应用基因芯片技术筛选胰腺癌多药耐药相关基因

Selection of genes related to multidrug resistance of pancreatic ductal adenocarcinoma by microarray analysis

目的应用基因芯片技术筛选胰腺导管腺癌(PDAC)获得性多药耐药(MDR)相关基因。方法通过含人类全基因组的寡聚核苷酸基因芯片(Affymetrix HG U133 2.0 plus)筛查人胰腺癌细胞株 SW1990与多药耐药细胞亚株 SW1990/5-FU,SW1990/ADM 和 SW1990/GEM 之间的表达基因差异,并进行生物信息学分析。结果与亲本株 SW1990相比,3株耐药细胞亚株中表达均有差异的基因共有165条;其中上调表达基因43个,下调表达基因122个。差异表达基因的功能分类包括:抗氧化还原、细胞凋亡、细胞周期、信号转导、细胞黏附相关的基因等。聚类分析发现差异基因中的PRDX4簇、TNKS2簇及 CCDC5簇可能与耐药发生密切相关。结论胰腺癌对化疗的多药耐药是复杂的多基因作用的结果。本试验初步建立了胰腺癌多药耐药发生相关的总体基因表达改变图谱,为胰腺癌多药耐药发生机制的研究提供了新的靶点。

Objective To investigate the genes concerning multidrug resistance （MDR） of pancreatic ductal adenocarcinoma with microarray analysis. Methods Gene expression profile of pancreatic cancer cell line SW1990 and resistance subline SW1990/5-FU, SW1990/ADM, SW1990/GEM were screened in two independent replicates using oligonucleotide microarray （Affymetrix HG U133 2.0 plus） which contained 38 500 human genes. And advanced bioinformatics analysis was conducted. Results Totally, 165 genes and expressed sequence tags （ESTs） ,which were seldom reported to be related with drug resistance before,were statistically difference and the fold change was up- or down-regulated at least 2 folds in all 3 resistant sub-lines when compared with SW1990. According gene ontology, the genes related to oxidoreductase activity, apoptosis, cell cycle, signal transduction and cell adhesion might be some epigenetic changes for MDR development. Hierarchical clustering analysis, showed several interesting clusters, namely, TNKS2, PRDX4 and CCDCA. Conclusions MDR of pancreatic cancer is a complicated and multifactorial process. In the present study, a widespread differential gene expression pattern was constructed in PDAC muhidrug resistant cells. Advanced study will provide new targets for MDR research and cast insights into research of the molecular mechanism of MDR.