Establishment of screening methods for oral cancer/oral dysplasia with multi-omics based methods

• Project/Area Number: 17K11897
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Surgical dentistry
• Research Institution: Yamagata University
• Principal Investigator: Ishikawa Shigeo 山形大学, 医学部, 助教 (00466640)
• Co-Investigator(Kenkyū-buntansha): 杉本 昌弘 慶應義塾大学, 政策・メディア研究科(藤沢), 特任教授 (30458963) ; 北畠 健一朗 山形大学, 医学部, 医員 (60744456)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Project Status: Completed (Fiscal Year 2019)
• Budget Amount: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000); Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
• Keywords: 唾液 / 口腔癌 / 口腔潜在性悪性疾患 / 代謝物 / タンパク質 / 類似病変 / スクリーニング / 多層オミックス解析 / 口腔がん / 口腔前癌病変 / 口腔癌類似病変 / 口腔前癌病変類似病変 / メタボロミクス / プロテオミクス / トランスクリプトミクス / マルチオミックス

Outline of Final Research Achievements

Our aim is to identify salivary biomarkers to differentiate patients with oral cancer and oral potentially malignant disorders(OC/OPMD) from those with mimic benign oral mucosal lesions(MBOML) of OC/OPMD. Whole unstimulated saliva samples were collected from patients with OC (n=56), OPMD(leukoplakia:n=29, lichen:n=26) and MBOML(severe and moderate periodontitis:n=80). Metabolites and proteins in the saliva samples were comprehensively analyzed by capillary electrophoresis mass spectrometry and liquid chromatograph-mass spectrometry. To evaluate the discrimination ability of a combination of multiple markers, a multiple logistic regression (MLR) model was developed to differentiate OC/OPMD from MBOML of OC/OPMD. Ornithine and polyamines such as spermine and spermidine were significantly different between OC/OPMD and MBOML. The combination of these three metabolites showed a high area under the receiver operating characteristic curve over 80 % for discriminating OC/OPMD from MBOML.

Academic Significance and Societal Importance of the Research Achievements

唾液は非侵襲に取得できるため、疾患検査が確立すれば医療機関以外でも採取・検査が可能となり、応用範囲が非常に広い。本研究では唾液中のオルニチン、スペルミン、スペルミジンなどが、口腔癌・口腔潜在的悪性疾患患者とそれらの類似疾患患者とでは大きく異なることを明らかにし、また高い判別能を有することを明らかにした。これまで口腔癌や口腔潜在的悪性疾患をスクリーニングする方法は、視診と触診であり、それらの方法は歯科医師の経験によって大きく精度が異なっていた。唾液中の物質を用いて、口腔癌や口腔潜在的悪性疾患をスクリーニングできれば、非侵襲的で簡便そして客観的で高精度な検査になりうる。

Research Products

• [Journal Article] Discrimination of oral squamous cell carcinoma from oral lichen planus by salivary metabolomics (2019)
  • Author(s): Ishikawa Shigeo、Sugimoto Masahiro、Edamatsu Kaoru、Sugano Ayako、Kitabatake Kenichiro、Iino Mitsuyoshi
  • Journal Title: Oral Diseases Volume: 26 Issue: 1 Pages: 35-42
  • DOI: 10.1111/odi.13209
  • Peer Reviewed / Open Access
• [Journal Article] Identification of salivary metabolites for oral squamous cell carcinoma and oral epithelial dysplasia screening from persistent suspicious oral mucosal lesions (2018)
  • Author(s): Ishikawa Shigeo、Wong David T. W.、Sugimoto Masahiro、Gleber-Netto Frederico Omar、Li Feng、Tu Michael、Zhang Yong、Akin David、Iino Mitsuyoshi
  • Journal Title: Clinical Oral Investigations Volume: ‐ Issue: 9 Pages: 3557-3563
  • DOI: 10.1007/s00784-018-2777-3
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Discovery and Validation of Salivary Extracellular RNA Biomarkers for Noninvasive Detection of Gastric Cancer (2018)
  • Author(s): Li F、Yoshizawa JM.、Kim KM、Kanjanapangka J、Grogan TR.、Wang X、Elashoff DE.、Ishikawa S、Chia D、Liao W、Akin D、Yan X、Lee MS、Choi R、Kim SM、Kang SY、Bae JM、Sohn TS、Lee JH、Choi MG、Min BH、Lee Jun-Haeng、Kim JJ.、Kim Y、Kim S、Wong DT.W.
  • Journal Title: Clinical Chemistry Volume: 64 Issue: 10 Pages: 1513-1521
  • DOI: 10.1373/clinchem.2018.290569
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Effect of timing of collection of salivary metabolomic biomarkers on oral cancer detection (2017)
  • Author(s): Shigeo Ishikawa, Masahiro Sugimoto, Kenichiro Kitabatake, Micheal Tu, Ayako Sugano, Iku Yamamori, Asuka Iba, Kazuyuki Yusa, Miku Kaneko, Sana Ota, Kana Hiwatari, Ayame Enomoto, Tomita Masaru, Mitsuyoshi Iino
  • Journal Title: Amino Acids Volume: 49 Issue: 4 Pages: 761-770
  • DOI: 10.1007/s00726-017-2378-5
  • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
• [Presentation] 唾液中代謝物による口腔がんスクリーニングに関する研究 (2017)
  • Author(s): 石川恵生 北畠健一朗 菅野絢子 山森郁 遊佐和之 飯野光喜
  • Organizer: 第62回日本口腔外科学会総会・学術大会
• [Presentation] 唾液中代謝物を測定する際の唾液採取条件に関する研究～口腔癌スクリーニングのために～ (2017)
  • Author(s): 石川恵生 北畠健一朗 菅野絢子 山森郁 井場明日香 遊佐和之 橘寛彦 飯野光喜
  • Organizer: 第71回日本口腔科学会学術集会