| Project/Area Number |
22K20943
|
|---|
| Research Category |
Grant-in-Aid for Research Activity Start-up
|
| Allocation Type | Multi-year Fund |
|---|
| Review Section |
0905:Surgery of the organs maintaining homeostasis and related fields
|
|---|
| Research Institution | Kyushu University |
|---|
Principal Investigator |
|
|---|
| Project Period (FY) |
2022-08-31 – 2024-03-31
|
| Project Status |
Completed (Fiscal Year 2023)
|
| Budget Amount *help |
¥2,860,000 (Direct Cost: ¥2,200,000、Indirect Cost: ¥660,000)
Fiscal Year 2023: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2022: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
|
|---|
| Keywords | スキルス胃癌 / CAF / DDS / シングルセル遺伝子発現解析 / 癌関連線維芽細胞(CAF) / heterogeneity / 炎症性CAF |
|---|
| Outline of Research at the Start |
近年、膵癌における癌関連線維芽細胞(Cancer-associated fibroblast; CAF)のheterogeneityが報告されたが、スキルス胃癌のheterogeneityを明らかにした報告はなく、スキルス胃癌CAFが腫瘍微小環境に与える詳細については明らかになっていない。スキルス胃癌では全身化学療法の継続が重要であり、有害事象のコントロールが治療継続の鍵になっている。本研究ではスキルス胃癌CAFのサブタイプの一つである炎症性CAFの腫瘍促進関連分子を標的とし、腫瘍特異的に治療薬を伝送するという、全く新しいスキルス胃癌CAF標的治療の開発を目的とする。
|
| Outline of Final Research Achievements |
We performed scRNA-seq focusing on noncomplex poorly differentiated gastric adenocarcinomas (por2), including scirrhous gastric carcinomas. We identified myofibrillary and inflammatory CAFs previously reported in por2 gastric cancer CAFs. Furthermore, the proportion of clusters with high gene expression characteristic of myofibrillary CAFs was higher than that of non-por2 gastric cancers, and pathways involved in cell proliferation were significantly elevated. The heterogeneity of CAFs in por2 gastric cancers suggested that myofibrillary CAFs may suppress CD8-positive T cell infiltration into the tumor. GSEA analysis showed significantly higher neurotransmitter receptor activity in por2 gastric carcinoma, identifying potential therapeutic target molecules among the core enrichment genes.
|
| Academic Significance and Societal Importance of the Research Achievements |
近年、scRNA-seqを用いた研究で、膵癌には筋線維性CAF、炎症性CAF、抗原提示CAFが存在することが報告され、さらに大腸癌では炎症性CAFが予後不良因子であることが示された。しかし、スキルス胃癌CAFのheterogeneityの報告はこれまでにない。
|
