Identification of factors associated with drug-therapy resistance by pheripheral blood serum cell-free nucleotic acids

• Project/Area Number: 26670695
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Urology
• Research Institution: Akita University
• Principal Investigator: Habuchi Tomonori 秋田大学, 医学(系)研究科(研究院), 教授 (00293861)
• Co-Investigator(Kenkyū-buntansha): 黄 明国 秋田大学, 医学(系)研究科(研究院), 助教 (60448503) ; 南條 博 秋田大学, 医学部, 准教授 (70250892) ; 大山 力 弘前大学, 医学研究科, 教授 (80282135)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000); Fiscal Year 2016: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2015: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2014: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
• Keywords: 腎癌 / 膀胱癌 / エキソソーム / 分子標的薬 / 液性生検 / PAI-1 / miR-21 / 腎細胞癌 / 尿路上皮癌 / microRNA / アキシチニブ / エクソソーム / miRNA / バイオマーカー / 泌尿器癌 / Liquid Biopsy / 前立腺癌 / DNA / RNA

Outline of Final Research Achievements

To explore candidate serum cell-free nucleotic acid or protein biomarkers associated with drug resistance in advanced urological cancers, we collected and analyzed the serum exosome RNA and proteins. As the results focusing on Axitinib therapy in advanced RCC patients, patients whose serum miR-21 level was decreased after Axitinib treatment had significantly better progression free survival. Patients whose serum PAI-1 level was decreased after Axitinib treatment had significantly better progression free survival and overall survival. In addition, the pre-treatment PAI-l level was significantly associated with the objective response rate.
In conclusion, the serum miR-21 level or PAI-1 protein level may be a promising biomarker in the Axitinib treatment for advanced RCC patients.

