Development of predictive biomarker for kidney transplant disorder by comprehensive structural analysis on serum glycan

• Project/Area Number: 15K15579
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Urology
• Research Institution: Hirosaki University
• Principal Investigator: Ohyama Chikara 弘前大学, 医学研究科, 教授 (80282135)
• Co-Investigator(Kenkyū-buntansha): 畠山 真吾 弘前大学, 医学部附属病院, 講師 (10400136) ; 盛 和行 弘前大学, 医学研究科, 助教 (40266903) ; 米山 徹 弘前大学, 医学研究科, 助教 (50587649) ; 古家 琢也 弘前大学, 医学研究科, 准教授 (60321965) ; 飛澤 悠葵 弘前大学, 医学研究科, 助教 (70623768) ; 佐藤 滋 秋田大学, 医学部, 教授 (80187195)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥3,510,000 (Direct Cost: ¥2,700,000、Indirect Cost: ¥810,000); Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2016: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2015: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000)
• Keywords: 腎移植 / 抗体関連拒否 / 糖鎖 / 抗体関連拒絶 / 質量解析

Outline of Final Research Achievements

We determined if the serum N-glycan profile can be used as a diagnostic marker of antibody-mediated rejection (ABMR) in living donor kidney transplant (LKTx) recipients. Glycoblotting, combined with mass spectrometry, was used to retrospectively examine N-glycan levels in the postoperative sera of 197 LKTx recipients of whom 16 recipients had ABMR with or without T-cell-mediated rejection (TCMR), 40 recipients had TCMR, and 141 recipients had no adverse events. The N-glycan score was calculated by multiplying the level of candidate objective variables by objective function values. The N-glycan score discriminated ABMR with 81.25% sensitivity, 87.85% specificity, and an area under the curve (AUC) of 0.892 that was far superior to that of preformed donor-specific antibody status (AUC, 0.761). Recipients with N-glycan-positive scores >0.8770 had significantly shorter ABMR survival than that of recipients with N-glycan-negative scores.

Research Products

• [Journal Article] Serum Aberrant N-Glycan Profile as a Marker Associated with Early Antibody-Mediated Rejection in Patients Receiving a Living Donor Kidney Transplant (2017)
  • Author(s): Noro D., Yoneyama T., Hatakeyama S., Tobisawa Y., Mori K., Hashimoto Y., Koie T., Tanaka M., Nishimura S-I., Sasaki H., Saito M., Harada H., Chikaraishi T., Ishida H., Tanabe K., Satoh S., Ohyama C.
  • Journal Title: Int. J. Mol. Sci. Volume: 18 Issue: 8 Pages: 1731-1731
  • DOI: 10.3390/ijms18081731
  • Peer Reviewed
• [Journal Article] Presence of transient hydronephrosis immediately after surgery has a limited influence on renal function 1?year after ileal neobladder construction (2017)
  • Author(s): Narita Takuma、Hatakeyama Shingo、Koie Takuya、Hosogoe Shogo、Matsumoto Teppei、Soma Osamu、Yamamoto Hayato、Yoneyama Tohru、Tobisawa Yuki、Yoneyama Takahiro、Hashimoto Yasuhiro、Ohyama Chikara
  • Journal Title: BMC Urology Volume: 17 Issue: 1 Pages: 72-79
  • DOI: 10.1186/s12894-017-0263-x
  • NAID: 120006583357
  • Peer Reviewed
• [Journal Article] Incidental prostate cancer in patients with muscle-invasive bladder cancer who underwent radical cystoprostatectomy (2017)
  • Author(s): Tanaka Toshikazu、Koie Takuya、Ohyama Chikara、Hashimoto Yasuhiro、Imai Atsushi、Tobisawa Yuki、Hatakeyama Shingo、Yamamoto Hayato、Yoneyama Tohru、Horiguchi Hirotaka、Kodama Hirotake、Yoneyama Takahiro
