Identification of the microbiome associated with oral cancer and epigenomic abnormalities that reflect risk

• Project/Area Number: 20K10110
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 57060:Surgical dentistry-related
• Research Institution: The University of Tokyo
• Principal Investigator: Abe Masanobu 東京大学, 医学部附属病院, 講師 (10392333)
• Co-Investigator(Kenkyū-buntansha): 小笠原 徹 東京大学, 保健・健康推進本部, 講師 (20359623) ; 安部 貴大 神奈川歯科大学, 大学院歯学研究科, 教授 (20383250)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Project Status: Completed (Fiscal Year 2022)
• Budget Amount: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000); Fiscal Year 2022: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2021: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2020: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
• Keywords: 口腔がん / エピジェネティクス

Outline of Research at the Start

口腔粘膜は食物や化学物質をはじめ多種多様な外的刺激に曝露されており、その影響により、ゲノム・エピゲノム異常が蓄積することで口腔がんの素地が形成される。本研究では、全身疾患との関与が注目されている口オーラルマイクロバイオーム着目し、口腔がんの素地の形成および病態に関与する口腔内細菌叢とそれに伴うエピゲノム異常を探索・同定を試みる。

Outline of Final Research Achievements

We attempted to explore and identify the microbiome involved in the formation of the oral cancer predisposition. The target patients were limited to non-smokers; of the 39 oral cancer patients, 12 were non-smokers. Methylation status of five genes was examined for epigenomic abnormalities using the MSP method. The results showed that methylation abnormalities were found in 30% to 58% of the cases. The presence of genomic abnormalities was also examined for mutations in 46 cancer-related genes using a next-generation sequencer. The most common p53 mutation was found in 6 cases, followed by PIK3CA in 4 cases. As for the analysis of oral bacterial flora, stable bacterial flora could not be obtained.

Academic Significance and Societal Importance of the Research Achievements

口腔がんと関係する特異的なオーラルマイクロバイオームと、それを反映したエピゲノム異常が同定されれば、口腔がんのリスク診断や予防に貢献すると考えられる。口腔がんは喫煙の影響を多大に受けると考えられるため、本研究における解析対象は非喫煙者とその手術検体に絞っって行った。非喫煙者に生じた口腔癌１２例のDNAメチル化異常を５つの遺伝子に関して解析した。その結果、喫煙歴がないにも関わらず、メチル化異常を高頻度に認め、特異的なプロファイルを示した。口腔内細菌叢の解析に関しては、安定した細菌叢が得られるまでには至らなかったが、今後の研究に繋がる有益な情報を得た。

