原发性胃肿瘤和胃癌细胞系的全基因组基因拷贝数和表达分析。

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

机构信息

Institute of Biomedicine, Medical Biochemistry and Developmental Biology, Genome-Scale Biology Research Program, University of Helsinki, Helsinki, Finland.

出版信息

BMC Cancer. 2010 Mar 1;10:73. doi: 10.1186/1471-2407-10-73.

DOI:10.1186/1471-2407-10-73

PMID:20187983

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC2837868/

Abstract

BACKGROUND

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.

METHODS

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.

RESULTS

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).

CONCLUSION

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.

摘要

背景

胃癌是全球最常见的恶性肿瘤之一，也是癌症相关死亡的第二大主要原因。基因拷贝数改变在胃癌的发生发展中起着重要作用，基因拷贝数的改变是癌细胞控制潜在癌基因和肿瘤抑制基因表达的主要机制之一。

方法

为了突出胃癌中具有潜在生物学和临床相关性的基因，我们对原发性胃癌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。

结果

综合微阵列分析显示，共有 256 个基因位于增益或缺失的重现区域，其基因表达的拷贝数相关变化至少有 2 倍。这些基因中的 13 个基因（ALPK2、ASAP1、CEACAM5、CYP3A4、ENA H、ERBB2、HHIPL2、LTB4R、MMP9、PERLD1、PNMT、PTPRA 和 OSMR）的表达水平在总共 118 个胃癌样本中使用 qRT-PCR 或 TRAC 测定进行了验证。这 13 个基因在癌症样本和非恶性组织之间的表达水平均有差异（p<0.05），并且对于其中的 9 个基因（69.2%）验证了拷贝数和基因表达变化之间的相关性（p<0.05）。