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Treatment strategies for oral squamous cell carcinoma based on genetic alterlations

Research Project

Project/Area Number 20H03890
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Review Section Basic Section 57060:Surgical dentistry-related
Research InstitutionEhime University

Principal Investigator

Nakashiro Koichi  愛媛大学, 医学系研究科, 准教授 (90314880)

Co-Investigator(Kenkyū-buntansha) 合田 啓之  愛媛大学, 医学部附属病院, 講師 (00464371)
徳善 紀彦  愛媛大学, 医学部附属病院, 助教 (10723843)
内田 大亮  愛媛大学, 医学系研究科, 教授 (20335798)
Project Period (FY) 2020-04-01 – 2023-03-31
Project Status Completed (Fiscal Year 2022)
Budget Amount *help
¥18,070,000 (Direct Cost: ¥13,900,000、Indirect Cost: ¥4,170,000)
Fiscal Year 2022: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2021: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2020: ¥9,490,000 (Direct Cost: ¥7,300,000、Indirect Cost: ¥2,190,000)
Keywords口腔扁平上皮癌 / 遺伝子異常 / 頸部リンパ節転移予測 / リッキドバイオプシー / ゲノム異常 / エピゲノム異常 / 転移予測 / リンパ節転移予測 / 核酸創薬 / リキッドバイオプシー / 再発監視
Outline of Research at the Start

がんは、遺伝子異常により生じることが広く知られている。口腔がんも例外ではなく、遺伝子の異常が多数報告されている。しかしながら、このような知見は実際の日常診療では全く活用されていないのが現状である。そこで、本研究ではこれまでにわれわれが明らかにしてきた遺伝子異常に基づいた口腔がんに対する新規治療戦略を確立することを目的とする。すなわち、頸部リンパ節転移予測、再発監視、再発・転移難治性がんに対する新規治療法に遺伝子異常所見を活用することにより、口腔がんの完全制御を目指す。

Outline of Final Research Achievements

It is widely known that human malignancies are caused by genomic and epigenomic alterations. Therefore, we have attempted to identify gene alterations that would be useful in the diagnosis and treatment of oral squamous cell carcinoma. We extracted genomic DNA and total RNA from the primary tumor and adjacent normal tissues, and performed gene mutation analysis using targeted deep sequencing and comprehensive gene expression analysis by microarray. In the mutation analysis, mutations in TP53 gene were observed in 90% of the cases. On the other hand, the expression analysis revealed numerous genes that showed significant correlations with cervical lymph node metastasis and distant metastasis. These gene alterations have the potential to be useful for predicting metastasis and monitoring recurrence for oral squamous cell carcinoma.

Academic Significance and Societal Importance of the Research Achievements

わが国では超高齢社会の到来とともに口腔扁平上皮癌の罹患数は増加しており、2019 年の時点で年間約 11,000 人とされ、5 年生存率は約 60% にとどまっている。本研究成果により、口腔癌診療に遺伝子異常所見が用いられるようになれば、潜在性頸部リンパ節転移や微小残存病変の把握、さらに有効な分子標的薬の選択が可能となり、適切な治療法による治療成績の飛躍的な向上が期待できる。また、無益な治療の回避により患者の治療後の生活の質が担保できる。

Report

(4 results)
  • 2022 Annual Research Report   Final Research Report ( PDF )
  • 2021 Annual Research Report
  • 2020 Annual Research Report
  • Research Products

    (25 results)

All 2022 2021 2020 2019

All Journal Article (8 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 8 results,  Open Access: 7 results) Presentation (17 results) (of which Invited: 1 results)

  • [Journal Article] The mutational spectrum in whole exon of p53 in oral squamous cell carcinoma and its clinical implications2022

    • Author(s)
      Hyodo Toshiki、Kuribayashi Nobuyuki、Fukumoto Chonji、Komiyama Yuske、Shiraishi Ryo、Kamimura Ryouta、Sawatani Yuta、Yaguchi Erika、Hasegawa Tomonori、Izumi Sayaka、Wakui Takahiro、Nakashiro Koh-ichi、Uchida Daisuke、Kawamata Hitoshi
    • Journal Title

      Scientific Reports

      Volume: 12 Issue: 1 Pages: 21695-21695

    • DOI

      10.1038/s41598-022-25744-8

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Molecular and histopathological analysis of peripheral ameloblastoma of the mandible mimicking a papillomatous lesion on the buccal mucosa2022

    • Author(s)
      Izumi S, Komiyama Y, Shimura M, Sawatani Y, Oshima R, Zama M, Fukumoto C, Kamimura R, Yaguchi E, Wakui T, Nakashiro K, Uchida D, Kawamata H
    • Journal Title

