Search for salivary metabolome markers for cancer prediction and prognosis detection

• Project/Area Number: 26462860
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Pathobiological dentistry/Dental radiology
• Research Institution: Tsurumi University
• Principal Investigator: Shibata Tatsuya 鶴見大学, 歯学部, 講師 (90323708)
• Co-Investigator(Kenkyū-buntansha): 二藤 彰 鶴見大学, 歯学部, 教授 (00240747) ; 島田 明美 鶴見大学, 歯学部, 講師 (00339813) ; 杉本 昌弘 東京医科大学, 医学部, 教授 (30458963)
• Project Period (FY): 2014-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000); Fiscal Year 2016: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2015: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2014: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
• Keywords: メタボローム / 唾液 / 腫瘍 / 代謝物 / 乳がん / 乳癌

Outline of Final Research Achievements

In this study, we performed salivary metabolome analysis to search for breast cancer specific and highly reliable biomarker. We investigate differential metabolites between breast cancer bearing mice and control mice, and found several candidate markers. In addition, we performed tracer experiments with 13C-glucose, and detected marker candidates highly reproducibly in tissues such as mammary glands, salivary glands, and blood. These results suggested that salivary metabolome analysis may be useful to detect cancer-specific metabolites.

Research Products

• [Journal Article] Possible association of oestrogen and Cryba4 with masticatory muscle tendon-aponeurosis hyperplasia (2018)
  • Author(s): Hayashi Naoki、Sato Tsuyoshi、Kokabu Shoichiro、Usui Michihiko、Yumoto Megumi、Ikami Eiji、Sakamoto Yasushi、Nifuji Akira、Hayata Tadayoshi、Noda Masaki、Yoda Tetsuya
  • Journal Title: Oral Diseases Volume: 印刷中 Issue: 1 Pages: 274-281
  • DOI: 10.1111/odi.12876
  • Peer Reviewed
• [Journal Article] Annexin A5 involvement in bone overgrowth at the enthesis (2018)
  • Author(s): Shimada Akemi, Ideno Hisashi, Arai Yoshinori, Komatsu Koichiro, Wada Satoshi, Yamashita Teruhito, Amizuka Norio, Poschl Ernst, Brachvogel Bent, Nakamura Yoshiki, Nakashima Kazuhisa, Mizukami Hiroaki, Ezura Yoichi, Nifuji Akira
  • Journal Title: Journal of Bone and Mineral Research Volume: 印刷中 Issue: 8 Pages: 1532-1543
  • DOI: 10.1002/jbmr.3453
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Bardet-Biedl Syndrome 3 regulates development of cranial base midline structures. (2017)
  • Author(s): Kawasaki M, Izu Y, Hayata T, Ideno H, Nifuji A, Sheffield VC, Ezura Y, Noda M.
  • Journal Title: Bone Volume: 101 Pages: 179-190
  • DOI: 10.1016/j.bone.2016.11.017
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Essential roles of G9a in cell proliferation and differentiation during tooth development. (2017)
  • Author(s): Taichi Kamiunten, Hisashi Ideno, Akemi Shimada, Yoshinori Arai, Tatsuo Terashima, Yasuhiro Tomooka, Yoshii Nakamura, Kazuhisa Nakashima, Hiroshi Kimura, Yoichi Shinkai, Makoto Takchibana, Akira Nifuji
  • Journal Title: Experimental ell Research Volume: 357 Issue: 2 Pages: 202-210
  • DOI: 10.1016/j.yexcr.2017.05.016
  • Peer Reviewed / Open Access
• [Journal Article] Serum Metabolomic Profiles for Human Pancreatic Cancer Discrimination (2017)
  • Author(s): Takao Itoi, Masahiro Sugimoto, Makoto Sunamura, et al.
