Molecular profiling of proprotein convertases toward identification of secreted pro-hormone precursor proteins as novel tumor markers

• Project/Area Number: 26430150
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Tumor diagnostics
• Research Institution: Shizuoka Cancer Center Research Institute
• Principal Investigator: Ohshima Keiichi 静岡県立静岡がんセンター(研究所), その他部局等, 研究員 (10399587)
• Co-Investigator(Kenkyū-buntansha): 寺島 雅典 静岡県立静岡がんセンター(研究所), その他部局等, 研究員 (40197794)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000); Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2015: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2014: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
• Keywords: 腫瘍マーカー / プロホルモン変換酵素 / ELISA / セクレトーム / 培養細胞 / プロテオーム / エクソーム / トランスクリプトーム / プロテオミクス

Outline of Final Research Achievements

Prohormone is a protein precursor to produce a bioactive peptide by processing, in which prohormone convertases (PCs) are involved. Prohormone of gastric releasing peptide (GRP), proGRP, is abundant and stable in blood from small cell lung cancer patients, resulting in development of a tumor marker. The aim of this study is to identify a novel prohormone-derived tumor marker by estimating the processing function of PCs followed by proteomics-based identification of secreted prohormones. Using cancer cell lines derived from various tissues, including lung, stomach, and colon, along with clinical specimens of tumor and matched normal tissue and blood samples, we profiled gene expression, mutation status, and copy number change in 9 PC genes. This dataset is an invaluable resource for further identification of prohormones in the extracellular spaces. Using the dataset profiling all genes, we also clarified genes with amplification-dependent overexpression to predict cancer driver genes.

Research Products

• [Journal Article] Integrated analysis of gene expression and copy number identified potential cancer driver genes with amplification-dependent overexpression in 1,454 solid tumors. (2017)
  • Author(s): Ohshima K, Hatakeyama K, Nagashima T, Watanabe Y, Kanto K, Doi Y, Ide T, Shimoda Y, Tanabe T, Ohnami S, Ohnami S, Serizawa M, Maruyama K, Akiyama Y, Urakami K, Kusuhara M, Mochizuki T, Yamaguchi K
  • Journal Title: Scientific Reports Volume: 7 Issue: 1 Pages: 641-641
  • DOI: 10.1038/s41598-017-00219-3
  • Peer Reviewed / Open Access
• [Journal Article] Comprehensive characterization of genes associated with the TP53 signal transduction pathway in various tumors. (2017)
  • Author(s): Ohnami S, Ohshima K, Nagashima T, Urakami K, Shimoda Y, Saito J, Naruoka A, Hatakeyama K, Mochizuki T, Serizawa M, Ohnami S, Kusuhara M, Yamaguchi K
  • Journal Title: Molecular and Cellular Biochemistry Volume: March Issue: 1-2 Pages: 1-11
  • DOI: 10.1007/s11010-017-2977-1
  • Peer Reviewed / Open Access
• [Journal Article] <b>Next generation sequencing approach for detecting 491 fusion genes from human </b><b>cancer </b> (2016)
  • Author(s): 1.Urakami K, Shimoda Y, Ohshima K, Nagashima T, Serizawa M, Tanabe T, Saito J, Usui T, Watanabe Y, Naruoka A, Ohnami S, Ohnami S, Mochizuki T, Kusuhara M, Yamaguchi K.
  • Journal Title: Biomedical Research Volume: 37 Issue: 1 Pages: 51-62
  • DOI: 10.2220/biomedres.37.51
  • NAID: 130005128377
  • ISSN: 0388-6107, 1880-313X
  • Peer Reviewed / Open Access
• [Journal Article] ProGRP is a possible tumor marker for patients with Ewing sarcoma. (2015)
  • Author(s): 2.Yamaguchi K, Katagiri H, Takahashi M, Ishida Y, Ono A, Takahashi T, Ohshima K, Mochizuki T, Urakami K, Muramatsu K, Kameya T, Ito I, Nakajima T.
  • Journal Title: Biomedical Research Volume: 36 Issue: 4 Pages: 273-277
  • DOI: 10.2220/biomedres.36.273
  • NAID: 130005094139
  • Peer Reviewed / Open Access
• [Journal Article] Exosome-mediated extracellular release of polyadenylate-binding protein 1 in human metastatic duodenal cancer cells. (2014)
  • Author(s): Ohshima K, Kanto K, Hatakeyama K, Ide T, Wakabayashi-Nakao K, Watanabe Y, Sakura N, Terashima M, Yamaguchi K, Mochizuki T.
  • Journal Title: Proteomics Volume: 14 Issue: 20 Pages: 2297-2306
  • DOI: 10.1002/pmic.201300477
  • Peer Reviewed / Open Access
• [Journal Article] <b>Implementation of individualized medicine for cancer patients by multiomics-based analyses—the Project </b><b>HOPE— </b> (2014)
  • Author(s): Yamaguchi K, Urakami K, Ohshima K, Mochizuki T, Akiyama Y, Uesaka K, Nakajima T, Takahashi M, Tamai S, Kusuhara M.
  • Journal Title: Biomedical Research Volume: 35 Issue: 6 Pages: 407-412
  • DOI: 10.2220/biomedres.35.407
  • NAID: 130004903868
  • ISSN: 0388-6107, 1880-313X
  • Peer Reviewed / Open Access
• [Journal Article] Carcinoembryonic antigen-related cell adhesion molecule 4 (CEACAM4) is specifically expressed in medullary thyroid carcinoma cells. (2014)
  • Author(s): Wakabayashi-Nakao K, Hatakeyama K, Ohshima K, Ken Yamaguchi K, Mochizuki T.
  • Journal Title: Biomed Research Volume: 35 Pages: 237-242
  • NAID: 130004678579
  • Peer Reviewed / Open Access
• [Presentation] Cancer driver pathways in 2,000 tumors -integrated analysis of whole exome sequencing and gene expression profiling- (2016)
  • Author(s): 大島啓一、長嶋剛史、畠山慶一、大浪澄子、大浪俊平、下田勇治、田邉智絵、芹澤昌邦、秋山靖人、浦上研一、楠原正俊、望月徹、山口建
  • Organizer: 第75回日本癌学会学術総会
  • Place of Presentation: 横浜
  • Year and Date: 2016-10-06
• [Presentation] Gene expression profiling: a single institution study of 1,000 cancer patients (2015)
  • Author(s): 大島啓一、長嶋剛史、畠山慶一、下田勇治、田邉智絵、大浪澄子、大浪俊平、芹澤昌邦、浦上研一、秋山靖人、楠原正俊、望月徹、山口建
  • Organizer: 第74回日本癌学会学術総会
  • Place of Presentation: 名古屋
  • Year and Date: 2015-10-08
• [Presentation] プロジェクトHOPE（マルチオーミクス解析を用いたがん患者評価）-全遺伝子発現解析- (2014)
  • Author(s): 大島啓一、畠山慶一、中尾香菜子、長嶋剛史、下田勇治、田邉智絵、大浪澄子、大浪俊平、浦上研一、秋山靖人、楠原正俊、望月徹、山口建
  • Organizer: 第73回日本癌学会学術総会
  • Place of Presentation: 横浜
  • Year and Date: 2014-09-25 – 2014-09-27