Microarray Analysis of Radioresistance-associated Genes in Esophageal Squamous Cell Carcinoma
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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:ObjectiveTo identify the novel radioresistance-associated genes in esophageal squamous cell carcinoma and build a foundation for the individualized radiotherapy.
MethodsTwo 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.
ResultsMicroarray 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.
ConclusionThe 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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Key words:
- Esophageal squamous cell carcinoma(ESCC) /
- Radiosensitive /
- Radioresistant /
- Microarray
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作者贡献朱青山：立题、主持研究、论文撰写
李军扩：病理资料采集
刘维鹏：病例采集、参考文献搜索
马庭炜：患者资料统计
代宁涛：协助病理资料采集、联系相关公司进行基因检测
冯连杰：课题设计
魏涛：数据分析
周福有：立项及课题指导 -
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图 1 10例食管癌样本中的拷贝数变异（CNV）图示
Figure 1 Compact copy number variance(CNV) in 10 cases of ESCC samples
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图 2 10例食管癌样本中拷贝数变异（CNV）的染色体G带图
Figure 2 Ideogram of CNV in Chromosome G band in 10 cases of ESCC samples
表 1 放射敏感组（S组）和放射抗拒组（R组）患者的一般临床资料（例）
Table 1 Clinical data of radiosensitive (S) and radio-resistant (R) groups (n)
下载: 导出CSV
表 2 放射敏感组（S组）和放射抵抗组（R组）患者的芯片分析结果
Table 2 Gene chip analysis results of radiosensitive (S) and radioresistant (R) groups
下载: 导出CSV
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