2022 Fiscal Year Final Research Report
Epitranscriptomic alteration in soft tissue sarcoma
| Project/Area Number |
21K20805
|
|---|
| Research Category |
Grant-in-Aid for Research Activity Start-up
|
| Allocation Type | Multi-year Fund |
|---|
| Review Section |
0901:Oncology and related fields
|
|---|
| Research Institution | Kyushu University |
|---|
Principal Investigator |
|
|---|
| Project Period (FY) |
2021-08-30 – 2023-03-31
|
| Keywords | 軟部肉腫 |
|---|
| Outline of Final Research Achievements |
We analyzed soft-tissue leiomyosarcoma using RNA-seq and genome sequencing data.
RNA-seq showed that patients with high expression of METTL3 gene, an RNA methyltransferase, tended to have a poorer prognosis than those with low expression. Gene mutation analysis showed amplification of the ALKBH5 gene in 17% of cases. Immunostaining of tumor tissue samples showed that high expression of METTL3, WTAP, and ALKBH5 was associated with significantly more Mitosis than low expression; PD-L1 expression was significantly more common in high METTL3 expression and YTHDF2 expression.
Combinate inhibition of epitranscriptome modifying enzymes and checkpoint molecules may be a novel therapeutic target.
|
| Free Research Field |
病理学
|
| Academic Significance and Societal Importance of the Research Achievements |
軟部平滑筋肉腫は、有効な治療薬が少なく予後不良の疾患である。近年、腫瘍シグナル伝達経路、免疫チェックポイント分子を標的とした治療が、短期間の無増悪生存は得られるものの、根治は困難である。
近年、遺伝子発現を調整する因子として、RNAの翻訳後修飾がRNAの安定化、分解促進に寄与するエピトランスクリプトームという概念が登場した。我々は、RNAメチル化酵素の遺伝子異常を解析し、ALKBH5遺伝子増幅を見出した。免疫染色でALKHBH5高発現、METTL3高発現は、低発現と比べて、有意に核分裂数が多かった。以上から、RNAメチル化酵素METTL3、ALKBH5の阻害は新規治療標的となることが示唆された。
|
