【摘要】 目的通过比较肝门部胆管癌与胆总管中下段癌的全基因组表达差异,进一步揭示胆管癌发生、发展的内在分子机制。方法采用含21329条Oligo DNA的人类全基因组寡核苷酸芯片,对3例肝门部胆管癌与正常胆管配对检测差异表达基因,另取4例胆总管中下段癌标本与正常胆管配对检测差异表达基因,通过SAM分析,得到两者间差异表达基因,并采用实时定量RT-PCR验证芯片结果。结果肝门部胆管癌与胆总管中下段癌之间基因表达既存在共性,又存在差异。与正常胆管组织相比,两者共同上调基因244条,共同下调基因399条;而两者差异表达基因共82条(ratio≥2.0或≤0.5)。通过SAM分析(q=0),两者显著差异表达基因共40条,其中上调基因29条,下调基因11条,包括AREG、EPHA2、SPP1、PACE4等。结论高通量的基因芯片技术能够筛选出大量的胆管癌差异表达基因,肝门部胆管癌与胆总管中下段癌的基因表达亦存在着明显的聚类性质差别。更多还原

【Abstract】 Objective To analyze differentially expressed genes between hilar and distal cholangiocarcinoma and to clarify the molecular mechanism of tumorigenesis. Methods Gene-expression profiles of 3 samples of hilar cholangiocarcinoma and 4 samples of distal cholangiocarcinoma were analyzed using oligo microarray containing 21 329 genes. The differentially expressed genes between the two groups were analyzed using the Significance Analysis of Microarrays (SAM) in order to get the specifically differentially expressed genes. The gene expression presence was verified by real-time PCR (RT-PCR). Results A total of 725 genes of cholangiocarcinoma was regulated significantly compared to normal bile duct. Of them, 244 genes were upregulated and 399 genes were downregualted in both groups; on the other hand, 82 gene expressions between hilar and distal cholangiocarcinoma had significant differences (ratio ≥ 2.0 or ≤ 0.5). The SAM analysis showed that 40 genes, including AREG, EPHA2, SPP1, PACE4, and so on, were identified as differentially regulated between the two groups (q=0). Conclusions These data are helpful for a better understanding of the tumorigenesis of cholangiocarcinoma and contribute to the development of diagnostic and therapeutic strategies. The gene expressions between hilar and distal cholangiocarcinoma are significantly different, which suggests that the two tumors have different molecular mechanisms of tumorigenesis.更多还原