Research Products

• [Journal Article] Burden and Trends of Inflammatory Bowel Disease in Five Asian Countries From 1990 To 2019: A Comparison with the United States and the United Kingdom. (2023)
  • Author(s): Gu WJ, Ning FL, Jin HR, Zhao ZM, Lyu J, Pei JP, Cao SY, Zeng YJ, Abe M, Nishiyama K, Zhang CD.
  • Journal Title: Dis Colon Rectum Volume: 66 Issue: 4 Pages: 567-578
  • DOI: 10.1097/dcr.0000000000002491
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] A Comparative Study of Periodontal Health Status between International and Domestic University Students in Japan. (2023)
  • Author(s): Abe M, Ohsato A, Fujihara Y, Hoshi K, Yanagimoto S.
  • Journal Title: Int J Environ Res Public Health Volume: 20 Issue: 5 Pages: 3866-3866
  • DOI: 10.3390/ijerph20053866
  • Peer Reviewed / Open Access
• [Journal Article] Systemic Disorders Closely Associated with Malocclusion in Late Adolescence: A Review and Perspective. (2022)
  • Author(s): Abe M, Mitani A, Yao A, Hoshi K, Yanagimoto S.
  • Journal Title: Int J Environ Res Public Health Volume: 19 Issue: 6 Pages: 3401-3401
  • DOI: 10.3390/ijerph19063401
  • Peer Reviewed / Open Access
• [Journal Article] The burden and trend of gastric cancer and its plausible risk factors in East Asia from 1990 to 2019 (2022)
  • Author(s): Ning FL, Lyu J, Pei JP, Gu WJ, Zhang NN, Cao SY, Zeng YJ, Abe M, Nishiyama K, Zhang CD.
  • Journal Title: Scientific Reports Volume: 12 Issue: 1 Pages: 5980-5980
  • DOI: 10.1038/s41598-022-10014-4
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] High flow nasal oxygen versus conventional oxygen therapy in gastrointestinal endoscopy with conscious sedation: A systematic review and meta-analysis with trial sequential analysis. (2022)
  • Author(s): Gu WJ, Wang HT, Huang J, Pei JP, Nishiyama K, Abe M, Zhao ZM, Zhang CD.
  • Journal Title: Digestive Endoscopy Volume: 34 Issue: 6 Pages: 1136-1146
  • DOI: 10.1111/den.14315
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Surgical strategies for Siewert type II esophagogastric junction carcinomas: A randomized controlled trial. (2022)
  • Author(s): Tao K, Dong J, He S, Abe M, Xu Y, Yang F, Zong L.
  • Journal Title: Frontiers in Oncology Volume: 12 Pages: 852594-852594
  • DOI: 10.3389/fonc.2022.852594
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Oral Health in Japan: State-of-the-Art and Perspectives. (2022)
  • Author(s): Abe M, Mitani A, Yao A, Zong L, Zhang CD, Hoshi K, Yanagimoto S.
  • Journal Title: Int J Environ Res Public Health Volume: 19 Issue: 14 Pages: 8232-8232
  • DOI: 10.3390/ijerph19148232
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Global, Regional, and National Burdens with Temporal Trends of Early-, Intermediate-, and Later-onset Gastric Cancer from 1990 to 2019 and Predictions up to 2035. (2022)
  • Author(s): Ning FL, Zhang NN, Zhao ZM, Du WY, Zeng YJ, Abe M, Pei JP, Zhang CD.
  • Journal Title: Cancers Volume: 14 Issue: 21 Pages: 5417-5417
  • DOI: 10.3390/cancers14215417
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] A Modified TNM Classification for Primary Operable Colorectal Cancer. (2021)
  • Author(s): Zhang C, Mei Z, Pei J, Abe M, Zeng X, Huang Q, Nishiyama K, Akimoto N, Haruki K, Nan H, Meyerhardt JA, Zhang R, Li X, Ogino S, Ugai T.
  • Journal Title: JNCI Cancer Spectrum Volume: 5 Issue: 1
  • DOI: 10.1093/jncics/pkaa093
