DNA methylation and IDH mutations in intrahepatic cholangiocarcinoma
| Project/Area Number |
20K16418
|
|---|
| 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 | Kumamoto University |
|---|
Principal Investigator |
Miyata tatsunori 熊本大学, 生命科学研究部(医), 特定研究員 (80594887)
|
|---|
| Project Period (FY) |
2020-04-01 – 2022-03-31
|
| Project Status |
Completed (Fiscal Year 2021)
|
| Budget Amount *help |
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2021: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2020: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
|
|---|
| Keywords | 肝内胆管癌 / LINE-1 / DNAメチル化 / エピジェネティクス / IDH変異 / IDH |
|---|
| Outline of Research at the Start |
熊本大学病院におけるICCの切除サンプルを用いて、パイロシークエンス法にてLINE-1のメチル化及びIDH変異の有無について検討を行う。得られた結果を元に、LINE-1のメチル化及びIDH変異の有無と臨床病理学的背景 (年齢、性別、腫瘍マーカー、腫瘍の大きさ、リンパ節転移、脈管侵襲の有無、進行度等)及び肝切除後の予後との関連を統合的に解析する。さらに、LINE-1のメチル化レベルとIDH変異の相互の関連についても併せて評価する。この成果は、LINE-1、IDHの地位の確立と新たな治療ターゲットの発見につながり、ICCの予後予測及び予後改善に重要な意義を持つと考える。
|
| Outline of Final Research Achievements |
Methylation of LINE-1 promoter region in cancerous and noncancerous areas was measured in resected samples of intrahepatic cholangiocarcinoma (ICC). In the analysis of clinicopathologic factors and LINE-1 methylation levels, the hypomethylated group had a significantly higher frequency of lymph node metastases (p=0.04) and a significantly worse prognosis in overall survival (Log-rank p=0.045), but there was no difference between the two groups in recurrence-free survival.
IDH mutations (IDH1 and IDH2) were found in 9 of 72 patients (12.5%), including 8 patients (11.1%) with IDH1 mutation and 1 patient (1.4%) with IDH2 mutation. The relationship between clinicopathological factors and IDH mutations was evaluated in the 67 patients for whom patient information was available, and no statistically significant differences in clinicopathological factors, prognosis, or LINE-1 methylation levels were found between the two groups.
|
| Academic Significance and Societal Importance of the Research Achievements |
ICCは予後不良な肝がんの一組織型である。術後も早期に再発することから、その予後を予測し再発や予後が不良なICCを同定することは重要である。本研究により、ICCのLINE-1メチル化が低い症例はリンパ節転移が有意に多く、肝切除後の予後が悪かった。しかしながら、IDH変異との関連は示されなかった。より大きなサンプルを用いてLINE-1メチル化を用いたICCの予後予測についてさらなる検討が必要である。
|
Report
(3 results)
Research Products
(18 results)
-
-
-
-
-
-
-
-
[Journal Article] Metabolic shift to serine biosynthesis through 3-PG accumulation and PHGDH induction promotes tumor growth in pancreatic cancer2021
Author(s)
Itoyama R, Yasuda-Yoshihara N, Kitamura F, Yasuda T, Bu L, Yonemura A, Uchihara T, Arima K, Hu X, Jun Z, Okamoto Y, Akiyama T, Yamashita K, Nakao Y, Yusa T, Kitano Y, Higashi T, Miyata T, Imai K, Hayashi H, Yamashita Y, Mikawa T, Kondoh H, Baba H, Ishimoto T
-
Journal Title
Cancer Letters
Volume: 523
Pages: 29-42
DOI
Related Report
Peer Reviewed / Open Access
-
-
-
-
[Journal Article] Differential role of MLKL in alcohol-associated and non?alcohol-associated fatty liver diseases in mice and humans2021
Author(s)
Miyata T, Wu X, Fan X, Huang E, Sanz-Garcia C, Ross CKC, Roychowdhury S, Bellar A, McMullen MR, Dasarathy J, Allende DS, Caballeria J, Sancho-Bru P, McClain CJ, Mitchell M, McCullough AJ, Radaeva S, Barton B, Szabo G, Dasarathy S, Nagy LE
-
Journal Title
JCI Insight
Volume: 6
Issue: 4
DOI
Related Report
Peer Reviewed / Open Access
-
-
-
-
-
-