  • Journal Title: Int. J. Mol. Sci. Volume: 18 Issue: 4 Pages: 767-778
  • DOI: 10.3390/ijms18040767
  • Peer Reviewed / Open Access
• [Journal Article] Effect of masticatory stimulation on the quantity and quality of saliva and the salivary metabolomic profile. (2017)
  • Author(s): Okuma N, Saita M, Hoshi N, Soga T, Tomita M, Sugimoto M, Kimoto K
  • Journal Title: PLoS One Volume: 12（8） Issue: 8 Pages: e0183109-e0183109
  • DOI: 10.1371/journal.pone.0183109
  • Peer Reviewed / Open Access
• [Journal Article] Global metabolic reprogramming of colorectal cancer occurs at adenoma stage and is induced by MYC (2017)
  • Author(s): Satoh K, Yachida S, Sugimoto M, Oshima M, Nakagawa T, Akamoto S, Tabata S, Saitoh K, Kato K, Sato S, Igarashi K, Aizawa Y, Kajino-Sakamoto R, Kojima Y, Fujishita T, Enomoto A, Hirayama A, Ishikawa T, Taketo MM, Kushida Y, Haba R, Okano K, Tomita M, Suzuki Y, Fukuda S, Aoki M, Soga T.
  • Journal Title: Proc Natl Acad Sci U S A Volume: 114 Issue: 37
  • DOI: 10.1073/pnas.1710366114
  • Peer Reviewed
• [Journal Article] Early gestational maternal low-protein diet diminishes hepatic response to fasting in young adult male mice (2017)
  • Author(s): Sato Noriko、Sudo Katsuko、Mori Masayo、Imai Chihiro、Muramatsu Masaaki、Sugimoto Masahiro
  • Journal Title: Scientific Reports Volume: 7 Issue: 1 Pages: 9812-9812
  • DOI: 10.1038/s41598-017-10380-4
  • Peer Reviewed / Open Access
• [Journal Article] Metabolomic Profiling as a Possible Reverse Engineering Tool for Estimating Processing Conditions of Dry-Cured Hams. (2017)
  • Author(s): Sugimoto M, Obiya S, Kaneko M, Enomoto A, Honma M, Wakayama M, Soga T, Tomita M.
  • Journal Title: J Agric Food Chem. Volume: 18 Issue: 2 Pages: 402-410
  • DOI: 10.1021/acs.jafc.6b03844
  • Peer Reviewed
• [Journal Article] Bardet-Biedl Syndrome 3 regulates development of cranial base midline structures. (2016)
  • Author(s): Kawasaki M, Izu Y, Hayata T, Ideno H, Nifuji A, Sheffield VC, Ezura Y, Noda M.
  • Journal Title: Bone Volume: 89 Pages: 419-430
  • DOI: 10.1016/j.bone.2016.02.017
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Cationized gelatin hydrogels mixed with plasmid DNA induce stronger and more sustained gene expression than atelocollagen at calvarial bone defects in vivo. (2016)
  • Author(s): Komatsu K, Shibata T, Shimada A, Ideno H, Nakashima K, Tabata Y, Nifuji A.
  • Journal Title: J Biomater Sci Polym Ed. Volume: 27 Issue: 5 Pages: 419-430
  • DOI: 10.1080/09205063.2016.1139486
  • Peer Reviewed / Open Access
• [Journal Article] Clinical significance of the expression of autophagy-associated marker, beclin 1, in breast cancer patients who received neoadjuvant endocrine therapy. (2016)
  • Author(s): Ueno T, Saji S, Sugimoto M, Masuda N, Kuroi K, Sato N, Takei H, Yamamoto Y, Ohno S, Yamashita H, Hisamatsu K, Aogi K, Iwata H, Imoto S, Sasano H, Toi M
  • Journal Title: BMC Cancer Volume: 16 Issue: 1 Pages: 230-230
  • DOI: 10.1186/s12885-016-2270-9
  • NAID: 120005973398
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Serum immunoglobulin G Fc region N-glycosylation profiling by matrix-assisted laser desorption/ionization mass spectrometry can distinguish breast cancer patients from cancer-free controls. (2016)
  • Author(s): Kawaguchi-Sakita N, Kaneshiro-Nakagawa K, Kawashima M, Sugimoto M, Tokiwa M, Suzuki E, Kajihara S, Fujita Y, Iwamoto S, Tanaka K, Toi M.
