Functional analysis of DDX41 for the construction of new therapeutic strategies in the era of renal cancer immunotherapy.

2023 Fiscal Year Final Research Report

• Project/Area Number: 20K18143
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 56030:Urology-related
• Research Institution: Hiroshima University
• Principal Investigator: Hieda Keisuke 広島大学, 病院(医), 講師 (60625630)
• Project Period (FY): 2020-04-01 – 2024-03-31
• Keywords: 腎細胞癌 / DDX41 / ケモカイン / 予後予測因子

Outline of Final Research Achievements

It is known that the presence of tumor necrosis within renal cell carcinoma is associated with a higher malignancy. However, the underlying mechanisms have not been well understood. Our group hypothesized that the expression of a protein called DDX41, which detects intracellular DNA degraded by tumor necrosis, might be related to cancer malignancy. Using tissue samples from patients who underwent surgery for renal cell carcinoma, we evaluated the expression levels of DDX41. We found that higher expression levels of DDX41 were associated with increased recurrence rates and poorer survival outcomes.

Free Research Field

腎細胞癌

Academic Significance and Societal Importance of the Research Achievements

これまで、腎細胞癌における腫瘍壊死が、なぜ悪性度や予後増悪に関与するのか未知の点が多かった。我々は、腫瘍壊死により放出される分解されたdsDNAをDDX41が感知して発現が上昇し、間接的に予後増悪に寄与すると考えた。本研究は、腎細胞癌のうち最も頻度の高い淡明細胞型腎細胞癌において、DDX41 の発現が腫瘍壊死や生命予後と有意に関係している事を初めて明らかにした。淡明細胞型腎細胞癌はVHL機能欠失型変異を特徴とするが、VHL欠失下においてのみ、DDX41の発現上昇はケモカインファミリーの発現亢進や腫瘍増殖に寄与する事が判明した。DDX41の高発現は、淡明細胞型腎細胞癌の予後予測因子となる。