应用基因芯片技术筛查肺癌变相关基因的研究

目的 使用基因芯片技术研究肺鳞癌及化学致癌物诱导入气管上皮细胞恶性转化的癌变相关基因。方法 应用含4096条人类全长基因的cDNA芯片分别检测6例肺鳞癌和6例正常肺组织的基因表达谱；并用上述芯片研究苯并(a)芘代谢产物BPDEanti-Benzo(a)pyrene diolepoxide，BPDE]和结晶型硫化镍所诱导的人支气管上皮细胞恶性转化与正常的人支气管上皮细胞系(16HBE)在基因表达谱上的差异；将3类标本共同的差异表达基因确定为肺癌变的相关基因。结果 在肺鳞癌／正常肺组织之间、BPDE诱导的恶性转化细胞／正常16HBE细胞之间及硫化镍诱导的恶性转化细胞/正常16HBE细胞之间发现差异表达基因分别为171条、143条和151条。通过比较，发现89条与肺癌变相关的共同基因，其中表达显著增加的基因39条，它们是：癌基因6条；细胞周期相关基因4条；细胞增殖基因6条；肿瘤转移基因8条；神经内分泌基因3条；耐药基因1条；凋亡抑制基因1条；氧化基因1条；其他基因9条。表达显著下降的基因50条，它们是：抑癌基因7条；DNA修复基因11条；抗氧化基因1条；GST基因家族3条；细胞骨架基因3条；凋亡诱导基因2条；信号传导基因5条；细胞因子及其受体基因5条；细胞代谢基因7条，细胞外基质基因1条；其他基因5条。结论 cDNA基因芯片技术能有效地研究基因的表达谱，筛查出肺癌变相关基因。

Study on lung carcinogenesis associated genes in human lung squamous cell carcinoma and malignant transformation of human bronchial epithelial cells induced by carcinogen

Objective To investigate lung carcinogenesis associated genes in human lung squamous cell carcinoma and malignant transformation of human bronchial epithelial cells induced by chemical carcinogens with cDNA microarray. Methods The gene expression patterns were detected in all specimens by cDNA microarray which representing 4 096 different human genes. The differences in gene expression among 6 cases of human lung squamous cell carcinoma tissues and 6 normal lung tissues were analyzed. The different gene expression patterns between the normal human bronchial epithelial cell lines (16HBE) and the malignant transformation of human bronchial epithelial cells induced by Benzo(a)pyrene metabolite BPDE (anti-Benzo(a)pyrene diol-epoxide,BPDE) and crystalline nickel sulfide were also studied by that method. The similar changed genes among those gene expression patterns were identified as lung carcinogenesis associated genes. Results Among the 4096 genes of cDNA microarrays, there were 171 genes expressed differently among lung cancer tissues and normal lungs, 143 genes expressed differently between BPDE transformed cells and normal 16HBE cell lines, 151 genes differed between nickel sulfide transformed cells and normal 16HBE cell lines. By comparing the gene expression profiles, there were 89 similar changed genes which might be associated with human lung carcinogenesis, 39 of which were up regulated: 6 oncogenes, 4 cell cycle control genes, 6 cell proliferation genes, 8 metastasis genes, 3 neuroendocrine genes, 1 drug-resister gene, 1 anti-apoptosis gene, 1 oxidative gene and other 9 genes. 50 genes were down-regulated: 7 tumor suppression genes, 11 DNA repair genes, 1 antioxidant genes, 3 GST family genes, 3 cell framework genes, 2 apoptosis induced genes, 5 signal conduction genes, 5 cytokines and their receptor genes, 7 metabolization genes, 1 cell matrix genes, and other 5 genes. Conclusion cDNA microarray can be applied to study gene expression profiles effectively and to screen human lung carcinogenesis associated genes.