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Published in: BMC Cancer 1/2018

Open Access 01-12-2018 | Research article

Serum leucine-rich alpha-2-glycoprotein-1 with fucosylated triantennary N-glycan: a novel colorectal cancer marker

Authors: Eiji Shinozaki, Kazuhiro Tanabe, Takashi Akiyoshi, Tomohiro Tsuchida, Yuko Miyazaki, Nozomi Kojima, Masahiro Igarashi, Masashi Ueno, Mitsukuni Suenaga, Nobuyuki Mizunuma, Kensei Yamaguchi, Konosuke Nakayama, Sadayo Iijima, Toshiharu Yamaguchi

Published in: BMC Cancer | Issue 1/2018

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Abstract

Background

Carcinoembryonic antigen (CEA) and carbohydrate antigen (CA)19–9 are used in clinical practice as tumor markers to diagnose or monitor colorectal cancer (CRC) patients, However, their specificities and sensitivities are not ideal, and novel alternatives are needed. In this study, mass spectrometry was used to search for screening markers, focusing on glycan alterations of glycoproteins in the sera of CRC patients.

Methods

Glycopeptides were prepared from serum glycoproteins separated from blood samples of 80 CRC patients and 50 healthy volunteers, and their levels were measured by liquid chromatography time-of flight mass spectrometry (LC–TOF–MS).

Results

Leucine-rich alpha-2-glycoprotein-1 with fucosylated triantennary N-glycan (LRG–FTG) was identified as CRC marker after evaluating 30,000 candidate glycopeptide peaks. The average LRG–FTG level in CRC patients (1.25 ± 0.973 U/mL) was much higher than that in healthy volunteers (0.496 ± 0.433 U/mL, P < 10− 10), and its sensitivity and specificity exceeded those of CA19–9. The combination of CEA and LRG–FTG showed a complementary effect and had better sensitivity (84%), specificity (90%), and AUC (0.91 by ROC analysis) than each marker alone or any other previously reported marker. LRG–FTG alone or combined with CEA also corresponded well with patient response to treatment.

Conclusions

We identified LRG–FTG as a new CRC marker, with a sensitivity and specificity exceeding CA19–9. The combination of LRG–FTG and CEA showed much higher sensitivity and specificity than each marker alone. Further validation beyond this initial exploratory cohort is warranted.
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Metadata
Title
Serum leucine-rich alpha-2-glycoprotein-1 with fucosylated triantennary N-glycan: a novel colorectal cancer marker
Authors
Eiji Shinozaki
Kazuhiro Tanabe
Takashi Akiyoshi
Tomohiro Tsuchida
Yuko Miyazaki
Nozomi Kojima
Masahiro Igarashi
Masashi Ueno
Mitsukuni Suenaga
Nobuyuki Mizunuma
Kensei Yamaguchi
Konosuke Nakayama
Sadayo Iijima
Toshiharu Yamaguchi
Publication date
01-12-2018
Publisher
BioMed Central
Published in
BMC Cancer / Issue 1/2018
Electronic ISSN: 1471-2407
DOI
https://doi.org/10.1186/s12885-018-4252-6

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