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利用全基因组表达谱筛查鼻咽癌分子标志物

Identification of candidate molecular markers for the expression of NPC by Whole Genome expression profiling

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【作者】 周艳宏曾朝阳熊炜李小玲肖岚张文玲武明花曹利李伟芳李桂源

【Author】 Zhou Yan-Hong Zeng Zhao-Yang Xiong Wei Li Xiao-Ling Xiao Lan Zhang Wen-Ling Wu Ming-Hua Cao Li Li Wei-Fang Li Gui-Yuan Cancer Research Institute, Central South University, 410078

【机构】 中南大学肿瘤研究所

【摘要】 为了寻找鼻咽癌的分子标志物,在鼻咽癌全基因组表达谱分析的基础上利用监督聚类方法筛选到的100个鼻咽癌差异表达基因,然后使用Weighted Voting算法最终筛选到 6个基因,包括鼻咽癌上调基因RB1,STMN1,DSP和下调基因SERPINB6,AGTRL1和SYTL2。其6个基因代表的分类预测模型能将鼻咽癌和鼻咽慢性炎症上皮很好的区分开来 (33/34,97.1%的正确率,Fisher’s exact test,p-value= 8.389 × 10-8)。利用RT—PCR方法对其中的SERPINB6 和AGTRL1基因进行验证、证实microarray结果可靠。表明这6个基因的表达可基本代表鼻咽癌的表达特征、为鼻咽癌的候选分子标志物,但其生物学意义有待进一步深入研究。

【Abstract】 In order to identify the candidate molecular markers for the expression of NPC, we sought to refine the NPC-asso-ciated gene expression signature to a small set of genes that reflected the structure of the 100 cDNAs set The weighted voting class prediction models by leave-one-out cross-validation were used. A set of 6 unique genes was chosen for further study because it predicted most accurately NPCs from the nontumor tissues (33 of 34 correct calls; 97.1% accuracy, Fisher’ s exact test, p-value=8.389 × 10-8). Among the 6 genes, two genes controlling the GTP/GDP-bound Ras cycle genes genes (STYL2 and AGTRL1), two genes regulating the cell cycle (RB1 and stmn1), the desmoplakin gene (DSP) and a serine proteinase inhibitor (SERPING6) were included and showed altered expression in the NPC group. To examine the reliability of our microarray data, we selected two down-regulated genes (SERPINB6 and SYTL2) and examined their expression levels by semi-quantitative RT-PCR analysis using the same total RNA samples that had served for the microarray analysis. The results of RT-PCR were consistent with microarray data and demonstrated that these two genes were downexpressed in NPC samples relative to nontumor nasopharyngeal epitheliums. Further studies are needed to investigate the roles these predictor genes in the biologic characteristics and the development of NPC and to identify molecular targets of diagnostic and therapeutic use in nasopharyngeal carcinoma.

【关键词】 鼻咽癌微阵列分子标志物聚类
  • 【会议录名称】 第四届中国肿瘤学术大会暨第五届海峡两岸肿瘤学术会议论文集
  • 【会议名称】第四届中国肿瘤学术大会暨第五届海峡两岸肿瘤学术会议
  • 【会议时间】2006-10
  • 【会议地点】中国天津
  • 【分类号】R739.63
  • 【主办单位】中国抗癌协会、中华医学会肿瘤学分会
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