  • Journal Title: Japanase Journal of Clinical Oncology Volume: 47 Issue: 11 Pages: 1078-1082
  • DOI: 10.1093/jjco/hyx119
  • Peer Reviewed
• [Journal Article] Preoperative chronic kidney disease predicts poor oncological outcomes after radical cystectomy in patients with muscle-invasive bladder cancer. (2017)
  • Author(s): Hamano I, Hatakeyama S, Iwamurau H, Fujita N, Fukushi K, Narita T, Hagiwara K, Kusaka A, Hosogoe S, Yamamoto H, Tobisawa Y, Yoneyama T, Yoneyama T, Hashimoto Y, Koie T, Ito H, Yoshikawa K, Kawaguchi T, Ohyama C
  • Journal Title: Oncotarget Volume: 8 Issue: 37 Pages: 61404-61414
  • DOI: 10.18632/oncotarget.18248
  • NAID: 120006583349
  • Peer Reviewed
• [Journal Article] Risk-stratified surveillance and cost effectiveness of follow-up after radical cystectomy in patients with muscle-invasive bladder cancer. (2017)
  • Author(s): Kusaka A, Hatakeyama S, Hosogoe S, Hamano I, Iwamura H, Fujita N, Fukushi K, Narita T, Hagiwara K, Yamamoto H, Tobisawa Y, Yoneyama T, Yoneyama T, Hashimoto Y, Koie T, Ito H, Yoshikawa K, Kawaguchi T, Ohyama C
  • Journal Title: Oncotarget Volume: 8 Issue: 39 Pages: 65492-65505
  • DOI: 10.18632/oncotarget.19043
  • NAID: 120006583350
  • Peer Reviewed
• [Journal Article] Preoperative chronic kidney disease predicts poor oncological outcomes after radical nephroureterectomy in patients with upper urinary tract urothelial carcinoma. (2017)
  • Author(s): Kodama H, Hatakeyama S, Fujita N, Iwamura H, Anan G, Fukushi K, Narita T, Tanaka T, Kubota Y, Horiguchi H, Momota M, Kido K, Matsumoto T, Soma O, Hamano I, Yamamoto H, Tobisawa Y, Yoneyama T, Yoneyama T, Hashimoto Y, Koie T, Ito H, Yoshikawa K, Sasaki A, Kawaguchi T, Sato M, Ohyama C
  • Journal Title: Oncotarget. Volume: 8 Issue: 47 Pages: 83183-83194
  • DOI: 10.18632/oncotarget.20554
  • NAID: 120006583351
  • Peer Reviewed
• [Journal Article] Aberrant N-Glycosylation Profile of Serum Immunoglobulins is a Diagnostic Biomarker of Urothelial Carcinomas (2017)
  • Author(s): Tanaka Toshikazu、Yoneyama Tohru、Noro Daisuke、Imanishi Kengo、Kojima Yuta、Hatakeyama Shingo、Tobisawa Yuki、Mori Kazuyuki、Yamamoto Hayato、Imai Atsushi、Yoneyama Takahiro、Hashimoto Yasuhiro、Koie Takuya、Tanaka Masakazu、Nishimura Shin-Ichiro、Kurauchi Shizuka、Takahashi Ippei、Ohyama Chikara
  • Journal Title: Int J Mol Sci. Volume: 18 Issue: 12 Pages: 2632-2632
  • DOI: 10.3390/ijms18122632
  • Peer Reviewed / Open Access
• [Journal Article] Slow Progression of Aortic Calcification Is a Potential Benefit of Pre-emptive Kidney Transplantation. (2017)
  • Author(s): Mursawa H, Hatakeyama S, Yamamoto H, Tanaka Y, Soma O, Matsumoto T, Yoneyama T, Hashimoto Y, Koie T, Fujita T, Murakami R, Saitoh H, Suzuki T, Narumi S, Ohyama C
  • Journal Title: Transplant Proc. Volume: 50 Issue: 1 Pages: 145-149
  • DOI: 10.1016/j.transproceed.2017.12.011
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Clinical implications of serum N-glycan profiling as a diagnostic and prognostic biomarker in germ-cell tumors. (2017)
  • Author(s): Narita T, Hatakeyama S, Yoneyama T, Narita S, Yamashita S, Mitsuzuka K, Sakurai T, Kawamura S, Tochigi T, Takahashi I, Nakaji S, Tobisawa Y, Yamamoto H, Koie T, Tsuchiya N, Habuchi T, Arai Y, Ohyama C.
