MRM・MS and microRNA profiling analyses of blood samples and their clinical applications for development of molecular diagnostics

2011 Fiscal Year Final Research Report

• Project/Area Number: 21249037
• Research Category: Grant-in-Aid for Scientific Research (A)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Laboratory medicine
• Research Institution: Nagoya University
• Principal Investigator: TAKAHASHI Takashi 名古屋大学, 大学院・医学系研究科, 教授 (50231395)
• Co-Investigator(Kenkyū-buntansha): YANAGISAWA Kiyoshi 名古屋大学, 大学院・医学系研究科, 講師 (20372112)
• Co-Investigator(Renkei-kenkyūsha): ARIMA Chinatsu 名古屋大学, 大学院・医学系研究科, COE特任助教 (00534843) ; GOTO Hidemi 名古屋大学, 大学院・医学系研究科, 教授 (10215501) ; NAGINO Masato 名古屋大学, 大学院・医学系研究科, 教授 (20237564) ; YATABE Yasushi 愛知県がんセンター, 研究所, 主任研究員 (90280809) ; MATSUO Keitaro 愛知県がんセンター, 研究所, 室長 (80393122)
• Project Period (FY): 2009 – 2011
• Keywords: 分子診断 / 網羅的発現解析 / プロテオミクス / マイクロRNA

Research Abstract

MRM・MS and microRNA profiling analyses of blood samples and their clinical applications for development of molecular diagnostics
We aimed to establish novel molecular diagnostic means for "hard-to-cure "cancers such as pancreatic cancer. We successfully identified four miRNAs present at high levels only in sera of pancreatic cancer patients but not in those of healthy individuals, which allowed us to develop diagnostic classifies for pancreatic cancers based on the expression profiles. In addition, we have successfully catalogued 40, 000 proteins from normal and pancreatic cancer tissues, which should serve as valuable basis for identification of biomarkers of pancreatic cancer. Interestingly, we identified one such protein, high expression of which appeared to confer resistance to endoplasmic reticulum stress in pancreatic cancer.

Research Products

• [Journal Article] MYBPH, atranscriptional target of TTF-1, inhibitsROCK1, and reduces cell motility andmetastasis. (2012)
  • Author(s): Hosono Y, Yamaguchi T, Mizutani E, Yanagisawa K, Arima C, Tomida S, Shimada Y, Hiraoka M, Kato S, Yokoi K, Suzuki M, Takahashi T
  • Journal Title: EMBO J Volume: 31 Pages: 481-493
  • Peer Reviewed
• [Journal Article] A critical role for tumor cell-derived angiopoientin-like protein 2 in metastasis (2012)
  • Author(s): Endo M, Nakano M, Kadomatsu T, Fukuhara S, Kuroda H, Mikami S, Hato T, Aoi J, Horiguchi H, Miyata K, Odagiri H, Masuda T, Harada M, Horio H, Hishima T, Nomori H, Ito T Yamamoto Y, Minami T, Okada S, Takahashi T, Mochizuki N, Iwase H, Oike Y
  • Journal Title: Cancer Res Volume: (in press)
  • Peer Reviewed
• [Journal Article] miR-375 is activated by ASH1 and inhibits YAP1 in a lineage-dependent manner in lung cancer (2011)
  • Author(s): Nishikawa E, Osada H, Okazaki Y, Arima C, Tomida S, Tatematsu Y, Taguchi A, Shimada Y, Yanagisawa K, Yatabe Y, Toyokuni S, Sekido Y, and Takahashi T
  • Journal Title: Cancer Res Volume: 71 Pages: 6165-6173
  • Peer Reviewed
• [Journal Article] Proteasomal non-catalytic subunit PSMD2 as a potential therapeutic target in association with various clinicopathologic features in lung adenocarcinomas (2011)
