Development of a novel therapeutic strategy and prediction of therapeutic response for treatment-resistant bladder cancer by exosomes

2023 Fiscal Year Final Research Report

• Project/Area Number: 22K16792
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 56030:Urology-related
• Research Institution: Kagoshima University
• Principal Investigator: INOGUCHI Satoru 鹿児島大学, 医歯学域鹿児島大学病院, 助教 (60735364)
• Project Period (FY): 2022-04-01 – 2024-03-31
• Keywords: 膀胱癌 / 治療抵抗 / エクソソーム

Outline of Final Research Achievements

As research results, we performed sequencing analysis using RNA in serum exosomes of bladder urothelial carcinoma, bladder cancer CIS, and renal pelvis ureteral urothelial carcinoma derived from patients and confirmed that the pattern of nucleic acids in exosomes is significantly different in urothelial carcinoma compared with normal samples. Next, we focused on BYCRN1, one of the LncRNAs among the candidate nucleic acids, and investigated its expression in serum exosomal RNAs, and found that its expression was significantly increased in patients with urothelial carcinoma compared to healthy controls. Furthermore, knockdown of BYCRN1 showed an antitumor effect. In addition, looking at the expression in pre- and postoperative samples, it was found that the expression was decreased after surgery. These results are summarized in the paper.

Free Research Field

泌尿器癌

Academic Significance and Societal Importance of the Research Achievements

現在、臨床的に感度・特異度ともに有用な尿路上皮癌（腎盂尿管癌および膀胱癌）の腫瘍マーカーは無く、患者は放射線被曝を伴うCT検査や侵襲の大きな尿管鏡検査や膀胱鏡検査が一般的に行われている。更に画像検査や内視鏡検査で腫瘍の存在を確認するにはある程度腫瘍が大きくならないと判断できないのが現状である。そこで、エクソソーム含有核酸を用いて尿路上皮癌に対する腫瘍マーカーとなる核酸を検出することを本研究の目的としたが、我々の研究成果は血清エクソソーム中のBCYRN1が尿路上皮癌患者で有意に高く、また術後に発現が低下した。そのため、腫瘍マーカーの確立に向けて大きな一歩を踏み出したと考える。