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Risk factors for anastomotic leakage after gastrectomy for Siewert type II/III adenocarcinoma of the esophagogastric junction: a retrospective case-control study. (2021)
  • Author(s): Li Y, Shi Y, You J, Hu W, Xu Y, Wei H, Abe M, Cheng J, Zong L, Dong J.
  • Journal Title: Journal of Bio-X Research Volume: 4 Issue: 02 Pages: 71-76
  • DOI: 10.1097/jbr.0000000000000092
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Use of application of navigation system to odontogenic benign tumors with maxilla. Biomedical Research (2021)
  • Author(s): Koseki J, Abe T, Miyamoto Y, Kashiwagi M, Ishibashi M, Taniguchi A, Suenaga H, Abe H, Abe M, Hoshi K.
  • Journal Title: Biomedical Research Volume: 32 Pages: 37-41
  • Peer Reviewed
• [Journal Article] The Challenge of Early Prevention of Periodontal Diseases in Japan. (2021)
  • Author(s): Abe M, Mitani A, Zong L., Hoshi K, Yanagimoto S.
  • Journal Title: Journal of Advanced Oral Research Volume: online Issue: 1 Pages: 5-6
  • DOI: 10.1177/23202068211022586
  • Peer Reviewed
• [Journal Article] A case of squamous cell carcinoma in the corner of the mouth in a patient with Behcet's disease. (2021)
  • Author(s): Ono S, Abe T, Abe M, Kubota K, Hoshi K.
  • Journal Title: J Oral Maxillofac Surg Med Pathol Volume: 33 Issue: 6 Pages: 610-613
  • DOI: 10.1016/j.ajoms.2021.05.004
  • Peer Reviewed
• [Journal Article] Ultrasound delivery of Chinese rhubarb promotes early recovery of gastrointestinal function after gastrectomy: a prospective randomized controlled study. (2021)
  • Author(s): Jia H, Wang S, Shen L, You J, Yang F, Abe M, Xu Y, Zong L.
  • Journal Title: Journal of Bio-X Research Volume: 4 Pages: 130-135
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Screening and Validation of a Novel T Stage-Lymph Node Ratio Classification for Operable Colon Cancer. (2021)
  • Author(s): Pei J, Zhang R, Zhang N, Zeng Y, Sun Z, Ma S, Zhou J, Li X, Fan J, Zhu J, Abe M, Mei Z, Shi G, Zhang C.
  • Journal Title: Annals of Translational Medicine Volume: 9 Issue: 20 Pages: 1513-1513
  • DOI: 10.21037/atm-21-3170
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Prognostic value of modified Lauren classification in gastric cancer. (2021)
  • Author(s): Ning F, N Zhang N, Wang J, Jin Y, Quan H, Pei J, Zhao Y, Zeng X, Abe M, Zhang C.
  • Journal Title: World Journal of Gastrointestinal Oncology Volume: 13 Issue: 9 Pages: 1184-1195
  • DOI: 10.4251/wjgo.v13.i9.1184
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] A Secondary Jejunal Malignant Melanoma from Nasa Mucosal Melanoma: Case Report. (2021)
  • Author(s): Xu Y, Duan Z, Hu W, Zhu K, Cui P, Du Z, Abe M, Zong L.
  • Journal Title: SAGE Open Medical Case Reports Volume: 9 Pages: 1-4
  • DOI: 10.1177/2050313x211053708
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] High Frequency and Long Duration of Toothbrushing Can Potentially Reduce the Risk of Common Systemic Diseases in Late Adolescence. (2021)
  • Author(s): Abe M, Mitani A, Zong L, Zhang C, Hoshi K, Yanagimoto S.
  • Journal Title: Special Care in Dentistry Volume: online Issue: 3 Pages: 317-318
  • DOI: 10.1111/scd.12670
  • Peer Reviewed / Open Access
• [Journal Article] Novel operative technique of advancement urethral meatoplasty utilizing buccal mucosa for Vulvar Paget's disease with urethral invasion: two case reports. (2020)
