Devlopment of novel oral cancer treatment with non-coding RNA by targetting metastatic organ and cancer stem cells.

• Project/Area Number: 15H05045
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Surgical dentistry
• Research Institution: Kagoshima University
• Principal Investigator: Sugiura Tsuyoshi 鹿児島大学, 医歯学域歯学系, 教授 (40322292)
• Co-Investigator(Kenkyū-buntansha): 浜田 倫史 鹿児島大学, 医歯学域附属病院, 講師 (00444894) ; 熊丸 渉 九州大学, 大学病院, 講師 (90432947)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2018)
• Budget Amount: ¥17,550,000 (Direct Cost: ¥13,500,000、Indirect Cost: ¥4,050,000); Fiscal Year 2017: ¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000); Fiscal Year 2016: ¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000); Fiscal Year 2015: ¥10,140,000 (Direct Cost: ¥7,800,000、Indirect Cost: ¥2,340,000)
• Keywords: 口腔癌 / microRNA / 血清マーカー / 癌幹細胞 / 上皮間葉移行 / BRACHYURY / SOX2 / 癌 / マイクロRNA / Brachyury / 機能性RNA / 腫瘍マーカー / 口腔癌幹細胞

Outline of Final Research Achievements

Cancer cells produce short non-coding RNA and release to the body fluid. We discovered oral cancer specific microRNAs by comparing serum from normal and oral cancer indibiduals. These oral cancer specific microRNAs are the candidates for oral cancer biomarkers and we next analyzed quantitatively these microRNAs for each 40 normal and oral cancer serum samples. The oral cancer specific microRNA could diagnose oral cancer (sensitivity 67.5%) and normal individual (specificity 87.5%). This fact suggests the microRNA could be the serum marker for oral cancer.

Academic Significance and Societal Importance of the Research Achievements

本研究結果より血清microRNAにより口腔癌が診断できることが明らかとなった。口腔癌には腫瘍マーカーがなく、がん検診のような多数の住民を対象とした場合の第一段検査が無かったが、血液検査陽性個人にのみ第2段の精密検査を行うことを可能とする技術となる。さらに、口腔癌を治療した後の再発や転移についても血液検査により検出が可能である。口腔癌特異的microRNAは遺伝子発現を阻害する機能を持つため、将来的に治療に応用することも可能と考えられる。

