食管癌放射抵抗相关基因的筛选

朱青山; 李军扩; 刘维鹏; 马庭炜; 代宁涛; 冯连杰; 魏涛; 周福有

doi:10.3971/j.issn.1000-8578.2019.18.1007

食管癌放射抵抗相关基因的筛选

Microarray Analysis of Radioresistance-associated Genes in Esophageal Squamous Cell Carcinoma

摘要

摘要:
目的筛选与食管癌放射抵抗相关的基因，为指导临床个体化治疗打下基础。
方法采用基因芯片技术检测放疗疗效差异最大的两组患者之间差异明显的CNV片段，筛选出这些CNV片段中的代表性基因。进一步从筛选出的高度相关的代表性基因中，利用qPCR进行验证。
结果基因芯片筛查的结果得到显著差异的CNV片段共5个，分别位于3、4、8、11、17号染色体，其中拷贝数缺失的（CN Loss）3个，增加的（CN Gain）1个，杂合性缺失的（LOH）1个。代表性基因分别为ROBO1、NSD2、CSMD3、CADM1、NF1。qPCR验证的放射抵抗相关基因为NSD2和CADM1，主要涉及DNA损伤修复通路和细胞黏附。
结论基因芯片筛选食管癌放射抵抗相关分子标记具有可行性。NSD2和CADM1可能是与食管癌放射抵抗的相关位点。

Abstract:
Objective To identify the novel radioresistance-associated genes in esophageal squamous cell carcinoma and build a foundation for the individualized radiotherapy.
Methods Two groups of ESCC patients were selected: radiosensitive group (S) and radioresistant group (R). Copy number variation(CNV) profiles of the selected ESCC tissues were screened using genechip microarray to obtain significant symbolic genes. Furthermore, qPCR analysis was used to confirm the results of the microarray.
Results Microarray assay results showed that the significant differences of CNVs occurred in chromosomes 3, 4, 8, 11 and 17, respectively. The symbolic genes were ROBO1 (CN Loss), NSD2 (CN Loss), CSMD3 (CN Gain), CADM1 (CN Loss) and NF1(LOH). Further, qPCR results demonstrated the radioresistant genes were NSD2 and CADM1 which were related to DNA damage repair and cell adhesion, respectively.
Conclusion The application of genechip microarray technique in CNV profiles screening is a powerful strategy to identify novel radioresistance-associated biomarkers of ESCC. NSD2 and CADM1 may be the radioresistance-associated candidate genes in ESCC.

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