  • Author(s): Matsuyama, Y., Suzuki, M., Arima, C., Huang, Q. M., Tomida, S., Takeuchi, T., Sugiyama, R., Itoh, Y., Yatabe, Y., Goto, H. and Takahashi, T
  • Journal Title: Mol. Carcinog Volume: 50 Pages: 301-309
  • Peer Reviewed
• [Journal Article] A novel network profiling analysis reveals system changes in epithelial-mesenchymal transition (2011)
  • Author(s): Shimamura, T., Imoto, S., Shimada, Y., Hosono, Y., Niida, A., Nagasaki, M., Yamaguchi, R., Takahashi, T., Miyano, S
  • Journal Title: PLoS ONE Volume: 6 Pages: e20804
  • DOI: doi:10.1371/journal.pone.0020804
  • Peer Reviewed
• [Journal Article] The Epstein-Barr virus LMP 1 and TGF-. 1 synergistically induce EMT in lung epithelial cells. (2011)
  • Author(s): Sides, M., Klingsberg, R. C., Shan, B., Gordon, K. A., Nguyen, H. T., Lin, Z., Takahashi, T., Flemington, E. K., and Lasky, J. A
  • Journal Title: Am. J. Resp. Cell Mol. Biol Volume: 44 Pages: 852-862
  • Peer Reviewed
• [Journal Article] Inhibition of cell survival, invasion, tumor growth and histone deacetylase activity by the dietary flavonoid luteolin in human epithelioid cancer cells (2011)
  • Author(s): Attoub S, Hassan AH, Vanhoecke B, Iratni R, Takahashi T, Gaben AM, Bracke M, Awad S, Kamalboor JA, Al Sultan MAH, Arafat K, Gespach C and Petroianu G
  • Journal Title: Eur. J. Pharmacol Volume: 651 Pages: 18-25
  • Peer Reviewed
• [Journal Article] Mechanisms of amiodarone and desethylamiodarone cytotoxicity in non-transformed human peripheral lung epithelial cells (2011)
  • Author(s): Mulder, J. E., Brien, J. F., Racz, W. J., Takahashi, T. and Massey, T
  • Journal Title: Exp. Ther Volume: 336 Pages: 551-559
  • Peer Reviewed
• [Journal Article] International Association for the Study of Lung Cancer/Amerian Thoracic Society/European Respiratory Society International Multidisciplinary Classification of lung adenocarcinoma (2011)
  • Author(s): Travis WD, Brambilla E, Noguchi M, Nicholson AG, Geisinger KR, Yatabe Y, Beer DG, Powell CA, Eiely GJ, Van Schil PE, Garg, K, Austin JHM, Asamura H, Rusch, VW, Hirsch FR, Scagliotti G, MisudomiT, Huber RM, Ishikawa Y, Jett, J, Sanchez-Cespedes, M, Sculier, JP, Takahashi T, Tsuboi, M, Vansteenkiste J, Wistuba I, Yang, P-C, Aberle D, Brambilla C, Flieder D, Franklin W, Johnson B, Johnson D, Kerr K, Kuriyama K, Lee JS, Miller VA, pertersen I, Roggli V, Rosell R, Saijo N, Thunnissen E, Tsao M, Yankelewitz D
  • Journal Title: J Thorac. Oncol Volume: 6 Pages: 244-285
  • Peer Reviewed
• [Journal Article] Novel metastasis-related gene CIM functions in the regulation of multiple cellular stress response pathways (2010)
  • Author(s): Yanagisawa K, Konishi H, Arima C, Tomida S, Takeuchi T, Shimada Y, Yatabe Y, Mitsudomi T, Osada H, and Takahashi T
  • Journal Title: Cancer Res Volume: 70 Pages: 9949-58
  • Peer Reviewed
• [Journal Article] Functions of base selection step in human DNA polymerase alpha (2010)
  • Author(s): Tanaka, S., Cao, K., Niimi, A., Limsirichaikul, S., Huang, Q., Nakamura, N., Murate, T., Hasegawa, Y., Takahashi, T. and Suzuki M.