Research Products

• [Journal Article] Transfection of T-Box Transcription Factor BRACHYURY and SOX2 Synergistically Promote Self-Renewal and Invasive Phenotype in Oral Cancer Cells (2018)
  • Author(s): Akimoto Naonari、Nakamura Kodai、Hijioka Hiroshi、Kume Kenichi、Matsumura Yoshiaki、Sugiura Tsuyoshi
  • Journal Title: International Journal of Molecular Sciences Volume: 19 Issue: 11 Pages: 3620-3620
  • DOI: 10.3390/ijms19113620
  • Peer Reviewed / Open Access
• [Journal Article] Deregulation of Nicotinamide N-Methyltransferase and Gap Junction Protein Alpha-1 Causes Metastasis in Adenoid Cystic Carcinoma (2018)
  • Author(s): Ishibashi, K., Ishii, K., Sugiura, T., Mori, Y.
  • Journal Title: Anticancer Research Volume: 38 Issue: 1 Pages: 187-197
  • DOI: 10.21873/anticanres.12207
  • Peer Reviewed / Open Access
• [Journal Article] Involvement of the T-box transcription factor Brachyury in early-stage embryonic mouse salivary gland. (2016)
  • Author(s): Hayashi K, Ikari T, Sugiyama G, Sugiura T, Ohyama Y,Kumamaru W, Shirasuna K,Mori Y.
  • Journal Title: Biochem Biophys Res Commun Volume: 477 Issue: 4 Pages: 814-819
  • DOI: 10.1016/j.bbrc.2016.06.140
  • Peer Reviewed / Open Access
• [Journal Article] Efficient regulation of branching morphogenesis via fibroblast growth factor receptor 2c in early-stage embryonic mouse salivary glands. (2016)
  • Author(s): Shibuya M., Ikari T., Sugiyama G., Ohyama Y., Kumamaru W., Nagano K., Sugiura T., Shirasuna K. and Mori Y.
  • Journal Title: Differentiation Volume: 92(4) Issue: 4 Pages: 216-224
  • DOI: 10.1016/j.diff.2016.05.005
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Expression levels of SOX2, KLF4 and brachyury transcription factors are associated with metastasis and poor prognosis in oral squamous cell carcinoma (2016)
  • Author(s): Yoshihama R, Yamaguchi K, Imajyo I, Mine M, Hiyake N, Akimoto N, Kobayashi Y, Chigita S, Kumamaru W, Kiyoshima T, Mori Y, Sugiura T
  • Journal Title: Oncology letters Volume: 11 Issue: 2 Pages: 1435-1446
  • DOI: 10.3892/ol.2015.4047
  • Peer Reviewed / Open Access
• [Journal Article] Aberrant methylation of MUC1 and MUC4 promoters are potential prognostic biomarkers for pancreatic ductal adenocarcinomas (2016)
  • Author(s): Yokoyama, S. Higashi, M. Kitamoto, S. Oeldorf, M. Knippschild, U. Kornmann, M. Maemura, K. Kurahara, H. Wiest, E. Hamada, T. Kitazono, I. Goto, Y. Tasaki, T. Hiraki, T. Hatanaka, K. Mataki, Y. Taguchi, H. Hashimoto, S. Batra, S. K. Tanimoto, A. Yonezawa, S. Hollingsworth, M. A.
  • Journal Title: Oncotarget Volume: - Issue: 27 Pages: 42553-42565
  • DOI: 10.18632/oncotarget.9924
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] A Novel Function of CD82/KAI1 in Sialyl Lewis Antigen-Mediated Adhesion of Cancer Cells: Evidence for an Anti-Metastasis Effect by Down-Regulation of Sialyl Lewis Antigens. (2015)
  • Author(s): Yoshihama N, Yamaguchi K, Chigita S, Mine M, Abe M, Ishii K, Kobayashi Y, Akimoto N, Mori Y, Sugiura T
  • Journal Title: PLoS One Volume: 10 Issue: 4 Pages: e0124743-e0124743
  • DOI: 10.1371/journal.pone.0124743
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] miR-203 Inhibits Frizzled-2 Expression via CD82/KAI1 Expression in Human Lung Carcinoma Cells. (2015)
  • Author(s): Mine M, Yamaguchi K, Sugiura T, Chigita S, Yoshihama N, Yoshihama R, Hiyake N, Kobayashi Y, Mori Y:
  • Journal Title: PLoS One Volume: 10 Issue: 7 Pages: e0131350-e0131350
  • DOI: 10.1371/journal.pone.0131350
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Presentation] Detecting oral squamous cell carcinoma by novel serum microRNA panel (2018)
  • Author(s): 中村康大、杉浦剛
  • Organizer: 第77 回日本癌学会学術総会
