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Analysis of candidate factors for the treatment and biomarker of oral squamous cell carcinoma by data driven

Research Project

Project/Area Number 21K10079
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 57060:Surgical dentistry-related
Research InstitutionKyushu Dental College

Principal Investigator

Mabu HABU  九州歯科大学, 歯学部, 講師 (00360058)

Co-Investigator(Kenkyū-buntansha) 松原 琢磨  九州歯科大学, 歯学部, 准教授 (00423137)
矢田 直美  九州歯科大学, 歯学部, 准教授 (60468022)
柳沼 樹  九州歯科大学, 歯学部, 助教 (60845064)
Project Period (FY) 2021-04-01 – 2024-03-31
Project Status Completed (Fiscal Year 2023)
Budget Amount *help
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2023: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2022: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2021: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Keywords口腔扁平上皮癌 / 潜在的頸部リンパ節転移 / バイオマーカー / DKK1 / CKAP4 / 舌がん / リンパ節転移 / DKK-1 / 口腔扁平上皮がん / 口腔がん / 扁平上皮がん
Outline of Research at the Start

がんに関わる大規模データベース利用し,頭頸部扁平上皮がん患者499人のがん組織に発現する遺伝子量と生存率の相関を調べてきた.すると,Wntシグナルの阻害因子で分泌タンパク質のDKK-1の発現量が最も生存率と負の相関があることを明らかとなった.そこで本研究では,ヒト口腔扁平上皮がん細胞対してDKK-1を過剰発現またはノックアウトし,細胞の増殖・浸潤・移動能を調べる.さらに同細胞をヌードマウスに接種し,In vivoでDKK-1発現が口腔扁平上皮がんの増殖・浸潤・転移に与える影響を同定する.

Outline of Final Research Achievements

In order to investigate biomarkers predicting potential cervical lymph node metastasis in oral squamous cell carcinoma, we used TCGA to search for factors thought to be correlated with prognosis in head and neck cancer, and we found that DKK1 was involved. We focused on the expression of DKK1 and its receptor CKAP4 in 54 cases of tongue squamous cell carcinoma and investigated its relationship with cervical lymph node metastasis. As a result, patients with tongue squamous cell carcinoma who were positive for both DKK1 and CKAP4 were significantly more likely to have metastasis to the cervical lymph nodes. These results suggest that the simultaneous expression of DKK1 and CKAP4 may be an effective biomarker for predicting the possibility of potential cervical lymph node metastasis in tongue squamous cell carcinoma.

Academic Significance and Societal Importance of the Research Achievements

口腔癌において頸部リンパ節転移の有無は予後を左右する重要な因子である。しかし,明らかな頸部リンパ節転移がない症例に、積極的な予防的治療を行うかについては,意見が分かれている。今回の研究では,大規模データベース解析を利用することで,予後と関連があると思われるタンパク質を抽出し,口腔癌における頸部リンパ節転移症例とこのタンパク質との相関を調べることで,潜在的な頸部リンパ節転移の予測因子にできるのではないかと考えた。結果,DKK1とCKAP4というタンパク質が共に発現している症例では,高頻度に頸部リンパ節転移が認められたことから,頸部リンパ節転移に対する有効なバイオマーカーとなり得ると考えられた。

Report

(4 results)
  • 2023 Annual Research Report   Final Research Report ( PDF )
  • 2022 Research-status Report
  • 2021 Research-status Report
  • Research Products

    (16 results)

All 2024 2023 2022 2021

All Journal Article (7 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 7 results,  Open Access: 5 results) Presentation (9 results) (of which Invited: 4 results)

  • [Journal Article] Association between lymph node ratio and survival outcomes in patients with oral squamous cell carcinoma2024

    • Author(s)
      Haraguchi Kazuya、Habu Manabu、Takahashi Osamu、Tominaga Kazuhiro、Yoshioka Izumi、Sasaguri Masaaki
    • Journal Title

      Journal of Stomatology, Oral and Maxillofacial Surgery

      Volume: - Issue: 3 Pages: 101816-101816

    • DOI

      10.1016/j.jormas.2024.101816

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Enhanced degradation of epidermal growth factor receptor by metformin2023

    • Author(s)
      Yamagata Mayuka、Higashi Sen、Yaida Noboru、Ichihara Akane、Habu Manabu、Sasaguri Masaaki、Tominaga Kazuhiro、Takeuchi Hiroshi
    • Journal Title

      Oral Science International

      Volume: 1 Issue: 1 Pages: 1-9

    • DOI

      10.1002/osi2.1179

    • Related Report
      2022 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Human telomerase reverse transcriptase protein expression is associated with survival in patients with oral squamous cell carcinoma2022

    • Author(s)
      Kazuya Haraguchi, Manabu Habu et al
    • Journal Title

      Int J Clin Exp Pathol.

