Identification of candidate target genes of genomic aberrations in esophageal squamous cell carcinoma
Identification of candidate target genes of genomic aberrations in esophageal squamous cell carcinoma
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食管鳞状细胞癌基因组畸变候选靶基因的鉴定。
DOI：
10.3892/ol.2016.4947
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发表时间：
2016-10-01
期刊：
影响因子：
2.9
通讯作者：
Shi, Zhi-Zhou
中科院分区：
文献类型：
--
作者：
Shen, Tian-Yun;Mei, Li-Li;Shi, Zhi-Zhou
本研究的目的是确定食管鳞状细胞癌（ESCC）基因组畸变的候选靶基因。应用芯片比较基因组杂交（CGH）和定量聚合酶链反应分别分析候选基因的拷贝数变化和表达水平。综合分析显示，ESCC 中经常发生细胞周期蛋白依赖性激酶抑制剂 (CDKN) 2A 和 CDKN2B 的纯合缺失以及肌成束蛋白肌动蛋白捆绑蛋白 1 (FSCN1) 和荷马支架蛋白 3 (HOMER3) 的增加。结果表明CDKN2A或CDKN2B的纯合缺失与淋巴结转移显着相关。值得注意的是，不典型增生中 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pStage显着相关，并且HOMER3的增加与pN和pStage显着相关。我们进一步发现 FSCN1 和 HOMER3 在 ESCC 中过度表达，并且它们的过度表达与拷贝数增加相关。总之，CDKN2A、CDKN2B、FSCN1和HOMER3是候选癌症相关基因，可能在食管鳞癌中发挥致瘤作用。
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.