  • Journal Title: Biochem Biophys Res Commun. Volume: 469(4) Issue: 4 Pages: 1140-1145
  • DOI: 10.1016/j.bbrc.2015.12.114
  • Peer Reviewed / Open Access
• [Journal Article] Features of occlusal state in female Japanese patients with migraine: A case-controlled study. (2016)
  • Author(s): Takeuchi M, Saruta J, Kato M, Sugimoto M, Kamata Y, Shimizu T, To M, Kawata T, Igarashi H, Tsukinoki K.
  • Journal Title: Cranio Volume: －
  • Peer Reviewed
• [Journal Article] Metabolomic profiling reveals novel biomarkers of alcohol intake and alcohol-induced liver injury in community-dwelling men. (2016)
  • Author(s): Harada S, Takebayashi T, Kurihara A, Akiyama M, Suzuki A, Hatakeyama Y, Sugiyama D, Kuwabara K, Takeuchi A, Okamura T, Nishiwaki Y, Tanaka T, Hirayama A, Sugimoto M, Soga T, Tomita M.
  • Journal Title: Environ Health Prev Med. Volume: 21(1) Issue: 1 Pages: 18-26
  • DOI: 10.1007/s12199-015-0494-y
  • NAID: 210000000441
  • Peer Reviewed / Open Access
• [Journal Article] Effects of processing and storage conditions on charged metabolomic profiles in blood. (2016)
  • Author(s): Hirayama A, Sugimoto M, Suzuki A, Hatakeyama Y, Enomoto A, Harada S, Soga T, Tomita M, Takebayashi T.
  • Journal Title: Electrophoresis. Volume: － Issue: 18 Pages: 2148-2155
  • DOI: 10.1002/elps.201400600
  • Peer Reviewed
• [Journal Article] H3K9MTase G9a is essential for the differentiation and growth of tenocytes in vitro (2015)
  • Author(s): Wada S, Ideno H, Shimada A, Kamiunten T, Nakamura Y, Nakashima K, Kimura H, Shinkai Y, Tachibana M, Nifuji A.
  • Journal Title: Histochem Cell Biol. Volume: in press Issue: 1 Pages: 13-20
  • DOI: 10.1007/s00418-015-1318-2
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Effects of 3-styrylchromones on metabolic profiles and cell death in oral squamous cell carcinoma cells (2015)
  • Author(s): Sakagami H., Shimada C., Kanda Y., Amano O., Sugimoto M., Ota S., Soga T., Tomita M., Sato A., Tanuma S., Takao K., Sugita Y.
  • Journal Title: Toxicology Reports Volume: 2 Pages: 1281-1290
  • DOI: 10.1016/j.toxrep.2015.09.009
  • NAID: 120005960915
  • Peer Reviewed / Open Access
• [Journal Article] Alteration of metabolomic profiles by titanium dioxide nanoparticles in human gingivitis model (2015)
  • Author(s): Garcia-Contreras1 R, Susigmoto M, Umemura N, Kaneko M, Hatakeyama Y, Soga T, Tomita M, Scougall-Vilchis RJ, Contreras-Bulnes R, Nakajima H and Sakagami H
  • Journal Title: Biomaterials Volume: 57 Pages: 3340-3340
  • DOI: 10.1016/j.biomaterials.2015.03.059
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Cystathionine is a novel substrate of cystine/glutamate transporter: implications for immune function (2015)
  • Author(s): Kobayashi, S., Sato, M., Kasakoshi, T., Tsutsui, T., Sugimoto, M., Osaki, M., Okada, F., Igarashi, K., Hiratake, J., Homma, T., Conrad, M., Fujii, J., Soga, T., Bannai, S., Sato, H.
  • Journal Title: J. Biol. Chem. Volume: 290 Issue: 14 Pages: 8778-8788
  • DOI: 10.1074/jbc.m114.625053
  • Peer Reviewed / Open Access
• [Journal Article] Organization and evolution of brain lipidome revealed by large-scale analysis of human, chimpanzee, macaque, and mouse tissues. (2015)
  • Author(s): Bozek K, Wei Y, Yan Z, Liu X, Xiong J, Sugimoto M, Tomita M, Pääbo S, Sherwood CC, Hof PR, Ely JJ, Li Y, Steinhauser D, Willmitzer L, Giavalisco P, Khaitovich P.
