Exploring the mechanism by which BUB1 confers malignant potential in utothelial carcinoma
Project/Area Number |
17K16821
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Research Category |
Grant-in-Aid for Young Scientists (B)
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Allocation Type | Multi-year Fund |
Research Field |
Urology
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Research Institution | Osaka Medical College |
Principal Investigator |
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Project Period (FY) |
2017-04-01 – 2019-03-31
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Project Status |
Completed (Fiscal Year 2018)
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Budget Amount *help |
¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000)
Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2017: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000)
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Keywords | 膀胱癌 / DNAダメージ / 膀胱がん |
Outline of Final Research Achievements |
TMT-based quantification analysis between treatment-naive and chemo-radiation resistant tumors identified 1640 proteins. We confirmed that GO term analysis of UniProtKB key words for upregulated proteins exhibited significantly upregulated DNA damage repair pathways and revealed that BUB1 (budding uninhibited by benzimidazoles 1) is the most significantly upregulated protein in chemo-resistant clones compared to treatment-naive tumor. We next developed experimental model to analyze the function of aberrant BUB1 expression upon DNA damage using digital droplet PCR and CRISPR-Cas9 system and revealed that upregulation of BUB1 activated alternative non-homologous end joining repair creating deletion and insertion sites at double strand break. In dataset analysis, upregulation of BUB1 is associated with poor outcome and notably, there was a significant correlation between increased BUB1 expression and tumor mutation burden suggesting the link to the effect of immune-checkpoint inhibition.
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Academic Significance and Societal Importance of the Research Achievements |
現在国内で行われているゲノム医療の普及促進の一つの課題として、解析後のアウトプットとなる臨床治験を含む治療選択肢の拡充が挙げられると考えている。癌治療、研究において特定のKey Moleculeによる多彩な形質変化を明らかにすることは、患者様の発現差異による層別化を可能にし、さらにその変化に伴う治療ターゲットの発見がテーラーメード医療を可能にする。本研究においてもBUB1 inhibitorによる治療効果予測因子を明らかにすることにより、個別化医療Precision Medicineへの発展を目指すとともに、来るべきゲノム医療で加療選択され得る治療オプションの一つとなる可能性を明らかにしたい。
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Report
(3 results)
Research Products
(14 results)
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[Journal Article] hibition controls aggressive prostate tumors deficient in Y-linked histone demethylase KDM5D.2018
Author(s)
Komura K、Yoshikawa Y, Shimamura T, Chakraborty G, Gerke TA, Hinohara K, Chadalavada K, Jeong SH, Armenia J, Du SY, Mazzu YZ, Taniguchi K, Ibuki N, Meyer CA, Nanjangud GJ, Inamoto T, Lee GM, Mucci LA, Azuma H, Sweeney CJ, Kantoff PW.
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Journal Title
Journal of Clinical Investigation
Volume: 128(7)
Issue: 7
Pages: 2979-95
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] SRSF3, a Splicer of the PKM Gene, Regulates Cell Growth and Maintenance of Cancer-Specific Energy Metabolism in Colon Cancer Cells.2018
Author(s)
Kuranaga Y, Sugito N, Shinohara H, Tsujino T, Taniguchi K, Komura K, Ito Y, Soga T, Akao Y.
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Journal Title
Int J Mol Sci.
Volume: 19
Issue: 10
Pages: 3012-3012
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Preoperative Measurement of the Modified Glasgow Prognostic Score Predicts Patient Survival in Non-Metastatic Renal Cell Carcinoma Prior to Nephrectomy.2017
Author(s)
Tsujino T,Komura K, Matsunaga T, Yoshikawa Y, Takai T, Uchimoto T, Saito K, Tanda N, Oide R, Minami K, Uehara H, Jeong SH, Taniguchi K, Hirano H, Nomi H, Ibuki N, Takahara K, Inamoto T, Azuma H.
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Journal Title
Ann Surg Oncol.
Volume: 24(9)
Issue: 9
Pages: 2787-93
DOI
Related Report
Peer Reviewed
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[Journal Article] The combination of preoperative platelet count and neutrophil lymphocyte ratio as a prognostic indicator in localized renal cell carcinoma.2017
Author(s)
Takuya Tsujino,Kazumasa Komura, Atsushi Ichihashi, Takeshi Tsutsumi,Tomohisa Matsunaga, Yuki Yoshikawa, Ryoichi Maenosono, Kyohei Okita,Tomoaki Takai, Rintaro Oide, Koichiro Minami, Hirofumi Uehara, Kohei Taniguchi, Hajime Hirano, Hayahito Nomi, Naokazu Ibuki, Kiyoshi Takahara,Teruo Inamoto, Haruhito Azuma.
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Journal Title
Oncotarget
Volume: 8
Issue: 66
Pages: 110311-25
DOI
Related Report
Peer Reviewed
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[Journal Article] The systemic inflammation-based Glasgow Prognostic Score as a powerful prognostic factor in patients with upper tract urothelial carcinoma.2017
Author(s)
Inamoto T,Matsuyama H, Sakano S, Ibuki N, Takahara K, Komura K, Takai T, Tsujino T, Yoshikawa Y, Minami K, Nagao K, Inoue R, Azuma H.
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Journal Title
Oncotarget
Volume: 8(68)
Issue: 68
Pages: 113248-57
DOI
Related Report
Peer Reviewed
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