  • Journal Title: DNA Repair Volume: 9 Pages: 534-541
  • Peer Reviewed
• [Journal Article] Regulation of DNA polymerase POLD4 influences genomic instability in lung cancer (2010)
  • Author(s): Huang, Q. A., Tomida, S., Masuda, Y., Arima, C., Cao, K, Kisahara, T., Osada, H., Yatabe, Y., Kamiya, K., Takahashi, T., and Suzuki, M
  • Journal Title: Cancer Res Volume: 70 Pages: 8407-8416
  • Peer Reviewed
• [Journal Article] Roles of POLD4, smallest subunit of DNA polymeraseδin nuclear structures and genomic stability of human cells (2010)
  • Author(s): Huang, Q. A., Akashi, T., Matsuda, Y., Kamiya, K., Takahashi, T. and Suzuki, M
  • Journal Title: Biophys. Res. Comm Volume: 391 Pages: 542-546
  • Peer Reviewed
• [Journal Article] Homozygous deletion of CDKN2A/2B is a hallmark of iron-induced high-grade rat mesothelioma (2010)
  • Author(s): Hu Q, Akatsuka S, Yamashita Y, Ohara H, Nagai H, Okazaki Y, Takahashi T, and Toyokuni S
  • Journal Title: Lab. Invest Volume: 90 Pages: 360-373
  • Peer Reviewed
• [Journal Article] Endogenous angiogenesis inhibitor vasohibin1 exhibits a broad-spectrum anti-lymphangiogenic activity and suppresses lymph node metastasis (2010)
  • Author(s): Heishi, T., Hosaka, T., Suzuki, H., Suzuki, Y., Miyashita, H., Oike, Y., Takahashi, T., Nakamura, T., Arioka, S., Mitsuda, Y., Takakura, T., Hojo, K., Matsumoto, M., Yamauchi, C., Ohta, H., Sonoda, H., and Sato, Y
  • Journal Title: Am. J. Pathol Volume: 176 Pages: 1950-1958
  • Peer Reviewed
• [Journal Article] Tetraspanin CD151 regulates TGF-βsignalling : implication in tumour metastasis (2010)
  • Author(s): Sadej R, Romanska H, Kavanagh D, Baldwin G, Takahashi T, Kalia N, Berditchevski F
  • Journal Title: Cancer Res Volume: 70 Pages: 6059-6070
  • Peer Reviewed
• [Journal Article] Neurotensin receptor 1 determines the outcome of non-small cell lung cancer (2010)
  • Author(s): Alifano, M., Souaze, F., Dupouy, S., Camilleri-Broet, S., Takahashi, T., Ahmed-Zaid, S., Cancellieri, A., Damiani, S., Boaron, M., Broet, P., Miller, L. D., Gespach, G., Regnard, J. F., and Forgez, P
  • Journal Title: Clin. Cancer Res Volume: 16 Pages: 4401-4410
  • Peer Reviewed
• [Journal Article] Clinically relevant characterization of lung adenocarcinoma subtypes based on cellular pathways (2010)
  • Author(s): Bryant, C. M., Albertus, D. L., Kim, S., Guedj, M., Travis, W. D., Yatabe, Y., Takahashi, T., Brambilla, E, and Beer, D. G
  • Journal Title: PLoS One Volume: 5 Pages: e11712
  • DOI: doi:10.1371/journal.pone.0011712
  • Peer Reviewed
• [Journal Article] Variation in TP63 is associated with lung adenocarcinoma susceptibility in Japanese and Korean populations (2010)
  • Author(s): Miki, D., Kubo, M., Takahashi, A., Yoon, K.-A., Kim, J., Lee, G. K., Zo, J. I., Lee, J. S., Hosono, N., Morizono, T., Tsunoda, T., Kamatani, N., Chayama, K., Takahashi, T., Inazawa, J., Nakamura, Y., and Daigo, Y
  • Journal Title: Nature Genet Volume: 42 Pages: 893-896
  • Peer Reviewed
• [Journal Article] Relapse-related molecular signature in lung adenocarcinomas identifies patients with dismal prognosis (2009)
  • Author(s): Tomida, S., Takeuchi, T., Shimada, Y., Arima, C., Matsuo, K., Mitsudomi, T., Yatabe, Y., and Takahashi, T
  • Journal Title: Clin. Oncol Volume: 27 Pages: 2793-2799
  • Peer Reviewed
• [Journal Article] Relationship of deregulated signaling converging onto mTOR with prognosis and classification of lung adenocarcinoma shown by two independent in silico analyses (2009)
  • Author(s): Ebi, H., Tomida, S., Takeuchi, T., Arima, C., Sato, T., Mitsudomi, T., Yatabe, Y., Osada, H., and Takahashi, T
  • Journal Title: Cancer Res Volume: 69 Pages: 4027-2035
  • Peer Reviewed
• [Journal Article] Counterbalancing influence of miR-17-92 overexpression on adverse effects of RB inactivation in lung cancers (2009)
  • Author(s): Ebi, H., Sato, T., Sugito, N., Hosono, Y., Suzuki, M., Yamaguchi, T., Yatabe, Y., Osada, H., and Takahashi, T
