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

2013 Fiscal Year Final Research Report

• Project/Area Number: 23390326
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Digestive surgery
• Research Institution: National Center of Neurology and Psychiatry (2012-2013); Kagawa University (2011)
• Principal Investigator: YACHIDA Shinichi 独立行政法人国立がん研究センター, 研究所, ユニット長 (20359920)
• Co-Investigator(Renkei-kenkyūsha): IACOBUZIO-DONAHUE Ca Memorial Sloan Kettering Cancer Center, 病理学, 教授
• Project Period (FY): 2011-04-01 – 2014-03-31
• Keywords: 膵臓癌 / プロテオーム

Research Abstract

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.

Research Products

• [Journal Article] Heterogeneity of pancreatic cancer metastases in a single patient revealed by quantitative proteomics (2014)
  • Author(s): Kim MS, Zhong Y, Y achida S, Rajeshkumar NV, Abel ML, Marimuthu A, Mudgal K, Hruban RH, Poling JS, Tyner JW, Maitra A, Iacobuzio-Donahue CA, Pandey A
  • Journal Title: Mol Cell Proteomics Volume: (in press)
  • Peer Reviewed
• [Journal Article] Immunohistochemically detected expression of three major genes (CDKN2A/p16, TP53 and SMAD4/DPC4) strongly predicts survival in patients with pancreatic cancer (2013)
  • Author(s): Oshima M, Okano K, Muraki S, Haba R, Maeba T, Suzuki Y, Yachida S
  • Journal Title: Ann Surg Volume: 258 Pages: 336-346
  • DOI: 10.1097/SLA.0b013e3182827a6
  • Peer Reviewed
• [Journal Article] (2013)
  • Author(s): Yachida S, Iacobuzio-Donahue CA
  • Journal Title: Oncogene Volume: 32 Pages: 5253-5260
  • DOI: 10.1038/onc.2013.29
  • Peer Reviewed
• [Journal Article] Clinicopathology of recurrent hepatocellular carcinomas after radiofrequency ablation treated with salvage surgery (2013)
  • Author(s): Yamamoto N, Okano K, Kushida Y, Deguchi A, Yachida S, Suzuki Y
  • Journal Title: Hepatol Res
  • DOI: 10.1111/hepr.12223
  • Peer Reviewed
• [Journal Article] Clinical significance of the genetic landscape of pancreatic cancer and implications for identification of potential long-term survivors (2012)
  • Author(s): 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
  • Journal Title: Clin Cancer Res Volume: 18 Pages: 6339-47
  • DOI: 10.1158/1078-0432.CCR-12-1215
  • Peer Reviewed
• [Journal Article] Novel therapeutic approaches in pancreatic cancer based on genomic alterations (2012)
  • Author(s): Yachida S
  • Journal Title: Curr Pharm Des Volume: 18 Pages: 2452-2463
  • Peer Reviewed