Prediction of outcomes and response to treatments with an ultrasensitive method for assessing intratumor epigenetic heterogeneity in colorectal cancer

• Project/Area Number: 16K19957
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Digestive surgery
• Research Institution: Juntendo University
• Principal Investigator: Sugimoto Kiichi 順天堂大学, 医学部, 准教授 (30407275)
• Project Period (FY): 2016-04-01 – 2020-03-31
• Project Status: Completed (Fiscal Year 2019)
• Budget Amount: ¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000); Fiscal Year 2018: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000); Fiscal Year 2017: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2016: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
• Keywords: 大腸癌 / DNAメチル化 / p14 / リキッドバイオプシー / 予後予測因子 / エピジェネティクス / 循環血漿DNA / バイオマーカー

Outline of Final Research Achievements

Eighty-six patients, who had undergone resection of adenocarcinoma of the colon and rectum, were enrolled in this study. The patient backgrounds, clinicopathological factors and gene promoter methylation status were analyzed. Quantitative methylation-specific PCR (qMSP) was performed using the bisulfite-modified DNA for p14 gene promoter methylation.
In univariate analysis, the patients with venous invasion had significantly higher RMVs of p14 gene compared with those without (p=0.009).Similarly, the patients with lung metastases had significantly higher RMVs of p14 gene compared with those without lung metastases (p=0.007). There were no significant correlations between RMVs of p14 and other clinicopathological factors. Our current study demonstrated the correlations between the promoter methylation status of p14 tumor suppressor genes in cell-free DNA from plasma and hematogeneous metastasis, especially lung metastasis.

Academic Significance and Societal Importance of the Research Achievements

本研究の目的は，癌患者の血漿DNAメチル化を解析し，予後予測因子としての意義を探求し確立することである．DNAメチル化は，癌の発生や進行に重要な役割を果たし，これまで多くの遺伝子のDNAメチル化が同定されてきた．さらに近年では，癌組織におけるDNAメチル化の不均一性も指摘され，その不均一性と，同じ癌腫における異なる悪性度や，治療抵抗性における多様性との関連が示唆されている．本研究は，大腸癌のDNAメチル化の解析を行うことで．血漿のDNAメチル化の程度が予後に与える影響を明らかにした重要性の高い研究である．

Research Products

• [Int'l Joint Research] Johns Hopkins University(米国)
• [Int'l Joint Research] ジョンズ・ホプキンス大学(米国)
• [Presentation] Circulating Plasma DNA Methylation Status of Tumor Suppressor Genes May be A Biomarker of Lung Metastasis in Colorectal Cancer (2019)
  • Author(s): 杉本 起一
  • Organizer: 2020 DDW
  • Int'l Joint Research
• [Presentation] 大腸癌における癌抑制遺伝子の血漿中遊離DNAメチル化測定の意義 (2019)
  • Author(s): 杉本 起一
  • Organizer: 2020年 日本消化器外科学会総会
• [Presentation] 大腸癌における血漿中遊離DNAメチル化測定の意義 (2018)
  • Author(s): 杉本起一
  • Organizer: 日本消化器外科学会