      J Oral Maxillofac Surg Med Pathol

      Volume: 34 Pages: 359-363

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Human papillomavirus?16 infection and p16 expression in oral squamous cell carcinoma2021

    • Author(s)
      Tokuzen Norihiko、Nakashiro Koh-ichi、Tojo Shin、Goda Hiroyuki、Kuribayashi Nobuyuki、Uchida Daisuke
    • Journal Title

      Oncology Letters

      Volume: 22 Issue: 1 Pages: 528-528

    • DOI

      10.3892/ol.2021.12789

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Oral squamous cell carcinoma may originate from bone marrow-derived stem cells2021

    • Author(s)
      Hasegawa T, Nakashiro KI, Fukumoto C, Hyodo T, Sawatani Y, Shimura M, Kamimura R, Kuribayashi N, Fujita A, Uchida D, Kawamata H.
    • Journal Title

      Oncol Lett

      Volume: 21 Issue: 2 Pages: 170-170

    • DOI

      10.3892/ol.2021.12431

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] MicroRNA-361-3p is a potent therapeutic target for oral squamous cell carcinoma.2020

    • Author(s)
      Ogawa H, Nakashiro KI, Tokuzen N, Kuribayashi N, Goda H, Uchida D.
    • Journal Title

      Cancer Sci.

      Volume: - Issue: 5 Pages: 1645-1651

    • DOI

      10.1111/cas.14359

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Whole Exome Sequencing of SMO, BRAF, PTCH1 and GNAS in Odontogenic Diseases.2020

    • Author(s)
      Shimura M, Nakashiro KI, Sawatani Y, Hasegawa T, Kamimura R, Izumi S, Komiyama Y, Fukumoto C, Yagisawa S, Yaguchi E, Hitomi-Koide M, Hyodo T, Uchida D, Kawamata H.
    • Journal Title

      In Vivo

      Volume: 34 Issue: 6 Pages: 3233-3240

    • DOI

      10.21873/invivo.12159

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Paclitaxel Potentiates the Anticancer Effect of Cetuximab by Enhancing Antibody-Dependent Cellular Cytotoxicity on Oral Squamous Cell Carcinoma Cells In Vitro.2020

    • Author(s)
      Sawatani Y, Komiyama Y, Nakashiro KI, Uchida D, Fukumoto C, Shimura M, Hasegawa T, Kamimura R, Hitomi-Koide M, Hyodo T, Kawamata H.
    • Journal Title

      Int J Mol Sci.

      Volume: 21 Issue: 17 Pages: 6292-6292

    • DOI

      10.3390/ijms21176292

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Valve Interstitial Cell-Specific Cyclooxygenase-1 Associated With Calcification of Aortic Valves.2019

    • Author(s)
      Sakaue T, Hamaguchi M, Aono J, Nakashiro KI, Shikata F, Kawakami N, Oshima Y, Kurata M,?Nanba D, Masumoto J, Yamaguchi O, Higashiyama S, Izutani H.
    • Journal Title

      Ann Thorac Surg

      Volume: S0003-4975 Issue: 1 Pages: 31717-5

    • DOI

      10.1016/j.athoracsur.2019.09.085

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Presentation] 口腔扁平上皮癌における microRNA-375 の機能と臨床応用2022

    • Author(s)
      雑賀将斗、中城公一、徳善紀彦、内田大亮
    • Organizer
      第46回日本頭頸部癌学会学術集会
    • Related Report
      2022 Annual Research Report
  • [Presentation] 口腔扁平上皮癌治療標的としての miR-346 の有用性2022

    • Author(s)
      白井博之、中城公一、徳善紀彦、雑賀将斗、内田大亮
    • Organizer
      第26回日本がん分子標的治療学会学術集会
    • Related Report
      2022 Annual Research Report
  • [Presentation] Clinical significance of CXCL13 as a novel biomarker in advance oral squamous cell carcinoma2022

    • Author(s)
      Tojo S, Kuribayashi N, Nakashiro K, Tokuzen N, Goda H, Kojima S, Uchida D
    • Organizer
      The 81th Annual Meeting of the Japanese Cancer Association
    • Related Report
      2022 Annual Research Report
  • [Presentation] Expression and function of microRNA-375 in human oral squamous cell carcinoma2022

    • Author(s)
      Saika M, Nakashiro K, Tokuzen N, Shirai H, Uchida D
    • Organizer
      The 81th Annual Meeting of the Japanese Cancer Association
    • Related Report
      2022 Annual Research Report
  • [Presentation] 口腔扁平上皮癌転移リンパ節の網羅的遺伝子発現解析2022

