Verification of diagnostic biomarker candidates for biliary and pancreatic carcinoma by SRM MS-based Multiple Assay

通过基于 SRM MS 的多重检测验证胆管癌和胰腺癌的候选诊断生物标志物

• 批准号: 19689028
• 负责人: ONOGAWA Tohru
• 金额: $ 11.32万
• 依托单位: Tohoku University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Young Scientists (A)
• 财政年份: 2007
• 资助国家: 日本
• 起止时间: 2007 至 2010
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-19689028/
• 关键词: 薬物輸送体; 抗癌剤感受性; プロテオミクス; バイオマーカー; 質量分析; トランスポーター; 癌細胞; フォーカス; 薬物輸送; 抗癌剤

Cholangiocarcinoma (CC) is usually diagnosed in advanced stage and associated with a dismal prognosis. A proteomic analysis may help identify novel biomarkers for the eraly detection, prevention and treatment of CC. The purpose of this study was to identify proteins differentially overexpressed in CC and to validate these proteins as potential biomarkers. We conducted a retrospective global proteomic sthdy of formalin-fixed parafiin-embedded (FEPE) tissues by shotgun LC-MS/MS. We identified abouto 2000 proteins, and statistical comparison showed that 160 proteins were overexpressed in CC compared to noncancerous bile duct. We applied a targeted proteomics approach based on selected reaction monitoring (SRM) to quantify a subset of these proteins. SRM analysis suggested that some proteins would be useful as potential biomarkers. Expression of these proteins was cinfirmed by immunohistochemistry. Further validation using a large-scale sample set of FFPE tissues is now under way.

胆管细胞癌(CC)通常诊断为晚期，预后较差。蛋白质组学分析可能有助于识别早期检测、预防和治疗CC的新生物标志物。本研究的目的是鉴定CC中差异过表达的蛋白质，并验证这些蛋白质是否为潜在的生物标记物。我们用鸟枪式LC-MS/MS对福尔马林固定的石蜡包埋(FEPE)组织进行了全程蛋白质组学研究，共鉴定出约2000个蛋白质，统计比较表明，与非癌胆管相比，癌组织中有160个蛋白质过表达。我们应用了一种基于选择性反应监测(SRM)的靶向蛋白质组学方法来量化这些蛋白质的子集。SRM分析表明，一些蛋白质可能是有用的潜在生物标志物。免疫组织化学方法证实这些蛋白的表达。使用大规模FFPE组织样本集的进一步验证目前正在进行中。

项目成果

Advanced bile duct carcinoma in a 15-year-old patient with pancreaticobiliary maijunction and congenital biliary cystic disease

1例患有胰胆管连接处合并先天性胆囊性疾病的15岁晚期胆管癌患者

• 发表时间: 2008
• 期刊: J Hepatobiliary Pancreat Surg. 15(5)
• 作者: Nakamura H;Katayose Y;Rikiyama T;Onogawa T;Yamamoto K;Yoshida H;Hayashi H;Ohtsuka H;Hayashi Y;Egawa S;Unno M
• 通讯作者: Unno M

ホルマリン固定パラフィン包埋(FFPE)組織切片の臨床プロテオーム解析における基礎パラメータの検討

福尔马林固定石蜡包埋 (FFPE) 组织切片临床蛋白质组分析基本参数的检查

• 发表时间: 2010
• 作者: 小野川徹;ら
• 通讯作者: ら

Human liver-specific organic anion transporter-2 is a potent prognostic factor for human breast carcinoma

• DOI: 10.1111/j.1349-7006.2007.00570.x
• 发表时间: 2007-10-01
• 期刊: CANCER SCIENCE
• 影响因子: 5.7
• 作者: Muto, Mitsuhisa;Onogawa, Tohru;Unno, Michiaki
• 通讯作者: Unno, Michiaki

The HMG-CaA reductase inhibitor prevastatin stimulates insulin secretion through organic anion transporter polypeptides

HMG-CaA还原酶抑制剂普伐他汀通过有机阴离子转运蛋白多肽刺激胰岛素分泌

• 发表时间: 2010
• 期刊: Drug Metab Pharmacokinet
• 作者: Abe M;Toyohara T;Ishii A;Suzuki T;Noguchi N;Akiyama Y;Shiwaku HO;Nakagomi-Hagugara R;Zheng G;Shibata E;Souma T;Shindo T;Shima H;Takeuchi Y;Mishima E;Tanemoto M;Terasaki T;Onogawa T;Unno M;Ito S;Takasawa S;Abe T
• 通讯作者: Abe T

肝内結石症における肝内胆管癌の特徴と治療成績

肝内胆管癌合并肝内胆管癌的特点及治疗效果

• 发表时间: 2007
• 期刊: 消化器画像 28(7)
• 作者: Onogawa T;Muto M;Suzuki T;Ishida T;Rikiyama T;Katayose Y;Ohuchi N;Sasano H;Abe T;Unno M.;小野川 徹
• 通讯作者: 小野川 徹