Comprehensive proteome analysis of pancreatic cancers for understanding the mechanisms of carcinogenesis and cancer metastasis

胰腺癌的全面蛋白质组分析，以了解癌发生和癌症转移的机制

• 批准号: 23390326
• 负责人: YACHIDA Shinichi
• 金额: $ 11.73万
• 依托单位: National Center of Neurology and Psychiatry (2012-2013)Kagawa University (2011)
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 2011
• 资助国家: 日本
• 起止时间: 2011-04-01 至 2014-03-31
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-23390326/
• 关键词: 膵臓癌; プロテオーム; プロテオーム解析; 転移; プロテーム解析; バイオマーカー

Many patients with pancreatic cancer have metastases to distant organs at the time of initial presentation. The goal of this study is to understand the mechanisms of pancreatic cancer metastasis at the proteome level, contributing to create a novel biomarker. To address, we employed a model system in which cells isolated from three sites of metastasis (liver, lung and peritoneum) from a single patient were compared. We used a SILAC-based accurate quantitative proteomic strategy combined with a high resolution mass spectrometry to analyze the total proteome and tyrosine phosphoproteome of each of the metastases. Our data revealed distinct patterns of both overall proteome expression as well as tyrosine kinase activities across the three different metastatic lesions. This heterogeneity is significant because it led to differential sensitivity of the neoplastic cells to small molecule inhibitors targeting various kinases and other pathways.

许多胰腺癌患者在初次就诊时已转移到远处器官。 本研究的目的是从蛋白质组水平了解胰腺癌转移的机制，为建立一种新的生物标志物做出贡献。 为了解决这个问题，我们采用了一个模型系统，其中比较了从单个患者的三个转移部位（肝、肺和腹膜）分离的细胞。 我们使用了SILAC为基础的精确定量蛋白质组学策略结合高分辨率质谱分析的总蛋白质组和酪氨酸磷酸化蛋白质组的每个转移。 我们的数据揭示了在三种不同的转移性病变中，整体蛋白质组表达以及酪氨酸激酶活性的不同模式。 这种异质性是显著的，因为它导致肿瘤细胞对靶向各种激酶和其他途径的小分子抑制剂的不同敏感性。

项目成果

Small cell and large cell neuroendocrine carcinomas of the pancreas are genetically similar and distinct from well-differentiated pancreatic neuroendocrine tumors.

• DOI: 10.1097/pas.0b013e3182417d36
• 发表时间: 2012-02
• 期刊: The American journal of surgical pathology
• 作者: Yachida S;Vakiani E;White CM;Zhong Y;Saunders T;Morgan R;de Wilde RF;Maitra A;Hicks J;Demarzo AM;Shi C;Sharma R;Laheru D;Edil BH;Wolfgang CL;Schulick RD;Hruban RH;Tang LH;Klimstra DS;Iacobuzio-Donahue CA
• 通讯作者: Iacobuzio-Donahue CA

Clinicopathology of recurrent hepatocellular carcinomas after radiofrequency ablation treated with salvage surgery

• DOI: 10.1111/hepr.12223
• 发表时间: 2014-10-01
• 期刊: HEPATOLOGY RESEARCH
• 影响因子: 4.2
• 作者: Yamamoto, Naoki;Okano, Keiichi;Suzuki, Yasuyuki
• 通讯作者: Suzuki, Yasuyuki

Immunohistochemically Detected Expression of 3 Major Genes (CDKN2A/p16, TP53, and SMAD4/DPC4) Strongly Predicts Survival in Patients With Resectable Pancreatic Cancer

• DOI: 10.1097/sla.0b013e3182827a65
• 发表时间: 2013-08-01
• 期刊: ANNALS OF SURGERY
• 影响因子: 9
• 作者: Oshima, Minoru;Okano, Keiichi;Yachida, Shinichi
• 通讯作者: Yachida, Shinichi

Novel therapeutic approaches in pancreatic cancer based on genomic alterations

基于基因组改变的胰腺癌新治疗方法

• 发表时间: 2012
• 期刊: Curr Pharm Des
• 作者: Yachida S;White CM;Naito Y;Zhong Y;Brosnan JA;Macgregor-Das AM;Morgan RA;Saunders T;Laheru DA;Herman JM;Hruban RH;Klein AP;Jones S;V elculescu V;Wolfganag CL;Iacobuzio-Donahue CA;Yachida S
• 通讯作者: Yachida S

Clinical significance of the genetic landscape of pancreatic cancer and implications for identification of potential long-term survivors.

• DOI: 10.1158/1078-0432.ccr-12-1215
• 发表时间: 2012-11-15
• 期刊: Clinical cancer research : an official journal of the American Association for Cancer Research
• 作者: Yachida S;White CM;Naito Y;Zhong Y;Brosnan JA;Macgregor-Das AM;Morgan RA;Saunders T;Laheru DA;Herman JM;Hruban RH;Klein AP;Jones S;Velculescu V;Wolfgang CL;Iacobuzio-Donahue CA
• 通讯作者: Iacobuzio-Donahue CA