State Key Laboratory of Medical Genomics and Shanghai Institute of Hematology, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.
BMC Med Genomics. 2012 May 4;5:14. doi: 10.1186/1755-8794-5-14.
BACKGROUND: 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. METHODS: We 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. RESULTS: Obviously, 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. CONCLUSIONS: Taken 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.
背景:为了阐明与拷贝数变化相关的基因表达,我们对 25 对胃组织进行了全基因组拷贝数和表达微阵列分析。
方法:我们应用激光捕获显微切割(LCM)获得微阵列实验的样本,并使用 244K CGH 微阵列和 Human Exon 1.0 ST 微阵列对 DNA 拷贝数和基因表达进行了分析。
结果:明显的是,8q 的增益频率最高(70%),其次是 20q(63%)。我们还鉴定了不同 TNM 分期或胃组织学亚型的胃癌的分子遗传差异。有趣的是,C20orf11 扩增和 20q13.33 的增益几乎将中度分化(MD)胃癌与低分化(PD)型胃癌分开。选择了一组显示基因拷贝数与表达之间相关性的 163 个基因,鉴定出的基因能够在无监督的双向层次聚类中区分匹配的相邻非癌性样本和胃癌样本。对 163 个基因中的 4 个基因(C20orf11、XPO5、PUF60 和 PLOD3)进行定量 RT-PCR 分析,验证了微阵列结果。值得注意的是,一些候选基因(MCM4 和 YWHAZ)及其相邻基因,如 PRKDC、UBE2V2、ANKRD46、ZNF706 和 GRHL2,被基因组异常一致地下调。
结论:总之,我们的结果揭示了不同 TNM 分期或胃组织学亚型的胃癌中不同的染色体区域改变,这有助于研究临床病理分类,并强调了几个有趣的基因作为胃癌的潜在生物标志物。
BMC Med Genomics. 2012-5-4
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