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食管鳞状细胞癌基因组畸变候选靶基因的鉴定

Identification of candidate target genes of genomic aberrations in esophageal squamous cell carcinoma.

作者信息

Shen Tian-Yun, Mei Li-Li, Qiu Yun-Tan, Shi Zhi-Zhou

机构信息

Faculty of Medicine, Kunming University of Science and Technology, Kunming, Yunnan 650500, P.R. China.

出版信息

Oncol Lett. 2016 Oct;12(4):2956-2961. doi: 10.3892/ol.2016.4947. Epub 2016 Aug 3.

Abstract

The aim of the present study was to identify the candidate target genes of genomic aberrations in esophageal squamous cell carcinoma (ESCC). Array comparative genomic hybridization (CGH) and quantitative polymerase chain reaction were applied to analyze the copy number changes and expression level of candidate genes, respectively. Integrative analysis revealed that homozygous deletions of cyclin-dependent kinase inhibitor (CDKN) 2A and CDKN2B and gains of fascin actin-bundling protein 1 (FSCN1) and homer scaffolding protein 3 (HOMER3) occurred frequently in ESCC. The results demonstrated that the homozygous deletion of CDKN2A or CDKN2B was significantly associated with lymph node metastasis. Notably, the expression of CDKN2A and CDKN2B was lower in dysplasia than in normal esophageal epithelium. We also observed that the copy number increase of FSCN1 was significantly associated with pT, pN and pStage, and that the gain of HOMER3 was significantly linked with pN and pStage. We further revealed that FSCN1 and HOMER3 were overexpressed in ESCC, and that their overexpression was correlated with copy number increase. In conclusion, CDKN2A, CDKN2B, FSCN1 and HOMER3 are candidate cancer-associated genes and may play a tumorigenic role in ESCC.

摘要

本研究的目的是鉴定食管鳞状细胞癌(ESCC)基因组畸变的候选靶基因。分别应用阵列比较基因组杂交(CGH)和定量聚合酶链反应分析候选基因的拷贝数变化和表达水平。综合分析显示,细胞周期蛋白依赖性激酶抑制剂(CDKN)2A和CDKN2B的纯合缺失以及丝状肌动蛋白成束蛋白1(FSCN1)和荷马支架蛋白3(HOMER3)的扩增在ESCC中频繁发生。结果表明,CDKN2A或CDKN2B的纯合缺失与淋巴结转移显著相关。值得注意的是,发育异常中CDKN2A和CDKN2B的表达低于正常食管上皮。我们还观察到,FSCN1的拷贝数增加与pT、pN和p分期显著相关,HOMER3的扩增与pN和p分期显著相关。我们进一步发现,FSCN1和HOMER3在ESCC中过表达,且它们的过表达与拷贝数增加相关。总之,CDKN2A、CDKN2B、FSCN1和HOMER3是候选的癌症相关基因,可能在ESCC中发挥致瘤作用。

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