  • Journal Title: Oncogene Volume: 28 Pages: 3371-3379
  • Peer Reviewed
• [Journal Article] PCNA Mono-ubiquitination and activation of translesion DNA polymerases by DNA polymeraseα (2009)
  • Author(s): Suzuki M, Niimi A, Limsirichaikul S, Tomida S, Huang QM, Izuta S, Usukura J, Itoh Y, Hishida T, Akashi T, Nakagawa Y, Kikuchi A, Pavlov Y, Murate T, and Takahashi T
  • Journal Title: J. Biochem Volume: 146 Pages: 13-21
  • Peer Reviewed
• [Journal Article] Neuroendocrine cancer-specific up-regulating mechanism of insulin-like growth factor binding protein-2 in small cell lung cancer (2009)
  • Author(s): Yazawa, T., Sato, H., Shimoyamada, H., Okudela, K., Woo, H., Tajiri, M., Ogura, T., Ogawa, N., Suzuki, T., Mitsui, H., Ishii, J., Miyata, C., Sakaeda, M., Goto, K., Kashiwagi, K., Masuda, M., Takahashi, T., and Kitamura, H
  • Journal Title: Am. J. Pathol Volume: 175 Pages: 976-987
  • Peer Reviewed
• [Journal Article] Down-regulation of DUSP6 expression in lung cancers : its mechanism and potential role in carcinogenesis (2009)
  • Author(s): Okudera, K., Yazawa, T., Woo, T., Sakaeda, M., Ishii, J., Mitsui, H., Tajiri, M., Ogawa, N., Masuda, M., Takahashi, T., Sugimura H., and Kitamura, H
  • Journal Title: Am. J. Pathol Volume: 175 Pages: 867-881
  • Peer Reviewed
• [Journal Article] A bone metastasis model with osteolytic and osteoblastic properties of human lung cancer ACC-LC-319/bone 2 in natural killer cell-depleted severe combined immunodeficient mice (2009)
  • Author(s): Otsuka, S., Hanibuchi, M., Ikuta, K., Yano, S., Goto, H., Ogino, H., Yamada, T., Kakiuchi, S., Nishioka, Y., Takahashi, T., and Sone, S
  • Journal Title: Oncol. Res Volume: 17 Pages: 581-591
  • Peer Reviewed
• [Journal Article] NKX2-1/TITF1/TTF-1-induced ROR1 is required to sustain EGFR survival signaling in lung adenocarcinoma
  • Author(s): Yamaguchi T, Yanagisawa K, Sugiyama R, Hosono Y, ShimadaY, Arima C, Kato S, Tomida S, Suzuki M, Osada H, Takahashi T
  • Journal Title: Cancer Cell Volume: (in press)
  • Peer Reviewed
• [Presentation] Metastasis-suppressing MYBPH as a novel transcriptional target of TTF-1 lineage-survival oncogene in lung adenocarcinoma (2011)
  • Author(s): Takahashi, T
  • Organizer: US-Japan Cancer Genomics Workshop
  • Place of Presentation: Kyoto, Japan
  • Year and Date: 20111024-26
• [Presentation] miRNA alterations in the pathogenesis of human lung cancer (2011)
  • Author(s): Takahashi, T
  • Organizer: The 8th Nikko International Symposium
  • Place of Presentation: Shimotsuke, Japan
  • Year and Date: 2011-10-21
• [Presentation] MicroRNA alterations in the pathogenesis of lung cancers (2010)
  • Author(s): Takahashi, T
  • Organizer: 8th AACR-JCA Joint Conference
  • Place of Presentation: Waikoloa, USA
  • Year and Date: 20100205-09
• [Presentation] MicroRNA alterations in the pathogenesis of lung cancers (2010)
  • Author(s): Takahashi, T
  • Organizer: 1st AACR-IASLC Joint Conference : Molecular Origins of Lung Cancer : Prospects for Personalized Prevention and Therapy
  • Place of Presentation: San Diego, USA
  • Year and Date: 20100111-14
• [Presentation] MicroRNA alterations in the pathogenesis of lung cancers (2009)
  • Author(s): Takahashi, T
  • Organizer: Japanese-German Cancer Workshop
  • Place of Presentation: Hamburg, Germany
  • Year and Date: 20090916-19
• [Presentation] Expression profiling-based approaches for a better understanding of human lung cancer biology (2009)
  • Author(s): Takahashi, T
  • Organizer: 13th World Conference on Lung Cancer, IASLC
  • Place of Presentation: San Francisco, USA
  • Year and Date: 20090731-0804
• [Presentation] Multi-facetted approach for the molecular dissection of lung cancer pathogenesis (2009)
  • Author(s): Takahashi, T
  • Organizer: Hiroshima Cancer Seminar
  • Place of Presentation: Hiroshima, Japan
  • Year and Date: 2009-11-01
• [Remarks] ホームページ
  • URL: http://www.med.nagoya-u.ac.jp/molcar/jp/research.html