Establishment of a model for risk stratification of lung cancer development by comprehensive analysis of oral mucosal gene abnormalities

• Project/Area Number: 17K10807
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Respiratory surgery
• Research Institution: Higashihiroshima Medical Center
• Principal Investigator: Harada Hiroaki 独立行政法人国立病院機構東広島医療センター(臨床研究部), 診療部呼吸器外科, 呼吸器外科医師 (90573816)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Project Status: Completed (Fiscal Year 2019)
• Budget Amount: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000); Fiscal Year 2019: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); 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: エピジェネティクス / 肺癌 / 分子マーカー / 遺伝子異常 / 口腔粘膜 / バイオマーカー / 外科

Outline of Final Research Achievements

We aimed to establish a biomarker that efficiently selects a high-risk group of lung cancer at low risk by comprehensive analysis of genetic abnormalities using the easily collectable oral mucosa, which is the airway tissue same as lung cancer tissue. An integrated analysis of epigenetics abnormalities, the main mechanism of cancer development, revealed the possibility that a combination of epigenetic alteration profile could be a promising molecular biological marker for lung cancer risk stratification.

Academic Significance and Societal Importance of the Research Achievements

肺がんの死亡率低下をもたらすが被爆リスクやコスト面、さらには偽陽性率の高さで問題を残すCT検診において、対象者とすべき肺がん発生高リスク群の選定が現在大きな課題である。
肺組織の採取に比べ口腔粘膜の採取は極めて容易で危険性も少ないため、口腔粘膜の解析による肺がん発生高リスク群の選出についてその可能性を示すことができた本研究は、今後社会全体として低リスク低コストである効率的な肺がん検診システムの構築に繋がる学術的・社会的な意義を有するものと考える。

Research Products

• [Journal Article] Lung cancer risk stratification using methylation profile in the oral epithelium (2019)
  • Author(s): Hiroaki Harada, et al.
  • Journal Title: Asian Cardiovasucular and Thoracic Annals Volume: 27 Issue: 2 Pages: 87-92
  • DOI: 10.1177/0218492318813443
  • Peer Reviewed
• [Presentation] Assessment of inter-tumor heterogeneity among primary and metastatic lesions in a patient with untreated lung cancer by DNA methylation profiling: an autopsy case (2019)
  • Author(s): Hiroaki Harada, et al.
  • Organizer: 24th Congres of the Asian PacifiSociety of Respirology
  • Int'l Joint Research
• [Presentation] 口腔粘膜遺伝子エピジェネティクス異常解析による肺癌発生リスク層別化の試み (2019)
  • Author(s): 原田洋明、他
  • Organizer: 第36回 日本呼吸器外科学会 学術総会
• [Presentation] 肺癌無治療例における剖検検体を用いた病巣別p16エピジェネティクス異常プロファイルの検討 (2019)
  • Author(s): 原田洋明、他
  • Organizer: 第60回 日本肺癌学会総会
• [Presentation] Clinical relevance between preoperative serum oxidative stress level and aberrant DNA methylation of peripheral whole blood in patients with curatively resected Stage I lung adenocarcinoma; A pilot analysis. (2018)
  • Author(s): Narumi Yashiki, Hiroaki Harada, et al
  • Organizer: 23rd Congress of the Asian Pacific Society of Respirology
  • Int'l Joint Research
• [Presentation] Clinical implication of DNA methylation analysis in the oral epithelium for lung cancer risk stratification (2018)
  • Author(s): Hiroaki Harada, et al.
  • Organizer: 23rd Congress of the Asian Pacific Society of Respirology
  • Int'l Joint Research
• [Presentation] Preoperative serum oxidative stress levels are associated with aberrant PCDH10 methylation in serum and poor clinical outcomes in curatively resected node-negative non-small cell lung cancer (2017)
  • Author(s): Hiroaki Harada, et al.
  • Organizer: Asia Pacific Society of Respirology
  • Int'l Joint Research
• [Presentation] Combined Analysis of Epigenetic Inactivation of MDFI, DLX4, and PCDH10 in Stage I Non-Small Cell Lung Cancer for the Assessment of Prognostic Impact (2017)
  • Author(s): Hiroaki Harada, et al.
  • Organizer: World Congress of Surgery
  • Int'l Joint Research
• [Presentation] 口腔粘膜遺伝子エピジェネティクス異常を用いた肺癌発生リスク評価の試み (2017)
  • Author(s): 原田洋明 他
  • Organizer: 日本胸部外科学会定期学術集会