  • Author(s): Hoshi K et al.
  • Journal Title: J Med Case Rep Volume: 15(1) Issue: 1 Pages: 136-136
  • DOI: 10.1186/s13256-021-02729-1
  • Peer Reviewed / Open Access
• [Journal Article] Close Association between Awareness of Teeth-Alignment Disorder and Systemic Disorders in Late Adolescence. (2020)
  • Author(s): Hoshi K et al.
  • Journal Title: Healthcare (Basel) Volume: 9(4) Issue: 4 Pages: 370-370
  • DOI: 10.3390/healthcare9040370
  • Peer Reviewed / Open Access
• [Journal Article] T1-2N1M0 triple-negative breast cancer patients from the SEER database showed potential benefit from post-mastectomy radiotherapy. (2020)
  • Author(s): Wang X, Xu Y, Guo S, Zhang J, Abe M, Tan H, Wang S, Chen P, Zong L.
  • Journal Title: Oncology Letters Volume: 19 Pages: 735-744
  • DOI: 10.3892/ol.2019.11139
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Targeting Antibiotic Resistance Genes Is a Better Approach to Block Acquisition of Antibiotic Resistance Than Blocking Conjugal Transfer by Recipient Cells: A Genome-Wide Screening in Escherichia coli. (2020)
  • Author(s): Moriguchi K, Iffah-Rasyiqah F, Abe M, Kiyokawa K, Yamamoto S, Suzuki K.
  • Journal Title: Front Microbiol Volume: 10 Pages: 2939-2939
  • DOI: 10.3389/fmicb.2019.02939
  • Peer Reviewed / Open Access
• [Journal Article] 頬粘膜部に発生した周辺性エナメル上皮腫の１例 A Case Report of Peripheral Ameloblastoma of Buccal Mucosa. (2020)
  • Author(s): 小松 紀子、柏木美樹、阿部 雅修、安部 貴大、星 和人
  • Journal Title: 日本口腔診断学会雑誌 Volume: 33 Pages: 34-38
  • Peer Reviewed
• [Journal Article] Harvest of at least eighteen lymph nodes is associated with improved survival in patients with pN0 colon cancer: A retrospective cohort study. (2020)
  • Author(s): Ning FL., Pei JP., Zhang NN., Wang J., Quan HG., Mei ZB., Zeng XT., Abe M., Zhang CD.
  • Journal Title: J Cancer Res Clin Oncol Volume: 146 Pages: 2117-2133
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] 軟口蓋に発生した血管周囲類上皮細胞腫瘍の1例 A case of Perivascular epithelioid cell tumor of the palatine mucosa. (2020)
  • Author(s): 小松 紀子、安部 貴大、白井 怜奈、谷口 明紗子、阿部 雅修、星 和人
  • Journal Title: 日本口腔外科学会雑誌 Volume: 66 Pages: 371-375
  • Peer Reviewed
• [Journal Article] Close Associations of Gum Bleeding with Systemic Diseases in Late Adolescence. (2020)
  • Author(s): Abe M, Mitani A, Yao A, Takeshima H, Zong L, Hoshi K, Yanagimoto S.
  • Journal Title: Int J Environ Res Public Health Volume: 17 Issue: 12 Pages: 4290-4290
  • DOI: 10.3390/ijerph17124290
  • Peer Reviewed / Open Access
• [Journal Article] Large Gender Gap of Oral Hygiene Behavior and Its Impact on Gingival Health in Late Adolescence. (2020)
  • Author(s): Abe M, Mitani A, Hoshi K, Yanagimoto S.
  • Journal Title: Int J Environ Res Public Health Volume: 17 Pages: 4394-4394
  • Peer Reviewed / Open Access
• [Journal Article] Awareness of Malocclusion Is Closely Associated with Allergic Rhinitis, Asthma, and Arrhythmia in Late Adolescents. (2020)
  • Author(s): Abe M, Mitani A, Yao A, Zong L, Hoshi K, Yanagimoto S.
  • Journal Title: Healthcare Volume: 8 Issue: 3 Pages: 209-209
  • DOI: 10.3390/healthcare8030209
  • Peer Reviewed
• [Journal Article] Huge Mesenteric Fibromatosis Presenting with Intestinal Perforation and Acute Diffuse Peritonitis: A Case Report. (2020)
  • Author(s): Xu Y, Duan Z, Hu W, Zhu K, You J, Abe M, Chen P, Zhang, Q, Zong L.
  • Journal Title: Translational Cancer Research Volume: 9 Issue: 9 Pages: 5674-5678
