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The diagnostic value of serum DSA-TRF in hepatocellular carcinoma

  • Wenqian Guan
  • Zhiyuan Gao
  • Chenjun Huang
  • Meng Fang
  • Huijuan Feng
  • Shipeng Chen
  • Mengmeng Wang
  • Jun Zhou
  • Song Hong
  • Chunfang GaoEmail author
Original Article

Abstract

TRF is a glycoprotein mainly secreted by hepatocytes, The aim of this study was to explore the diagnostic value of aberrant glycosylated serum transferrin (TRF) especially containing multi-antennary glycans in hepatocellular carcinoma (HCC).A total of 581 subjects including HCC patients, liver cirrhosis (LC) patients, chronic hepatitis (CHB) patients and healthy controls (HC) were recruited. All the subjects were randomly assigned to training group (n = 411) and validation group (n = 170). We firstly analyzed the serum protein N-glycome profiling of HCC, LC, and HC by DNA sequencer–assisted fluorophore-assisted carbohydrate electrophoresis (DSA-FACE) technology. We established a lectin-antibody sandwich ELISA (Lectin-ELISA) method to detect multi-antennary glycans-contained TRF (DSA-TRF) in serum, in which Datura stramonium Agglutinin (DSA) was used for specific recognition. Levels of serum DSA-TRF and TRF were analyzed respectively. The diagnostic efficacies of DSA-TRF and TRF of differentiating HCC patients from CHB, LC patients and HC within the training group were evaluated using receiver operating characteristic (ROC) curve and tested in the validation group.The result found that in training group, serum TRF and DSA-TRF levels differed significantly between HCC (1.86 ± 0.50, g/L, 0.285 ± 0.06), CHB + LC (2.39 ± 0.74, g/L, 0.189 ± 0.07) and HC (1.92 ± 0.69, g/L, 0.249 ± 0.09) (HCC vs. CHB + LC, P < 0.001; HCC vs. HC, P < 0.001; CHB + LC vs. HC, P < 0.001). The area under the ROC curve (AUC) of DSA-TRF was significantly superior to AFP (0.880, 95%CI: 0.834–0.925 vs. 0.776, 95%CI: 0.725–0.827, P = 0.003) in differentiating HCC from CHB + LC. The AUC of diagnostic model GlycoTRF1 (0.981, 95%CI: 0.969–0.993) was higher than DSA-TRF and AFP alone (P<0.001) in differentiating HCC from CHB + LC, which was verified in validation group.The results indicated that the serum DSA-TRF might serve as a potential glycan biomarker for distinguishing HCC from CHB and LC.

Keywords

Transferrin Hepatocellular carcinoma Glycan biomarker 

Notes

Acknowledgements

This study was funded by the National Science and Technology Major Project of China (2018ZX10302205-003) and the Science and Technology Commission of Shanghai Municipality(17JC1404500, 17411960500, 15JC1404100).

Compliance with ethical standards

Conflict of interest

The authors declare that there are no conflicts of interest.

Ethical approval

This article does not contain any studies with human participants or animals performed by any of the authors.

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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2020

Authors and Affiliations

  1. 1.Department of Laboratory MedicineShanghai Eastern Hepatobiliary Surgery HospitalShanghaiPeople’s Republic of China
  2. 2.Clinical Medical CollegeFujian Medical UniversityFuzhouPeople’s Republic of China
  3. 3.Department of Emergency Medicine, Jinling HospitalMedical School of Nanjing UniversityNanjingPeople’s Republic of China

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