  • Journal Title: Cancer Med. Volume: 6 Issue: 4 Pages: 739-748
  • DOI: 10.1002/cam4.1035
  • NAID: 120006583347
  • Peer Reviewed / Open Access
• [Journal Article] Safety and Effectiveness of Marginal Donor in Living Kidney Transplantation. (2016)
  • Author(s): Oikawa M, Hatakeyama S, Narita T, Yamamoto H, Hosogoe S, Imai A, Yoneyama T, Hashimoto Y, Koie T, Fujita T, Murakami R, Saitoh H, Funyu T, Narumi S, Ohyama C.
  • Journal Title: Transplant Proc. Volume: 48 Issue: 3 Pages: 701-705
  • DOI: 10.1016/j.transproceed.2015.09.067
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Characterization of clinical and genetic risk factors associated with dyslipidemia after kidney transplantation. (2015)
  • Author(s): Numakura K, Kagaya H, Yamamoto R, Komine N, Saito M, Hiroshi T, Akihama S, Inoue T, Narita S, Tsuchiya N, Habuchi T, Niioka T, Miura M, Satoh S.
  • Journal Title: Dis Markers Volume: 2015 Pages: 179434-179434
  • DOI: 10.1155/2015/179434
  • Peer Reviewed / Open Access
• [Journal Article] Pharmacokinetic and CYP3A5 pharmacogenetic differences between once- and twice-daily tacrolimus from the first dosing day to 1 year after renal transplantation. (2015)
  • Author(s): Satoh S, Niioka T, Kagaya H, Numakura K, Inoue T, Saito M, Komine N, Narita S, Tsuchiya N, Habuchi T, Miura M.
  • Journal Title: Pharmacogenomics. Volume: 15(11) Issue: 11 Pages: 1495-506
  • DOI: 10.2217/pgs.14.98
  • Peer Reviewed / Open Access
• [Presentation] 網羅的血清糖鎖分析による生体腎移植後拒絶反応予測マーカーの開発． (2018)
  • Author(s): 畠山真吾，米山 徹，齋藤 満，佐藤 滋，原田 浩，石田英樹，田邉一成，佐々木秀郎，力石辰也，大山 力
  • Organizer: 第27回泌尿器科分子・細胞研究会
• [Presentation] 多発性嚢胞腎症例における腎移植後の固有腎容積の追跡． (2018)
  • Author(s): 村上礼一，奈川大輝，中田真道，成田育代，藤田 雄，島田美智子，中村典雄，富田泰史，畠山真吾，米山高弘，橋本安弘，古家琢也，大山 力
  • Organizer: 第51回日本臨床腎移植学会
• [Presentation] 糸球体基底膜厚と術後ドナー腎機能についての検討 (2018)
  • Author(s): 畠山真吾，橋本安弘，成田育代，島田美智子，藤田 雄，村上礼一，米山高弘，古家琢也，鳴海俊治，大山 力
  • Organizer: 第51回日本臨床腎移植学会
• [Presentation] LABScreen モニタリングを行ったDQ高値の1例 (2018)
  • Author(s): 盛 和行，樺澤憲治，米山美穂子，村上礼一，藤田 雄，得居範子，山本勇人，今井 篤，畠山真吾，米山高弘，橋本安弘，古家琢也，山谷金光，齋藤久夫，鈴木唯司，大山 力
  • Organizer: 第51回日本臨床腎移植学会
• [Presentation] Significance of serum N-glycan profiling as a diagnostic biomarker in urothelial carcinoma. (2017)
  • Author(s): Oikawa M, Hatakeyama S, Yoneyma, T Tobisawa Y, Narita T, Yamamoto H, Hashimoto Y, Koie T, Narita S, Tsuchiya N, Habuchi T, Takahashi I, Nakaji S, Ohyama C