  • Journal Title: Neuron. Volume: 85(4) Issue: 4 Pages: 695-702
  • DOI: 10.1016/j.neuron.2015.01.003
  • Peer Reviewed / Open Access
• [Journal Article] Coordinated expression of H3K9 histone methyltransferases during tooth development in mice (2015)
  • Author(s): Kamiunten T, Ideno H, Shimada A, Nakamura Y, Kimura H, Nakashima K, Nifuji A.
  • Journal Title: Histochem Cell Biol. Volume: 143 Issue: 3 Pages: 259-266
  • DOI: 10.1007/s00418-014-1284-0
  • Peer Reviewed / Open Access
• [Journal Article] Search for conditions to detect epigenetic marks and nuclear proteins in immunostaining of the testis and cartilage (2014)
  • Author(s): Hisashi Ideno, Akemi Shimada, Taichi Kamiunten, Kazuhiko Imaizumi, Yoshiki Nakamura,et al
  • Journal Title: Journal of Histology Volume: (in press) Pages: 1-8
  • DOI: 10.1155/2014/658293
  • Peer Reviewed / Open Access
• [Journal Article] Disturbed biopterin and folate metabolism in the Qdpr-deficient mouse. (2014)
  • Author(s): Xu F, Sudo Y, Sanechika S, Yamashita J, Shimaguchi S, Honda S, Sumi-Ichinose C, Mori-Kojima M, Nakata R, Furuta T, Sakurai M, Sugimoto M, Soga T, Kondo K, Ichinose H.
  • Journal Title: FEBS Letters Volume: 588 Issue: 21 Pages: 3924-3931
  • DOI: 10.1016/j.febslet.2014.09.004
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Comparative metabolite profiling of foxglove aphids (Aulacorthum solani Kaltenbach) on leaves of resistant and susceptible soybean strains. (2014)
  • Author(s): Sato D, Sugimoto M, Akashi H, Tomita M, Soga T.
  • Journal Title: Mol Biosyst. Volume: 10 Issue: 4 Pages: 909-915
  • DOI: 10.1039/c3mb70595a
  • Peer Reviewed / Open Access
• [Journal Article] Efficient expansion of mouse primary tenocytes using a novel collagen gel culture method (2014)
  • Author(s): Akemi Shimada, Satoshi Wada, Kouji Inoue, Hisashi Ideno, Taichi Kamiunten, Koichiro Komatsu, Akira Kudo, Yoshiki Nakamura,et al
  • Journal Title: Histochem Cell Biol Volume: (in press) Issue: 2 Pages: 205-215
  • DOI: 10.1007/s00418-014-1191-4
  • Peer Reviewed / Open Access
• [Journal Article] Promotion of Bone Formation around Alendronate-immobilized Screw-Type Titanium Implants after Implantation into Rat Molar Tooth Sockets (2014)
  • Author(s): Raita, Y, Komatsu, K, Nifuji, A, Sato, M, Morito, M, Hayakawa, T
  • Journal Title: Journal of Hard Tissue Biology Volume: 23 Issue: 2 Pages: 177-186
  • DOI: 10.2485/jhtb.23.177
  • NAID: 130004480650
  • ISSN: 1341-7649, 1880-828X
  • Peer Reviewed / Open Access
• [Presentation] Histone methyltransferase G9a is essential for osteoblastic differentiation and proliferation in vitro, and skull bone formation in vivo (2015)
  • Author(s): Ideno H, Komatsu K, Shimada A, Kamiunten T, Arai Y, Nakashima K, Araki R, Nakamura Y, Abe M、Tachibana M、Kimura H、Nifuji A
  • Organizer: 2015 ASCB Annual Meeting
  • Place of Presentation: San Diego Convention Center(San Diego, CA, USA)
  • Year and Date: 2015-12-12
  • Int'l Joint Research
• [Presentation] Essential roles of H3K9MTase G9a during tooth development (2015)
  • Author(s): Kamiunten T, Shimada A, Ideno H, Nakamura Y, Kimura H, Tachibana M, Nakashima K, Nifuji A
  • Organizer: 2015 ASCB Annual Meeting
  • Place of Presentation: San Diego Convention Center(San Diego, CA, USA)
  • Year and Date: 2015-12-12
  • Int'l Joint Research
• [Presentation] Annexin A5 inhibits bony outgrowth at tendon/ligament insertion sites. (2015)
  • Author(s): Shimada A, Arai Y, Wada S, Ideno H, Kamiunten T, Nakashima K, Komatsu K, Yamashita T, Ezura Y, Amizuka N, Pöschl E, Brachvogel B, Nakamura Y, Nifuji A
  • Organizer: ASBMR 2015 annual meeting
  • Place of Presentation: Washington State Convention Center(Seattle, WA, USA)
  • Year and Date: 2015-10-09
  • Int'l Joint Research
• [Presentation] Histone 3 lysine 9 methyltransferase G9a is essential for the growth and differentiation of tenocytes. (2015)
  • Author(s): WADA S, H. Ideno H, Shimada A, Kamiunten T, Nakamura Y, Nakashima K, Kimura H, Tachibana M, Nifuji A.
