Abstract
The aim of this study to determine whether the aberrant N-glycosylated serum immunoglobulins (Igs) can be applied as a diagnostic marker of urothelial carcinoma (UC). Between 2009 and 2016, we randomly obtained serum available from 237 UC and also 96 prostate cancer as other cancer controls from our serum bank and also obtained—from 339 healthy volunteers (HV)—controls obtained from community-dwelling volunteers in Iwaki Health Promotion Project. A total of 32 types of N-glycan levels on Igs were determined by high-throughput N-glycomics and analyzed by multivariable discriminant analysis. We found five UC-associated aberrant N-glycans changes on Igs and also found that asialo-bisecting GlcNAc type N-glycan on Igs were significantly accumulated in UC patients. The diagnostic N-glycan Score (dNGScore) established by combination of five N-glycans on Igs discriminated UC patients from HV and prostate cancer (PC) patients with 92.8% sensitivity and 97.2% specificity. The area under the curve (AUC) for of the dNGScore was 0.969 for UC detection that was much superior to that of urine cytology (AUC, 0.707) and hematuria (AUC, 0.892). Furthermore, dNGScore can detect hematuria and urine cytology negative patients. The dNGscore based on aberrant N-glycosylation signatures of Igs were found to be promising diagnostic biomarkers of UCs.
Highlights
Urothelial carcinomas (UCs) are the eighth-most lethal cancer in men in the United States [1]
The majority of UCs originate from bladder, called UC of the bladder (UCB), and between 5% and 10% of UCs originate from the ureter or renal pelvis [2,3], which are collectively called upper urinary tract UCs (UTUCs), with a worse prognosis than that of UCB
The asialo biantennary type N-glycan (m/z 1769) on Igs was significantly downregulated in the prostate cancer (PC) group compared with the level in the UC and healthy volunteers (HV) groups (p = 0.0001)
Summary
Urothelial carcinomas (UCs) are the eighth-most lethal cancer in men in the United States [1]. Our group reported that a combination of several serum N-glycans (N-glycan score, NGScore) is a novel serum marker for UCs including UTUC that detected 93% of UC patients and is far more specific than classic urine cytology [19] We hypothesized that these serum aberrant N-glycan change is derived from serum major N-glycosylated proteins, such as immunoglobulins (Igs). 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. for clinical applications, we established a diagnostic NGScore (dNGScore) based on a combination of five N-glycans of Igs associated with detection of UCs
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