Aberrant N-Glycosylation Profile of Serum Immunoglobulins is a Diagnostic Biomarker of Urothelial Carcinomas

2019 Fiscal Year Final Research Report

• Project/Area Number: 17K16770
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Urology
• Research Institution: Hirosaki University
• Principal Investigator: Imanishi Kengo 弘前大学, 医学研究科, 客員研究員 (10793648)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Keywords: 腎盂・尿管癌 / 糖鎖バイオマーカー / 質量解析

Outline of Final Research Achievements

Urothelial carcinomas (UCs) are the eighth-most lethal cancer in men in the United States. The standard examinations are performed, involving urine cytology, urinary tract imaging and cystoscopy, which are powerful diagnostic tools for UCs. However, Urine cytology is not reliable in patients with early stage UCs, including UTUC, and it is difficult to visualise small tumors via imaging modalities, such as ultrasound or computed tomography. Thus, more sensitive and non-invasive biomarkers, such as serum-based biomarkers, to avoid under-detection in patients at high risk of UCs is required. In the present study, we performed N-glycomics of serum Igs fractions between healthy volunteers (HVs), prostate cancer (PC) and UCs patients to identify the UC-specific aberrant N-glycosylated Igs. Furthermore, for clinical applications, we established a diagnostic NGScore (dNGScore) based on a combination of five N-glycans of Igs associated with detection of UCs.

Free Research Field

泌尿器腫瘍学

Academic Significance and Societal Importance of the Research Achievements

腎盂・尿管癌の診断において、尿細胞診は中核となる診断法の一つであるが、その感度は低く、進行度との相関関係も低いとされている。近年、CT urographyが腎盂・尿管癌診断の第一選択とされてはいるが、CISや小径腫瘤では偽陰性の危険性が高い。また、尿管鏡検査も癌の検出、確定診断に有用であるとされているが、尿管鏡下腫瘍生検の癌確定における陽性的中率は決して高いものではない。さらに約60％が発見段階で、局所進行性もしくは転移性であることが多く、予後不良の疾患であり、早期発見が極めて重要である。尿細胞診を凌駕する低侵襲な腎盂・尿管癌診断マーカーの実用化は治療効果向上につながる可能性がある。