Research Products

• [Journal Article] The impact of obesity and adiponectin signaling in patients with renal cell carcinoma: A potential mechanism for the "obesity paradox". (2017)
  • Author(s): Ito R, Narita S, Huang M, Nara T, Numakura K, Takayama K, Tsuruta H, Maeno A, Saito M, Inoue T, Tsuchiya N, Satoh S, Habuchi T
  • Journal Title: PLoS One Volume: 12 Issue: 2 Pages: e0171615-e0171615
  • DOI: 10.1371/journal.pone.0171615
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Inhibition of the RANK/RANKL signaling with osteoprotegerin prevents castration-induced acceleration of bone metastasis in castration-insensitive prostate cancer (2017)
  • Author(s): 1)Takayama K, Inoue T, Narita S, Maita S, Huang M, Numakura K, Tsuruta H, Saito M, Maeno A, Satoh S, Tsuchiya N, Habuchi T
  • Journal Title: Cancer Letters Volume: in press Pages: 103-110
  • DOI: 10.1016/j.canlet.2017.03.034
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Altered miRNA expression in high-fat diet-induced prostate cancer progression. (2016)
  • Author(s): Nara T, Narita S, Mingguo H, Yoshioka T, Koizumi A, Numakura K, Tsuruta H, Maeno A, Saito M, Inoue T, Tsuchiya N, Satoh S, Habuchi T
  • Journal Title: Carcinogenesis Volume: 37 Pages: 1129-1137
  • DOI: 10.1093/carcin/bgw108
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Diet-induced alteration of fatty acid synthase in prostate cancer progression (2016)
  • Author(s): Huang M, Koizumi A, Narita S, Inoue T, Tsuchiya N, Nakanishi H, Numakura K, Tsuruta H, Saito M, Satoh S, Nanjo H, Sasaki T, Habuchi T
  • Journal Title: Oncogenesis Volume: ５ Issue: 2 Pages: e195-e195
  • DOI: 10.1038/oncsis.2015.42
  • Peer Reviewed / Open Access
• [Journal Article] INPP4B is a PtdIns(3,4,5)P3 phosphatase that can act as a tumor suppressor. (2015)
  • Author(s): Kofuji S, Kimura H, Nakanishi H, Nanjo H, Takasuga S, Liu H, Eguchi S, Nakamura R, Itoh R, Ueno N, Asanuma K, Huang M, Koizumi A, Habuchi T, Yamazaki M, Suzuki A, Sasaki J, Sasaki T
  • Journal Title: Cancer Discovery Volume: in press Issue: 7 Pages: 730-9
  • DOI: 10.1158/2159-8290.cd-14-1329
  • Peer Reviewed / Open Access
• [Journal Article] Risk Analysis of Prostate Cancer in PRACTICAL, a Multinational Consortium, Using 25 Known Prostate Cancer Susceptibility Loci (2015)
  • Author(s): Amin Al Olama A, Ingles SA, Habuchi T, et al. Kote-Jarai Z, Eeles RA, Easton DF
  • Journal Title: Cancer Epidemiol Biomarkers Prev Volume: 24 Issue: 7 Pages: 1121-1129
  • DOI: 10.1158/1055-9965.epi-14-0317
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Effects of functional genetic polymorphisms in the CYP19A1 gene on prostate cancer risk and survival (2015)
  • Author(s): Kanda S, Tsuchiya N, Narita S, et al.
  • Journal Title: Int J Cancer Volume: 136 Issue: 1 Pages: 74-82
  • DOI: 10.1002/ijc.28952
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Lymphovascular invasion is significantly associated with biochemical relapse after radical prostatectomy even in patients with pT2N0 negative resection margin (2014)
  • Author(s): Mitsuzuka K, Narita S, Koie T, Kaiho Y, Tsuchiya N, Yoneyama T, Kakoi N, Kawamura S, Tochigi T, Ohyama C, Habuchi T, Arai Y
  • Journal Title: Prostate Cancer Prostatic Dis Volume: ePub Issue: 1 Pages: 25-30
  • DOI: 10.1038/pcan.2014.40
  • Peer Reviewed
• [Journal Article] Serum tri-and tetra-antennary N-glycan is a potential predictive biomarker for castration-resistant prostate cancer. (2014)
  • Author(s): Ishibashi Y, Tobisawa Y, Hatakeyama S, Ohashi T, Tanaka M, Narita S, Koie T, Habuchi T, Nishimura S, Ohyama C, Yoneyama T
  • Journal Title: Prostate Volume: 74 Issue: 15 Pages: 1521-1529
  • DOI: 10.1002/pros.22869
  • Peer Reviewed / Open Access
• [Journal Article] Reassessment of prognostic heterogeneity of pT3 renal pelvic urothelial carcinoma: analysis in terms of proposed pT3 subclassification systems. (2014)
  • Author(s): Park J, Habuchi T, Arai Y, Ohyama C, Inoue T, Hatakeyama S, Jeon SS, Kwon GY, Kwak C, Moon KC, Kim CS, Ahn H.
  • Journal Title: J Urol. Volume: 192 Issue: 4 Pages: 1064-1071
  • DOI: 10.1016/j.juro.2014.04.001
  • Peer Reviewed
• [Journal Article] Organ-specific and tumor-size-dependent responses to sunitinib in clear cell renal cell carcinoma (2014)
  • Author(s): Tsuchiya N, Yuasa T, Maita S, Narita S, Inoue T, Numakura K, Saito M, Satoh S, Yonese J, Habuchi T
  • Journal Title: BMC Urology Volume: 14 Issue: 1 Pages: 26-26
  • DOI: 10.1186/1471-2490-14-26
  • Peer Reviewed
• [Journal Article] Measurement of aberrant glycosylation of prostate specific antigen can improve specificity in early detection of prostate cancer. (2014)
  • Author(s): Yoneyama T, Ohyama C, Hatakeyama S, Narita S, Habuchi T, Koie T, Mori K, Hidari KI, Yamaguchi M, Suzuki T, Tobisawa Y
  • Journal Title: Biochem Biophys Res Commun. Volume: 448 Issue: 4 Pages: 390-396
  • DOI: 10.1016/j.bbrc.2014.04.107
  • Peer Reviewed / Open Access
• [Presentation] MiR-130a modulates high-fat diet-induced prostate cancer progression through the activation of MET (2016)
  • Author(s): Taketoshi Nara, Shintaro Narita, Huang Mingguo, Toshiaki Yoshioka, Koichiro Takayama, Kazuyuki Numakura, Hiroshi Tsuruta, Atsushi Maeno, Mitsuru Saito, Takamitsu Inoue, Shigeru Satoh, Tomonori Habuchi
  • Organizer: Annual Meeting of American Urological Association 2016
  • Place of Presentation: SanDiego, California, USA
  • Year and Date: 2016-05-06
  • Int'l Joint Research
• [Presentation] Expression of steroid hormone receptors in residual cancer and stromal cells after neoadjuvant chemohormonal therapy with docetaxal for high-risk localized prostate cancer (2016)
  • Author(s): Shintaro Narita, Taketoshi Nara, Mingguo Huang, Koichiro Takayama, Kazuyuki Numakura, Hiroshi Tsuruta, Atsushi Maeno, Mitsuru Saito, Takamitsu Inoue, Norihiko Tsuchiya, Hiroshi Nanjo, Shigeru Satoh, Tomonori Habuchi
  • Organizer: Annual Meeting of American Urological Association 2016
  • Place of Presentation: SanDiego, California, USA
  • Year and Date: 2016-05-06
  • Int'l Joint Research
• [Presentation] Stabilization of invadopodia by plectin- mediated conjunction to vimentin intermediate filament is a critical molecular step of invasion and extravasation for metastasis in bladder cancer (2016)
  • Author(s): Mihoko Sutoh Yoneyama, Shingo Hatakeyama, Tomonori Habuchi, Takamitsu Inoue, Toshiya Nakamura, Tomihisa Funyu, Gerhard Wiche, Shigeru Tsuboi, Chikara Ohyama
  • Organizer: Annual Meeting of American Urological Association 2016
  • Place of Presentation: SanDiego, California, USA
  • Year and Date: 2016-05-06
  • Int'l Joint Research
• [Presentation] Exosomal miRNAs and serum cytokines as predictors for treatment outcomes in patients with metastatic renal cell carcinoma treated with axitinib (2016)
  • Author(s): Naoko Suzuki-Honma*, Akita, Japan, Norihiko Tsuchiya, Yamagata, Japan, Takamitsu Inoue, Shintaro Narita, Mitsuru Saito, Hiroshi Tsuruta, Atsushi Maeno, Shigeru Satoh, Tomonori Habuchi
  • Organizer: Annual Meeting of America Urological Association
  • Place of Presentation: San Diego, CA, USA
  • Year and Date: 2016-05-06
  • Int'l Joint Research
• [Presentation] 進行性腎癌におけるアキシチニブの効果予測を目的とした血清バイオマーカーの探索 (2015)
  • Author(s): 鈴木直子、土谷順彦、成田伸太郎、井上高光、齋藤満、秋濱晋、鶴田大、佐藤滋、羽渕友則
  • Organizer: 日本泌尿器科学会
  • Place of Presentation: 石川県金沢市
  • Year and Date: 2015-04-18 – 2015-04-21
• [Remarks] 秋田大学大学院 医学系研究科 腎泌尿器科学講座
  • URL: http://www.med.akita-u.ac.jp/~hinyoki/
• [Remarks] 秋田大学大学院医学系研究科 腎泌尿器科学
  • URL: http://www.med.akita-u.ac.jp/~hinyoki/