Analysis of relationship between chemo-sensitivity and gene expression profile in pancreatic cancer by using specimen obtained by endoscopic ultrasonography guided fine needle aspiration biopsy for clinical application

我们利用基因芯片技术分析了人胃肠癌和肝癌细胞化疗敏感性与基因表达谱的关系，并通过构建相关网络对数据进行了分析。胰腺癌在诊断时往往不能切除，使用吉西他滨的化疗现在是晚期胰腺癌的标准治疗方法。经常遇到对吉西他滨的获得性耐药导致治疗失败。本研究采用MTT法检测胰腺癌细胞株Panc 1、MIA-PaCa 2、AsPC 1、BxPC 3、KPIN、Su86.86对吉西他滨的敏感性，并通过基因表达谱与吉西他滨敏感性的关系，寻找决定吉西他滨耐药的基因，为克服吉西他滨耐药提供分子靶点。使用含有10，000个基因的cDNA微阵列检测这六个细胞系的基因表达谱。通过比较这些结果，我们确定了30个与吉西他滨敏感性相关的差异表达基因。此外，我们通过长期暴露于吉西他滨的MIA-PaCa-2胰腺癌细胞建立吉西他滨耐药细胞。我们还比较了亲本MIA-PaCa-2和吉西他滨抗性克隆的基因表达谱，并鉴定了6个重叠基因（GPR3，GPRAB，RPS 13，TNFSF 6，PELO，STXBP3）我们试图分析内镜超声引导细针穿刺活检获得的标本中的这6个基因，并将研究基因谱与临床表现之间的关系。吉西他滨化疗的结局。

We have evaluated the relationship between chemo-sensitivity and gene expression profile in human gastrointestinal and hepatic cancer cells, by using cDNA microarray analysis, and analyzed the data by constructing relevance networks.Pancreatic cancer is often unresectable at diagnosis, and chemotherapy using gemcitabine is now the standard treatment for advanced pancreatic cancer. Acquired resistance to gemcitabine resulting in therapeutic failure is often encountered. We sought to identify genes that determine gemcitabine resistance by evaluating the relationship between gene expression profiles and gemcitabine sensitivity to provide molecular targets for overcoming gemcitabine resistance.Gemcitabine sensitivity was examined in six pancreatic cancer cell lines (Panc1, MIA-PaCa2, AsPC1, BxPC3, KPIN, Su86.86) using MTT assay. The gene expression profiles of these six cell lines were examined using cDNA microarray containing 10,000 genes. By comparing these results, 30 genes were identified as differentially expressed genes correlated with gemcitabine sensitivity.In addition, we established gemcitabine-resistant cells by exposing MIA-PaCa-2 pancreatic cancer cells to long-term gemcitabine. We also compared the gene expression profiles between parental MIA-PaCa-2 and gemcitabine-resistant clone, and identified six overlapping genes (GPR3, CRYAB, RPS13, TNFSF6, PELO, STXBP3) correlated with gemcitabine sensitivity in both assays.We are trying to analyze these 6 genes in specimen obtained by endoscopic ultrasonography guided fine needle aspiration biopsy and will examine relationship between the gene profiles and clinical outcome of chemotherapy treated by gemcitabine.