  • Organizer: 第32回欧州泌尿器科学会（EAU）
  • Place of Presentation: ロンドン（イングランド）
  • Year and Date: 2017-03-24
  • Int'l Joint Research
• [Presentation] Clinical implications of serum N-glycanprofiling as a diagnostic and prognostic biomarker in germ-cell tumors (2017)
  • Author(s): Narita T, Hatakeyama S, Yoneyama T, Narita S, Yamashita S, Mitsuzuka K, Sakurai T, Kawamura S, Tochigi T, Takahashi I,Nakaji S, Tobisawa Y, Yamamoto H, Koie T,Tsuchiya N, Habuchi T, Arai Y, Ohyama C
  • Organizer: 第112回米国泌尿器科学会議(AUA 2017)
  • Int'l Joint Research
• [Presentation] Serum N-glycomics predicts in patients who developed castration resistant prostate cancer． (2017)
  • Author(s): Yoneyama T, Tobisawa Y, Hatakeyama S, Mori K, Hashimoto Y, Koie T, Ohyama C
  • Organizer: 第112回米国泌尿器科学会議(AUA 2017)
  • Int'l Joint Research
• [Presentation] Significance of serum N-glycan profiling as a diagnostic biomarker in urothelial carcinoma． (2017)
  • Author(s): Oikawa M, Hatakeyama S, Yoneyma T, Tobisawa Y, Narita T, Yamamoto H, Hashimoto Y, Koie T, Narita S, Tsuchiya N, Habuchi T, Takahashi I, Nakaji S, Ohyama C
  • Organizer: 第112回米国泌尿器科学会議(AUA 2017)
  • Int'l Joint Research
• [Presentation] Serum sialyl hybrid typed N-glycan levels predicts early ABMR in living donor kidney transplant patients． (2017)
  • Author(s): Noro D, Yoneyama T, Hatakeyama S, Tobisawa Y, Mori K, Hashimoto Y, Koie T, Tanaka M, Nishimura S, Sasaki H, Saito M, Harada H, Chikaraishi T, Ishida H, Tanabe K, Satoh S, Ohyama C
  • Organizer: 第112回米国泌尿器科学会議(AUA 2017)
  • Int'l Joint Research
• [Presentation] Serum core fucosylated N-glycan carrying immunoglobrin is a diagnostic and pre-operative prognostic marker of upper tract urothelial carcinoma (UTUC) (2017)
  • Author(s): Tanaka T, Tobisawa Y, Hatakeyama S, Mori K, Hashimoto Y, Koie T, Ohyama C, Yoneyama
  • Organizer: 第112回米国泌尿器科学会議(AUA 2017)
  • Int'l Joint Research
• [Presentation] 血清N-結合型糖鎖の網羅的質量解析による精巣腫瘍の診断・予後マーカーの検索． (2017)
  • Author(s): 成田拓磨、畠山真吾、米山 徹、成田伸太郎、山下慎一、櫻井俊彦、飛澤悠葵、古家琢也、土谷順彦、羽渕友則、荒井陽一、大山 力
  • Organizer: 第105回日本泌尿器科学会総会
• [Presentation] 尿路上皮癌症例における新規バイオマーカーとしての血清N-glycan の網羅的質量解析． (2017)
  • Author(s): 及川真亮、畠山真吾、成田拓磨、今井 篤、米山高弘、米山 徹、橋本安弘、古家琢也、大山 力
  • Organizer: 第105回日本泌尿器科学会総会
• [Presentation] 生体腎移植ドナーガイドラインに基づいたマージナルドナーについての検討 (2017)
  • Author(s): 畠山真吾、米山高弘、城戸宏一、百田匡毅、小玉寛健、今井 篤、橋本安弘、松本哲平、濱野逸人、大山 力
  • Organizer: 第62回日本透析医学会学術集会・総会
