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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

超声内镜引导下细针穿刺活检标本分析胰腺癌化疗敏感性与基因表达谱的关系并应用于临床

基本信息

批准号：
14570447
负责人：
TADA Minoru
金额：
$ 2.18万
依托单位：
The University of Tokyo
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2002
资助国家：
日本
起止时间：
2002 至 2004
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-14570447/
关键词：
Pancreatic carcinoma Chemo-sensitivity Gemcitabine Microarray Drug resistance Endoscopic ultrasonography

项目摘要

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.

我们利用基因芯片技术分析了人胃肠道癌和肝癌细胞的化疗敏感性与基因表达谱之间的关系，并通过构建相关网络对数据进行了分析。胰腺癌在诊断时通常是不可切除的，使用吉西他滨的化疗现在是晚期胰腺癌的标准治疗。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）在两种检测中均与吉西他滨敏感性相关。我们正在尝试分析通过内窥镜超声引导细针抽吸活检获得的标本中的这6个基因，并将检查基因谱与临床之间的关系吉西他滨化疗的结局。