Epigenetic diagnosis and therapy for thymic carcinoma

2022 Fiscal Year Final Research Report

• Project/Area Number: 20K09178
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 55040:Respiratory surgery-related
• Research Institution: The University of Tokushima
• Principal Investigator: KONDO Kazuya 徳島大学, 大学院医歯薬学研究部(医学域), 教授 (10263815)
• Co-Investigator(Kenkyū-buntansha): 吉田 光輝 徳島大学, 病院, 講師 (30403710) ; 宮本 直輝 徳島大学, 病院, 助教 (00865305)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: 胸腺癌 / DNAメチル化 / 網羅的解析 / CpGサイト / 癌抑制遺伝子

Outline of Final Research Achievements

We performed genome wide screening of methylated CpG islands in thymoma and thymic carcinoma. We identified 92 CpG islands significantly hypermethylated in thymic carcinoma in relation to thymoma and selected GNG4, GHSR, HOXD9, SALL3, GAD1, NPTX2 and MT1 which are related to cancer. We examined the methylation, mRNA and protein expression. Methylation was significantly higher in thymic carcinoma than in thymoma and revealed a high discrimination between thymic carcinoma and thymoma in all 7 genes. Among the 7 genes, relapse free survival was significantly worse in tumors with a higher DNA methylation than in those with a lower DNA methylation.
In GAD1, mRNA and protein expression were significantly higher in thymic carcinoma than in thymomas. Tumors with high GAD1 DNA methylation and high mRNA and protein expression had significantly shorter relapse free survival rates than those with low levels. It acts as oncogenic function.

Free Research Field

呼吸器外科学

Academic Significance and Societal Importance of the Research Achievements

胸腺癌は、難治性であり、治療薬も限定されている。新薬を発見するため、新しいアプローチが必要である。私たちの研究は、網羅的にDNAメチル化を解析し、胸腺癌が“ エピジェネティック（遺伝子変化を伴わない遺伝子発現の変化）な異常を多く有する腫瘍”であることを示した。特に、GAD1遺伝子は、DNAのメチル化頻度と蛋白発現が相関し、腫瘍の悪性度と関連する。治療の候補分子となることが推測された。