• [Presentation] 血清N-グライコミクスによるCRPCの予測． (2017)
  • Author(s): 米山 徹
  • Organizer: 第8回Urological Expert Forum
• [Presentation] 腎移植患者における血清N型糖鎖の変化についての検討． (2017)
  • Author(s): 畠山真吾，米山 徹，野呂大輔，佐藤 滋，力石辰也，石田英樹，田邉一成，原田 浩，大山 力
  • Organizer: 第53回日本移植学会総会
• [Presentation] 血清N結合型糖鎖プロファイルによる抗体関連性拒絶の予測． (2017)
  • Author(s): 米山 徹，野呂大輔，佐々木秀郎，齋藤 満，原田 浩，力石辰也，石田英樹，田邉一成，佐藤 滋，大山 力
  • Organizer: 第53回日本移植学会総会
• [Presentation] 腹腔鏡下生体腎移植ドナー腎採取術が術後腎機能に与える影響についての検討． (2017)
  • Author(s): 及川真亮，畠山真吾，山本勇人，今井 篤，米山高弘，橋本安弘，古家琢也，大山 力
  • Organizer: 第31回日本泌尿器内視鏡学会総会
• [Presentation] Serum N-Glycan profiling predict antibody mediated rejection in patients undergoing living kidney transplantation． (2016)
  • Author(s): Noro D, Yoneyama T, Tobisawa Y, Hatakeyama S, Saito M, Hashimoto Y, Koie T, Sato S, Ohyama C
  • Organizer: 第110回米国泌尿器科学会(AUA 2016)
  • Place of Presentation: サンディエゴ（アメリカ合衆国）
  • Year and Date: 2016-05-06
  • Int'l Joint Research
• [Presentation] 当科における先行的腎移植の臨床的検討． (2016)
  • Author(s): 田中壽和，畠山真吾、相馬 理、松本哲平、日下 歩、細越正吾、濱野逸人、今井 篤、米山高弘、橋本安弘、古家琢也、大山 力
  • Organizer: 第104回日本泌尿器科学会総会
  • Place of Presentation: 仙台国際センター（宮城県・仙台市）
  • Year and Date: 2016-04-23
• [Presentation] Serum N-Glycan profiling predict antibody mediated rejection in patients undergoing living kidney transplantation (2016)
  • Author(s): Noro D, Yoneyama T, Tobisawa Y , Hatakeyama S, Saito M, Hashimoto Y, Koie T, Sato T, Ohyama C
  • Organizer: Transplantation Science Symposium (TSS) Asian Regional Meeting 2016
  • Place of Presentation: KFC Hall (東京都・墨田区）
  • Year and Date: 2016-04-08
  • Int'l Joint Research
• [Presentation] Progression of aortic calcification is indolent in patients with preemptive kidney transplantation． (2016)
  • Author(s): Hatakeyama S, Fujita T, Murakami R, Yoneyama T, Hashimoto Y, Koie T, Saitoh H, Funyu T， Narumi S, Ohyama C
  • Organizer: Transplantation Science Symposium (TSS) Asian Regional Meeting 2016
  • Place of Presentation: KFC Hall (東京都・墨田区）
  • Year and Date: 2016-04-08
  • Int'l Joint Research
• [Presentation] Serum N-Glycan profiling predict antibody mediated rejection in (2016)
  • Author(s): Daisuke Noro1, T Yoneyama2, Y Tobisawa 1, S Hatakeyama 1, M Saito3, Y Hashimoto 2, T Koie 1, S Sato 3, C Ohyama 1
  • Organizer: 欧州泌尿器科会議
  • Place of Presentation: (ミュンヘン)ICM-Internationales Congress Center
  • Year and Date: 2016-03-11
  • Int'l Joint Research