColor_6.6.pdf). Briefly, total RNA was converted to ds cDNA1 using One-Color Spike Mix. complementary RNA was amplified with T7 promtoer primers and cyanine 3-CTP. Amplified cRNA was purified with Qiagen’s RNeasy mini spin columns and quantified using NanoDrop ND-1000 (Thermo Scientific).	Fragmented cyanine 3-labeled cRNA were loaded on to the gasket slide for hybridization and incubated at 65℃, 10 rpm for 17 hours, See manufactor's manual (http://www.chem.agilent.com/library/usermanuals/Public/G4140-90040_GeneExpression_OneColor_6.6.pdf) for detail	Total RNA was isolated from tissue by using RNeasy Mini Kit (Qiagen, Hilden, Germany). Quantity and quality of isolated RNA were measured by Nanodrop ND-1000 (Thermo Scientific, Waltham, MA).	Microarray slides were scanned on an Agilent C Scanner using the Profile AgilentG3_GX_1Color for 8x60K microarrays.					
Protocol Type	normalization data transformation protocol	labelling protocol	hybridization protocol	nucleic acid extraction protocol	array scanning protocol					
Experimental Factor Name	TUMOR STAGE	HER2+	EBV	SEX	HISTOLOGY	AGE	LAUREN TYPE	ORGANISM PART		
Experimental Factor Type	tumor stage	her2+	ebv	Sex	histology	age	lauren type	organism part		
Comment[SecondaryAccession]	GSE51575									
Comment[GEOReleaseDate]	2014-03-01									
Comment[ArrayExpressSubmissionDate]	2013-10-23									
Comment[GEOLastUpdateDate]	2014-03-01									
Comment[AEExperimentType]	transcription profiling by array									
SDRF File	E-GEOD-51575.sdrf.txt