      Volume: 15 Pages: 29-37

    • Related Report
      2022 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Human telomerase reverse transcriptase protein expression is associated with survival in patients with oral squamous cell carcinoma2022

    • Author(s)
      Haraguchi K, Habu M, Yada N, Sasaguri M, Yoshioka I, Tominaga K
    • Journal Title

      Int J Clin Exp Pathol

      Volume: 15 Pages: 29-37

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Effective ancillary role and long-term course of daily or weekly teriparatide treatment on refractory medication-related osteonecrosis of the jaw (MRONJ): a clinical case series.2021

    • Author(s)
      Yoshiga D
    • Journal Title

      British Journal of Oral & Maxillofacial Surgery.

      Volume: 21 Issue: 5 Pages: 335-7

    • DOI

      10.1016/j.bjoms.2021.10.004

    • Related Report
      2021 Research-status Report
    • Peer Reviewed
  • [Journal Article] Substituent effects of cyclic naphthalene diimide on G-quadruplex binding and the inhibition of cancer cell growth.2021

    • Author(s)
      Fukuda, H., Sato, S., Zou, T., Higashi, S., Takahashi, O., Habu, M., Sasaguri, M., Tominaga, K., Takenaka, S., Takeuchi, H.
    • Journal Title

      Bioorg. Med. Chem. Lett.

      Volume: 50 Pages: 128323-128323

    • DOI

      10.1016/j.bmcl.2021.128323

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] epth of invasion determined by magnetic resonance imaging in tongue cancer can be a predictor of cervical lymph node metastasis.2021

    • Author(s)
      Haraguchi K, Yoshiga D, Oda M, Tabe S, Mitsugi S, Takahashi O, Habu M, Sasaguri M, Morimoto Y, Yoshioka I, Tominaga K
    • Journal Title

      Oral Surg Oral Med Oral Pathol Oral Radiol

      Volume: 131 Issue: 2 Pages: 231-240

    • DOI

      10.1016/j.oooo.2020.07.005

    • Related Report
      2021 Research-status Report
    • Peer Reviewed
  • [Presentation] The combination and order of low JCHAIN, high PGK1, low MAEA, and high ST13 expression are related with poor prognosis for head and neck squamous cell carcinoma.2024

    • Author(s)
      1.Habu M, Fujita H, Haraguchi K, Takahashi O, Yoshiga D, Sasaguri M, Kokabu S , Yoshioka I
    • Organizer
      第42回日本口腔腫瘍学会
    • Related Report
      2023 Annual Research Report
  • [Presentation] AIを用いた口腔粘膜疾患診断支援システムによる初期舌癌の識別能力.2023

    • Author(s)
      2.土生 学、大谷 泰志、吉岡 泉、笹栗正明
    • Organizer
      第68回日本口腔外科学会
    • Related Report
      2023 Annual Research Report
  • [Presentation] 顎顔面補綴の観点から考える顎骨再建 シンポジウム2022

    • Author(s)
      土生 学
    • Organizer
      第39回日本顎顔面補綴学会総会
    • Related Report
      2022 Research-status Report
    • Invited
  • [Presentation] みんなで学ぶ顎関節症の鑑別疾患 シンポジウム2022

    • Author(s)
      土生 学
    • Organizer
      第35回日本顎関節学会総会
    • Related Report
      2022 Research-status Report
    • Invited
  • [Presentation] 骨格性Ⅱ級症例に対する上顎単独骨切り術の適応と術式の要点 シンポジウム2022

    • Author(s)
      土生 学
    • Organizer
      第32回日本顎変形症学会総会
    • Related Report
      2022 Research-status Report
    • Invited
  • [Presentation] 予防的頸部郭清術の適応を再考する2022

    • Author(s)
      藤田浩範、土生 学
    • Organizer
      日本口腔腫瘍学会
    • Related Report
      2022 Research-status Report
  • [Presentation] 予防的頸部郭清術の適応と注意すべきポイント2021

    • Author(s)
      土生 学
    • Organizer
      日本口腔外科学会
    • Related Report
      2021 Research-status Report
    • Invited
  • [Presentation] 放射線性骨髄炎による病的下顎骨骨折に対して遊離肩甲骨皮弁による硬性再建を行った一例2021

    • Author(s)
      土生 学
    • Organizer
      日本口腔顎顔面外傷学会
    • Related Report
      2021 Research-status Report
  • [Presentation] 予防的頸部郭清術の適応を再考する2021

    • Author(s)
      藤田浩範、土生 学
    • Organizer
      日本口腔腫瘍学会
    • Related Report
      2021 Research-status Report

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Published: 2021-04-28   Modified: 2025-01-30  

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