  • DOI: 10.21037/tcr-19-1151
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] TET repression and increased DNMT activity synergistically induce aberrant DNA methylation (2020)
  • Author(s): Takeshima Hideyuki、Niwa Tohru、Yamashita Satoshi、Takamura-Enya Takeji、Iida Naoko、Wakabayashi Mika、Nanjo Sohachi、Abe Masanobu、Sugiyama Toshiro、Kim Young-Joon、Ushijima Toshikazu
  • Journal Title: Journal of Clinical Investigation Volume: 130 Issue: 10 Pages: 5370-5379
  • DOI: 10.1172/jci124070
  • Peer Reviewed
• [Journal Article] The feasibility of laparoscopic TSME preserving the left colic artery and superior rectal artery for upper rectal cancer. (2020)
  • Author(s): Zhang C, Wei HT, Hu W, Sun Y, Zhang Q, Abe M, Du Z, Xu Y, Zong L, Hu X.
  • Journal Title: World J Surg Oncol Volume: 18 Issue: 1 Pages: 212-212
  • DOI: 10.1186/s12957-020-01986-6
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Prognostic values of preoperative inflammatory and nutritional markers for colorectal cancer. (2020)
  • Author(s): Zhang N, Ning, F, Guo R, Pei J, Qiao Y, Fan J, Jiang B, Liu Y, Chi Z, Mei Z, Abe M, Zhu J, Zhang R, Zhang C.
  • Journal Title: Front Oncol Volume: 10 Pages: 585083-585083
  • DOI: 10.3389/fonc.2020.585083
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Presentation] Promoter methylation occurs at high frequencies regardless of mutation status of tumor-associated genes in oral malignancies. (2023)
  • Author(s): Abe M, Ushijima T, Hoshi K.
  • Organizer: AACR Annual meeting 2023
  • Int'l Joint Research
• [Presentation] Methylation-silencing is frequently observed in oral malignancies regardless of mutations of tumor-related genes. (2022)
  • Author(s): Abe M, Ushijima T, Hoshi K.
  • Organizer: The 12th AACR-JCA Joint Conference on Breakthroughs in Cancer Research
  • Int'l Joint Research
• [Presentation] Gender Difference in Oral Hygiene Behavior and Its Impact on Periodontal Health. (2021)
  • Author(s): Abe M, Mitani A, Yao A, Ohsato A, Zong L, Yanagimoto S, Hoshi K.
  • Organizer: The 1st Annual Meeting of the International Society of Oral Care and The 18th Annual Meeting of the Japanese Society of Oral Care Joint Congress
  • Int'l Joint Research
• [Presentation] Associations of Gingivitis with Systemic Diseases in Late Adolescence in Japan. (2021)
  • Author(s): Abe M, Mitani A, Yao A, Ohsato A, Zong L, Yanagimoto S, Hoshi K.
  • Organizer: The 1st Annual Meeting of the International Society of Oral Care and The 18th Annual Meeting of the Japanese Society of Oral Care Joint Congress
  • Int'l Joint Research
• [Presentation] 青年期における歯肉出血と全身疾患との強固な関係性 (2021)
  • Author(s): 阿部雅修、三谷明久、八尾厚史、大里愛、星和人、柳元伸太郎
  • Organizer: 第18回日本口腔ケア学会総会・学術大会 第1回国際口腔ケア学会総会・学術大会 合同会議
• [Presentation] 青年期における口腔衛生意識の男女格差 (2021)
  • Author(s): 阿部雅修、三谷明久、八尾厚史、大里愛、星和人、柳元伸太郎
  • Organizer: 第18回日本口腔ケア学会総会・学術大会 第1回国際口腔ケア学会総会・学術大会 合同会議
• [Presentation] 不正咬合と密接に関係する全身疾患のスクリーニング (2021)
  • Author(s): 阿部雅修、星和人
  • Organizer: 第66回日本口腔外科学会総会・学術大会
• [Presentation] 青年期における歯肉炎と中・外耳炎および喘息の既往との密接な関係 (2020)
  • Author(s): 阿部雅修、三谷明久、柳元伸太郎、星和人
  • Organizer: 第17回日本口腔ケア学会総会・学術大会
• [Presentation] 青年期における口腔健康意識・行動の男女格差 (2020)
  • Author(s): 阿部雅修、藤原夕子、谷口明紗子、久保田恵吾、内野夏子、成田理香、小松紀子、大里愛、西條英人、星和人
  • Organizer: 第17回日本口腔ケア学会総会・学術大会
• [Presentation] 青年期の口腔衛生行動における性差と歯周病リスクの関係性 (2020)
  • Author(s): 阿部雅修、三谷明久、八尾厚史、星和人、柳元伸太郎
  • Organizer: 第58回全国大学保健管理研究集会