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Serum core fucosylated N-glycan carrying immunoglobrin is a diagnostic and pre-operative prognostic marker of upper tract urothelial carcinoma

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Sources of Funding: none

Introduction

Although hematuria and urine cytology is a powerful indicator for diagnosis of upper tract urothelial carcinoma (UTUC), there is a need to identify more powerful predictive biomarkers of UTUC to improve diagnostic accuracy. Prognostic biomarkers were also required to decide on therapeutic strategy of UTUC. The use of N-glycans of immunoglobrins (Igs) as a biomarkers of UTUC has not yet been tested. In the present study, we performed serum N-glycomics between healthy volunteer (HLT) and UTUC patients and evaluated its potential as a diagnostic and prognostic serum-based biomarkers of UTUC.

Methods

N-glycomics in Igs fraction were performed in randomly selected 78 HLT and 73 UTUC (preoperative serum, n=52 and post-operative serum, n=21, respectively) patients. The putative structure of N-glycans was analyzed by MALDI-TOF-MS analysis. To confirm the result of N-glycomics of Igs, We performed lectin-array analysis utilizing recombinant lectin-array chip and evanescent fluorescence scanner.

Results

N-glycomics of Igs reveled that preoperative serum core fucosylated biantennary (m/z 1590, 2073, and 2524) and core fucosylated bisecting (m/z 1647, 1793, 2955 and 2727) N-glycans of Igs levels in UTUC patients was significantly higher in HLT group. Receiver-operating characteristic area under the curve (AUC) for prediction of UTUC in significant core fucoslyalted N-glycans was 0.7290-0.8728 in contrast to hematuria positive status (AUC 0.8627) and urine cytology class ?IV (AUC 0.7745), respectively. In post-operative serum analysis, we found that the level of serum core fucosylated N-glycans in cancer death group was tend to higher than that of surviving group. Furthermore, lectin-array analysis revealed that fucoslyted IgG (Fuc-IgG) level of UTUC was tend to higher than HLT. In post-operative serum analysis, we also found serum fuc-IgG levels in cancer death group was significantly higher than that of surviving group.

Conclusions

The serum core fucosylated N-glycans levels and Fuc-IgG levels may be a promising diagnostic and post-operative prognostic markers of UTUC.

Funding

none

Authors
Toshikazu Tanaka
Yuki Tobisawa
Shingo Hatakeyama
Kazuyuki Mori
Yasuhiro Hashimoto
Takuya Koie
Chikara Ohyama
Tohru Yoneyama
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