Abstract
BackgroundTo elucidate gene expression associated with copy number changes, we performed a genome-wide copy number and expression microarray analysis of 25 pairs of gastric tissues.MethodsWe applied laser capture microdissection (LCM) to obtain samples for microarray experiments and profiled DNA copy number and gene expression using 244K CGH Microarray and Human Exon 1.0 ST Microarray.ResultsObviously, gain at 8q was detected at the highest frequency (70%) and 20q at the second (63%). We also identified molecular genetic divergences for different TNM-stages or histological subtypes of gastric cancers. Interestingly, the C20orf11 amplification and gain at 20q13.33 almost separated moderately differentiated (MD) gastric cancers from poorly differentiated (PD) type. A set of 163 genes showing the correlations between gene copy number and expression was selected and the identified genes were able to discriminate matched adjacent noncancerous samples from gastric cancer samples in an unsupervised two-way hierarchical clustering. Quantitative RT-PCR analysis for 4 genes (C20orf11, XPO5, PUF60, and PLOD3) of the 163 genes validated the microarray results. Notably, some candidate genes (MCM4 and YWHAZ) and its adjacent genes such as PRKDC, UBE2V2, ANKRD46, ZNF706, and GRHL2, were concordantly deregulated by genomic aberrations.ConclusionsTaken together, our results reveal diverse chromosomal region alterations for different TNM-stages or histological subtypes of gastric cancers, which is helpful in researching clinicopathological classification, and highlight several interesting genes as potential biomarkers for gastric cancer.
Highlights
To elucidate gene expression associated with copy number changes, we performed a genome-wide copy number and expression microarray analysis of 25 pairs of gastric tissues
DNA copy number variations in gastric cancer The 27 pairs of gastric samples were analyzed by array-based comparative genomic hybridization (aCGH) as shown in Additional file 1: Table S3
We found that 32 genes selected from genes located at 8q11-q24 via a two-sample t-test (P < 0.0001) from 50 gastric tissues were overexpression along with copy number gain and revealed a distinct clustering of the genes overexpressed in gastric cancer samples and underexpressed in matched adjacent noncancerous samples (Figure 5)
Summary
To elucidate gene expression associated with copy number changes, we performed a genome-wide copy number and expression microarray analysis of 25 pairs of gastric tissues. Despite its steady declining trend worldwide, gastric cancer is still the second most common cause of cancer related deaths with 700,000 cases annually [1]. Due to no symptoms at the early stage of gastric cancer, it is often detected at the advanced stage and the prognosis for treatment at that time is poor [2]. Five-year relative survival rates of Gastric cancers can be divided into two main histological subtypes, differentiated and poorly differentiated (PD) adenocarcinomas. The PD adenocarcinomas occur in relatively young individuals and often metastasize to the peritoneum or lymph nodes, resulting in a poor prognosis [5]. Despite the aggressive nature of PD gastric cancer, little is known about the precise mechanisms of carcinogenesis or progression and specific therapeutic targets
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