Search for novel biomarkers to predict treatment sensitivity in colorectal cancer

• Project/Area Number: 18K15263
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 50020:Tumor diagnostics and therapeutics-related
• Research Institution: Tohoku University
• Principal Investigator: Ouchi Kota 東北大学, 大学病院, 助教 (50781291)
• Project Period (FY): 2018-04-01 – 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 2019: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000); Fiscal Year 2018: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
• Keywords: DNAメチル化 / 大腸癌 / 抗EGFR抗体薬 / バイオマーカー / 遺伝子発現

Outline of Final Research Achievements

CpG sites associated with 355 genes with altered methylation status between normal colonic mucosa and tumor tissue in the HMCC group were extracted. When comparing the HMCC and LMCC groups for the extracted CpG sites in a dataset of 139 cases, 62 genes containing regions that were specifically methylated only in the HMCC group were extracted. Alterations in gene expression due to changes in methylation status in some of these genes may be responsible for the difference in the sensitivity of anti-EGFR antibodies. Using a data set of 139 cases, we have looked for genes with significantly different expression statuses in 62 genes between the HMCC and LMCC groups, but did not identify any genes that were significantly different between the two groups.

Academic Significance and Societal Importance of the Research Achievements

大腸癌のおよそ20%程度に高頻度にメチル化を認める症例群が含まれ、高メチル化大腸癌と低メチル化大腸癌とでは疫学的、分子生物学的特徴が異なることが広く知られている。しかし、現状でメチル化状態によって大腸癌の予後や薬剤感受性が異なることを説明可能な分子生物学的機序は明らかになっていない。本研究ではHMCCの腫瘍組織と正常大腸粘膜の比較、さらにHMCCとLMCCとの比較を行うことで、高メチル化大腸癌で特異的にメチル化されている領域を明らかにした。今後、スプライシングバリアントを加味した解析を追加することで、メチル化によって大腸癌の予後や薬剤感受性が変化する機序が明らかとなる可能性がある。