Genome-wide gene copy number and expression analysis of primary gastric tumors and gastric cancer cell lines.

Genome-wide gene copy number and expression analysis of primary gastric tumors and gastric cancer cell lines.
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DOI:
10.1186/1471-2407-10-73
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发表时间:
2010-03-01
期刊:
影响因子:
3.8
通讯作者:
Monni O
Monni O
中科院分区:
医学2区
文献类型:
--
作者:
Junnila S;Kokkola A;Karjalainen-Lindsberg ML;Puolakkainen P;Monni O

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胃癌是世界范围内最常见的恶性肿瘤之一,也是癌症相关死亡的第二大常见原因。基因拷贝数的改变在胃癌的发生发展中起重要作用,基因拷贝数的改变是癌细胞控制潜在癌基因和抑癌基因表达的主要机制之一。为了突出胃癌中潜在生物学和临床相关性的基因,我们对原发性胃肿瘤和胃癌细胞系中的基因表达和拷贝数水平进行了系统的基于阵列的调查,并使用基于亲和捕获的转录分析(TRAC测定)和实时qRT-PCR验证了结果。整合的微阵列分析揭示了总共256个基因位于获得或丢失的复发区域,并且在其基因表达中具有至少2倍拷贝数相关的变化。使用qRT-PCR或TRAC试验,在总计118份胃样本中验证了其中13种基因(ALPK 2、ASAP 1、CEACAM 5、CYP 3A 4、ENAH、ERBB 2、HHIPL 2、LTB 4 R、MMP 9、PERLD 1、PNMT、PTPRA和OSMR)的表达水平。所有这13个基因在癌组织和非癌组织中均有差异表达(p < 0.05),其中9个(69.2%)基因的拷贝数和基因表达变化之间的相关性得到验证(p < 0.05)。总之,整合基因表达和拷贝数微阵列分析突出了可能对胃癌发生至关重要的基因。TRAC和qRT-PCR分析验证了微阵列结果,因此这些基因作为胃癌潜在生物标志物的作用。
Gastric cancer is one of the most common malignancies worldwide and the second most common cause of cancer related death. Gene copy number alterations play an important role in the development of gastric cancer and a change in gene copy number is one of the main mechanisms for a cancer cell to control the expression of potential oncogenes and tumor suppressor genes. To highlight genes of potential biological and clinical relevance in gastric cancer, we carried out a systematic array-based survey of gene expression and copy number levels in primary gastric tumors and gastric cancer cell lines and validated the results using an affinity capture based transcript analysis (TRAC assay) and real-time qRT-PCR. Integrated microarray analysis revealed altogether 256 genes that were located in recurrent regions of gains or losses and had at least a 2-fold copy number- associated change in their gene expression. The expression levels of 13 of these genes, ALPK2, ASAP1, CEACAM5, CYP3A4, ENAH, ERBB2, HHIPL2, LTB4R, MMP9, PERLD1, PNMT, PTPRA, and OSMR, were validated in a total of 118 gastric samples using either the qRT-PCR or TRAC assay. All of these 13 genes were differentially expressed between cancerous samples and nonmalignant tissues (p < 0.05) and the association between copy number and gene expression changes was validated for nine (69.2%) of these genes (p < 0.05). In conclusion, integrated gene expression and copy number microarray analysis highlighted genes that may be critically important for gastric carcinogenesis. TRAC and qRT-PCR analyses validated the microarray results and therefore the role of these genes as potential biomarkers for gastric cancer.
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