• [Presentation] 新規血清microRNA による口腔扁平上皮癌の検出 (2018)
  • Author(s): 中村康大、杉浦剛
  • Organizer: 第63 回公益社団法人口腔外科学会総会・学術総会
• [Presentation] DNA methylation of tumor relatedgenes in gargled fluid: A noninvasive method for detecting oral precancerous lesion (2018)
  • Author(s): 浜田倫史、杉浦剛
  • Organizer: 第77 回日本癌学会学術総会
• [Presentation] 非侵襲的口腔検体検査のススメ 口腔がんから全身疾患まで、その有用性と展望 (2017)
  • Author(s): 杉浦 剛
  • Organizer: 第28 回近畿 中国 四国 口腔衛生学会総会
  • Invited
• [Presentation] Novel serum microRNAs specific for oral squamous cell carcinoma: its usefulness for early detection (2017)
  • Author(s): 中村康大、杉浦剛
  • Organizer: 第76回 日本癌学会学術総会
• [Presentation] 口腔扁平上皮癌における血清microRNAの検出とその診断的意義 (2016)
  • Author(s): 中村康大、日焼菜央美、浜田倫史、杉浦剛
  • Organizer: 第３４回日本口腔腫瘍学会総会・学術大会
  • Place of Presentation: 横浜開港記念会館（神奈川県横浜市）
  • Year and Date: 2016-01-21
• [Presentation] 口腔扁平上皮癌におけるMUC1/MUC4 ムチン共発現の予後規定因子としての有用性の検討 (2016)
  • Author(s): 浜田倫史, 上村祐二, 中村康大, 上川善昭, 杉浦剛
  • Organizer: 第70回NPO法人日本口腔科学会学術集会
• [Presentation] 口腔癌早期発見に向けた当科の取り組み (2016)
  • Author(s): 浜田倫史、中村康大、大河原綾子、比地岡浩志、石田喬之、久米健一、中村典史、杉浦剛
  • Organizer: 九州地区口腔癌研究会 第20回学術講演会
• [Presentation] 口腔扁平上皮癌における血清microRNAの検出とその診断的意義 (2016)
  • Author(s): 中村康大、浜田倫史、杉浦剛
  • Organizer: 第34回日本口腔腫瘍学会総会・学術大会
• [Presentation] 口腔扁平上皮癌診断マーカーとしての血清microRNAの探索 (2016)
  • Author(s): 中村康大、浜田倫史、杉浦剛
  • Organizer: 第70回NPO法人日本口腔科学会学術集会
• [Presentation] Combination of serum microRNAs for biomarker in oral squamous cell carcinoma (2016)
  • Author(s): Koudai Nakamura , Naomi Hiyake , Tomofumi Hamada , Tsuyoshi Sugiura
  • Organizer: 第75回日本癌学会学術総会
• [Presentation] 口腔扁平上皮癌の検出に有用な血清microRNAの検討 (2016)
  • Author(s): 中村康大、日焼菜央美、松村吉晃、後藤雄一、浜田倫史、杉浦剛
  • Organizer: 第61回日本口腔外科学会総会・学術大会
• [Presentation] Identification of serum microRNAs as biomarker for oral squamous cell carcinoma (2015)
  • Author(s): 日焼菜央美、杉浦剛、吉濱直哉、秋本直柔、峯真理子、吉濱るみ、森悦秀
  • Organizer: 第７４回日本癌学会学術総会
  • Place of Presentation: 名古屋国際会議場(愛知県名古屋市）
  • Year and Date: 2015-10-08
• [Presentation] Downregulation of delta-Np63 induces a mesenchymal cell phenotype, possibly involoving invasion and metastasis of OSCC (2015)
  • Author(s): 後藤雄一、河野新太郎、松原良太、橋口有真、坂元泰基、金子直樹、丸瀬靖之、神野哲平、中村康大、浜田倫史、大部一成、杉浦剛、中村誠司
  • Organizer: 第７４回日本癌学会学術総会
  • Place of Presentation: 名古屋国際会議場（愛知県名古屋市）
  • Year and Date: 2015-10-08
• [Presentation] MUC$ expression is correlated to cisplatin chemoresistance in oral squamouse cell carcinoma (2015)
  • Author(s): 浜田倫史、中村康大、後藤雄一、杉浦剛
  • Organizer: 第７４回日本癌学会学術総会
  • Place of Presentation: 名古屋国際会議場（愛知県名古屋市）
  • Year and Date: 2015-10-08
• [Presentation] 口腔扁平上皮癌患者における血清腫瘍マーカーmicroRNAの探索 (2015)
  • Author(s): 日焼菜央美、杉浦剛、峯真理子、吉濱るみ、秋本直柔、吉濱直哉、千北さとみ、小林洋輔、熊丸渉、森悦秀
  • Organizer: 第６９回日本口腔科学会学術集会
  • Place of Presentation: 大阪国際会議場(大阪府大阪市）
  • Year and Date: 2015-05-13
• [Presentation] 含嗽液を用いた癌抑制遺伝子DNAメチル化異常の検出 (2015)
  • Author(s): 浜田倫史、熊谷直之、後藤雄一、上川善昭、杉浦剛
  • Organizer: 第６９回日本口腔科学会学術集会
  • Place of Presentation: 大阪国際会議場（大阪府大阪市）
  • Year and Date: 2015-05-13
• [Patent(Industrial Property Rights)] 口腔癌判定装置、口腔癌判定方法、プログラム及び口腔癌判定キット (2018)
  • Inventor(s): 中村康大、杉浦剛、浜田倫史
  • Industrial Property Rights Holder: 中村康大、杉浦剛、浜田倫史
  • Industrial Property Rights Type: 特許
  • Filing Date: 2018
• [Patent(Industrial Property Rights)] METHOD FOR DETECTING PRECANCEROUS ORAL LESION (2017)
  • Inventor(s): HAMADA Tomofumi
  • Industrial Property Rights Holder: HAMADA Tomofumi
  • Industrial Property Rights Type: 特許
  • Filing Date: 2017
  • Overseas
• [Patent(Industrial Property Rights)] 口腔前癌病変の検出方法 (2017)
  • Inventor(s): 浜田倫史
  • Industrial Property Rights Holder: 浜田倫史
  • Industrial Property Rights Type: 特許
  • Patent Publication Number: 2017-046628
  • Filing Date: 2017
  • Acquisition Date: 2017