    • Author(s)
      徳善紀彦、中城公一、栗林伸行、合田啓之、内田大亮
    • Organizer
      第67回日本口腔外科学会総会・学術大会
    • Related Report
      2022 Annual Research Report
  • [Presentation] 口腔扁平上皮癌の遺伝子異常とその臨床的意義2022

    • Author(s)
      中城公一、徳善紀彦、栗林伸行、合田啓之、内田大亮
    • Organizer
      第67回日本口腔外科学会総会・学術大会
    • Related Report
      2022 Annual Research Report
    • Invited
  • [Presentation] ヒト口腔扁平上皮癌における頸部リンパ節転移予測マーカーの探索2022

    • Author(s)
      雑賀将斗、中城公一、徳善紀彦、栗林伸行、白井博之、内田大亮
    • Organizer
      第58回日本口腔組織培養学会学術大会・総会
    • Related Report
      2022 Annual Research Report
  • [Presentation] 唾液腺癌遠隔転移症例に対するがんゲノム医療の試み2021

    • Author(s)
      徳善紀彦,中城公一,合田啓之,内田大亮
    • Organizer
      第25回日本がん分子標的治療学会
    • Related Report
      2021 Annual Research Report
  • [Presentation] 口腔扁平上皮癌頸部リンパ節転移予測におけるmicroRNA-375の有用性2021

    • Author(s)
      雑賀将斗,中城公一,徳善紀彦,村上静郁,森野 恵,栗林伸行,合田啓之,内田大亮
    • Organizer
      第45回日本頭頸部癌学会
    • Related Report
      2021 Annual Research Report
  • [Presentation] 口腔扁平上皮癌における p53 遺伝子の変異解析2021

    • Author(s)
      児島さやか, 栗林 伸行, 中城 公一, 東條 晋, 徳善 紀彦, 合田 啓之, 川又 均, 内田 大亮
    • Organizer
      第34回日本口腔診断学会・第31回日本口腔内科学会合同学術大会
    • Related Report
      2021 Annual Research Report
  • [Presentation] High frequency of p53 gene mutations in oral squamous cell carcinoma2021

    • Author(s)
      Shin Tojo, Nobuyuki Kuribayashi, Koh-ichi Nakashiro, Norihiko Tokuzen, Hiroyuki Goda, Sayaka Kojima, Hitoshi Kawamata, Daisuke Uchida
    • Organizer
      第80回日本癌学会学術総会
    • Related Report
      2021 Annual Research Report
  • [Presentation] Downregulation of microRNA-375 is associated with lymph node metastasis in oral squamous cell carcinoma2021

    • Author(s)
      Masato Saika, Koh-ichi Nakashiro, Norihiko Tokuzen, Nobuyuki Kuribayashi, Hiroyuki Goda, Daisuke Uchida
    • Organizer
      第80回日本癌学会学術総会
    • Related Report
      2021 Annual Research Report
  • [Presentation] 口腔扁平上皮癌における新規腫瘍マーカーである CXCL13 の発現2021

    • Author(s)
      東條 晋,栗林伸行,中城公一,徳善紀彦,内田大亮
    • Organizer
      第57回日本口腔組織培養学会学術集会
    • Related Report
      2021 Annual Research Report
  • [Presentation] 高悪性度口腔扁平上皮癌の遺伝子変異と治療標的の探索2021

    • Author(s)
      徳善紀彦,中城公一,栗林伸行,合田啓之,内田大亮
    • Organizer
      第66回日本口腔外科学会総会・学術大会
    • Related Report
      2021 Annual Research Report
  • [Presentation] Whole-exome sequencing of p53 gene in oral squamous cell carcinoma2020

    • Author(s)
      Nobuyuki Kuribayashi, Koh-ichi Nakashiro, Norihiko Tokuzen, Hiroyuki Goda, Hitoshi Kawamata, Daisuke Uchida
    • Organizer
      第 79 回日本癌学会学術総会
    • Related Report
      2020 Annual Research Report
  • [Presentation] カスタム NGS パネルを用いた口腔扁平上皮癌ゲノム異常の検出2020

    • Author(s)
      中城公一、栗林伸行、東條 晋、徳善紀彦、合田啓之、内田大亮
    • Organizer
      第 44 回日本頭頸部癌学会
    • Related Report
      2020 Annual Research Report
  • [Presentation] 口腔悪性末梢神経鞘腫瘍における新規融合遺伝子の同定2020

    • Author(s)
      徳善紀彦、中城公一、合田啓之、栗林伸行、内田大亮
    • Organizer
      第 24 回日本がん分子標的治療学会
    • Related Report
      2020 Annual Research Report

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Published: 2020-04-28   Modified: 2024-01-30  

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