  • Organizer: ASBMR 2015 annual meeting
  • Place of Presentation: Washington State Convention Center(Seattle, WA, USA)
  • Year and Date: 2015-10-09
  • Int'l Joint Research
• [Presentation] アネキシンA5欠損マウスは歯の咬耗と腱付着部における顎骨の肥大を呈する (2015)
  • Author(s): 島田明美, 小松浩一郎, 新井嘉則, 大貫芳樹, 中島和久, 山下照仁, 奥村敏, 二藤彰
  • Organizer: 第57回歯科基礎医学会学術大会
  • Place of Presentation: 朱鷺メッセ（新潟県新潟市）
  • Year and Date: 2015-09-12
• [Presentation] ヒストン3リジン9メチル化酵素G9aは正常な歯牙発生に必要である (2015)
  • Author(s): 上運天太一, 出野尚, 中村芳樹, 中島和久, 島田明美, 二藤彰
  • Organizer: 第57回歯科基礎医学会学術大会
  • Place of Presentation: 朱鷺メッセ（新潟県新潟市）
  • Year and Date: 2015-09-12
• [Presentation] Annexin a5による腱・靭帯付着部（enthesis）における骨形成の調 (2015)
  • Author(s): 島田明美、新井嘉則、和田悟史、出野尚、上運天太一、中島和久、小松浩一郎、山下照仁、江面陽一、網塚憲生、中村芳樹、二藤彰
  • Organizer: 第33回日本骨代謝学会学術集会
  • Place of Presentation: 京王プラザホテル（東京都新宿区）
  • Year and Date: 2015-07-23
• [Presentation] ヒストンメチル化酵素G9aは腱細胞の増殖および分化に必須である (2015)
  • Author(s): 和田悟史、出野 尚、島田明美、上運天太一、中村芳樹、中島和久、木村宏、立花誠、 二藤 彰
  • Organizer: 第33回日本骨代謝学会学術集会
  • Place of Presentation: 京王プラザホテル（東京都新宿区）
  • Year and Date: 2015-07-23
• [Presentation] ヒストンメチル化酵素G9a欠損マウスは骨形成阻害を示す (2015)
  • Author(s): 出野 尚, 小松浩一郎, 島田明美, 上運天太一、新井嘉則、中島和久、荒木良子, 中村芳樹, 安倍真澄、立花 誠、木村 宏、二藤 彰
  • Organizer: 第33回日本骨代謝学会学術集会
  • Place of Presentation: 京王プラザホテル（東京都新宿区）
  • Year and Date: 2015-07-23
• [Presentation] ヒストンメチル化酵素G9a遺伝子の歯胚間葉における欠損は歯の成長阻害を生ずる (2015)
  • Author(s): 上運天太一、出野尚、島田明美、中島和久、中村芳樹、木村宏、立花誠、二藤彰
  • Organizer: 第33回日本骨代謝学会学術集会
  • Place of Presentation: 京王プラザホテル（東京都新宿区）
  • Year and Date: 2015-07-23