Original ResearchFull Report: Basic and Translational—Alimentary TractDeregulation of Immune Response Genes in Patients With Epstein-Barr Virus-Associated Gastric Cancer and Outcomes
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Materials and Methods
The messenger RNA microarray data of normal (N) and tumor (T) pairs from 14 EBVnGC and 12 EBVaGC patients (see Supplementary Table 1 for sample information) were analyzed (Table 1) to list differentially expressed gene (DEG) between EBVnGC and EBVaGC. The results were validated by RNA sequencing of paired ends of whole transcriptome (Hi RNAseq) using Illumina HiSeq 2000 instrument and by real-time quantitative polymerase chain reaction (RTqPCR). All materials and methods are described in the
Unsupervised Clustering Analyses Separate Epstein-Barr Virus–Associated Gastric Carcinoma From Epstein-Barr Virus–Nonassociated Gastric Carcinoma
The messenger RNA microarray raw data were corrected by Robust Multi-Array Average and normalized by the quantile method. The box plots before and after plot normalization showed that all data were normalized to present almost equal median and quantile fraction (deposited as GSE51575 in GEO) (Supplementary Figure 1A). Hierarchical clustering distinguished tumors from normal tissues and also EBVaGC from EBVnGC with a few outliers (Supplementary Figure 1B). An unsupervised fuzzy clustering and
Discussion
Both EBVnGC and EBVaGC are subclassified into 3 subtypes, LELC, carcinoma with Crohn's disease-like lymphoid reaction, and conventional-type adenocarcinoma, based on the degree of infiltration of immune cells and the extent of desmoplasia regardless of EBV infection. Among EBVaGC patients, those with the LELC subtype presented the best prognosis, followed by those with Crohn's disease-like lymphoid reaction, which in turn presented better survival than those with conventional-type
Acknowledgments
The messenger RNA microarray and RNAseq data were deposited as GSE51575 and GSE60873, respectively, in GEO.
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Conflicts of interest The authors disclose no conflicts.
Funding This study was supported by Samsung Biomedical Research Institute (SMX1132731, SMX1132461, OB00013). This research was supported by a grant of the Korea Healthcare Technology R&D Project through the Korea Health Industry Development Institute (KHIDI), funded by the Ministry for Health & Welfare, Republic of Korea. (HI09C1552).
Author names in bold designate shared co-first authorship.
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Authors share co-first authorship.