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

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?

SUBMITTER: Shinozaki E

PROVIDER: S-EPMC5896117 | biostudies-literature | 2018 Apr

REPOSITORIES: biostudies-literature

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

Shinozaki Eiji E Tanabe Kazuhiro K Akiyoshi Takashi T Tsuchida Tomohiro T Miyazaki Yuko Y Kojima Nozomi N Igarashi Masahiro M Ueno Masashi M Suenaga Mitsukuni M Mizunuma Nobuyuki N Yamaguchi Kensei K Nakayama Konosuke K Iijima Sadayo S Yamaguchi Toshiharu T

BMC cancer 20180411 1

<h4>Background</h4>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.<h4>Methods</h4>Glycopeptides were prepared from serum glycoprot ...[more]

PMID: 29642865

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Project description:This study aimed to determine the association between umbilical cord leucine-rich alpha-2 glycoprotein (LRG) and fetal infection and investigate the underlying mechanism of LRG elevation in fetuses. We retrospectively reviewed the medical records of patients who delivered at Osaka University Hospital between 2012 and 2017 and selected those with histologically confirmed chorioamnionitis (CAM), which is a common pregnancy complication that may cause neonatal infection. The participants were divided into two groups: CAM with fetal infection (CAM-f[+] group, n = 14) and CAM without fetal infection (CAM-f[-] group, n = 31). Fetal infection was defined by the histological evidence of funisitis. We also selected 50 cases without clinical signs of CAM to serve as the control. LRG concentrations in sera obtained from the umbilical cord were unaffected by gestational age at delivery, neonatal birth weight, nor the presence of noninfectious obstetric complications (all, p > 0.05). Meanwhile, the LRG levels (median, Interquartile range [IQR]) were significantly higher in the CAM-f(+) group (10.37 [5.21-13.7] ?g/ml) than in the CAM-f(-) (3.61 [2.71-4.65] ?g/ml) or control group (3.39 [2.81-3.93] ?g/ml; p < 0.01). The area under the receiver operating characteristic (ROC) curve of LRG for recognizing fetal infection was 0.92 (optimal cutoff, 5.08 ?g/ml; sensitivity, 86%; specificity, 88%). In a mouse CAM model established by lipopolysaccharide administration, the fetal LRG protein in sera and LRG mRNA in the liver were significantly higher than those in phosphate-buffered saline (PBS)-administered control mice (p < 0.01). In vitro experiments using a fetal liver-derived cell line (WRL68) showed that the expression of LRG mRNA was significantly increased after interleukin (IL)-6, IL-1?, and tumor necrosis factor- alpha (TNF-?) stimulation (p < 0.01); the induction was considerably stronger following IL-6 and TNF-? stimulation (p < 0.01). In conclusion, LRG is an effective biomarker of fetal infection, and fetal hepatocytes stimulated with inflammatory cytokines may be the primary source of LRG production in utero.

Dataset Information

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

Publications

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

Similar Datasets

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