Valentina Peta1, Jianhui Zhu2, David M Lubman2, Samuel Huguet3, Francoise Imbert-Bismutd4, Gérard Bolbach5, Gilles Clodic6, Lucrèce Matheron6, Yen Ngo7, Pais Raluca8, Chantal Housset9, Keyvan Rezai3, Thierry Poynard10. 1. BioPredictive, 75007 Paris, France; Sorbonne Université, Inserm, Centre de Recherche Saint-Antoine (CRSA), 75012 Paris, France. 2. Department of Surgery, University of Michigan Medical Center, Ann Arbor, MI 48019, USA. 3. Radiopharmacology Department, Institut Curie, 92210 Saint Cloud, France. 4. Assistance Publique-Hôpitaux de Paris (AP-HP), Groupe Hospitalier Pitié-Salpêtrière (GHPS), 75013 Paris, France. 5. Sorbonne Université, Institut de Biologie Paris Seine, Plate-forme spectrométrie de masse et protéomique, 75005 Paris, France; Sorbonne Université, École normale supérieure, PSL University, CNRS, Laboratoire des Biomolécules (LBM), 75005 Paris, France. 6. Sorbonne Université, Institut de Biologie Paris Seine, Plate-forme spectrométrie de masse et protéomique, 75005 Paris, France. 7. BioPredictive, 75007 Paris, France. 8. Assistance Publique-Hôpitaux de Paris (AP-HP), Groupe Hospitalier Pitié-Salpêtrière (GHPS), 75013 Paris, France; Sorbonne Université, Inserm, Centre de Recherche Saint-Antoine (CRSA), 75012 Paris, France. 9. Sorbonne Université, Inserm, Centre de Recherche Saint-Antoine (CRSA), 75012 Paris, France. 10. Assistance Publique-Hôpitaux de Paris (AP-HP), Groupe Hospitalier Pitié-Salpêtrière (GHPS), 75013 Paris, France; Sorbonne Université, Inserm, Centre de Recherche Saint-Antoine (CRSA), 75012 Paris, France. Electronic address: thierry@poynard.com.
Abstract
BACKGROUND: Haptoglobin bifucosylated tetra-antennary glycan have been identified in patients with early stage hepatocellular carcinoma, but its specificity according to the presence or not of cirrhosis has never been assessed. The aims of this study were to determine if haptoglobin bifucosylated tetra-antennary glycan (1) could be a marker of HCC in patients without cirrhosis; (2) could increase the performance of standard alpha-fetoprotein (AFP) or recent blood tests for HCC detection, i.e., lectin-reactive alpha-fetoprotein (AFP-L3), des-gamma-carboxy prothrombin (DCP) and Liver-Cancer-Risk-test (LCR1-test). METHODS: We retrospectively selected patients, 102 with HCC (21 without cirrhosis), matched by stages with 140 controls without HCC (81 without cirrhosis). Haptoglobin fucosylation was assessed by MALDI-TOF. LCR-glycan algorithm was constructed combining components of the LCR-1 test (haptoglobin, gammaglutamyl-transpeptidase, apolipoproteinA1, alpha-2-macroglobulin) with AFP, AFP-L3, DCP and haptoglobin bifucosylated tetra-antennary glycan. RESULTS: In 102 patients without cirrhosis (21 HCC and 81 controls), the intention-to-diagnose analyses showed that haptoglobin bifucosylated tetra-antennary glycan alone had a sensitivity of 71% (15/21;95%CI 50-86), significantly better (P=0.02) than standard AFP (43%;9/21;95%CI 24-63), and a specificity of 96% (78/81;95% 90-99). The sensitivity of LCR-glycan, in patients without cirrhosis, was 86% (18/21; 95%CI 63-95) significantly better (P=0.001) than standard AFP (43%; 9/21; 95%CI 24-63), with an AUROC of 0.943 (95%CI 0.806-0.98) compared to 0.811 (95%CI 0.630-0.908) for AFP (P=0.06). CONCLUSION: Haptoglobin bifucosylated tetra-antennary glycan is associated with the presence of HCC in patients with chronic liver disease including those without cirrhosis. Its combination with existing HCC biomarkers could improve the performance of standard AFP for HCC detection.
BACKGROUND:Haptoglobin bifucosylated tetra-antennary glycan have been identified in patients with early stage hepatocellular carcinoma, but its specificity according to the presence or not of cirrhosis has never been assessed. The aims of this study were to determine if haptoglobin bifucosylated tetra-antennary glycan (1) could be a marker of HCC in patients without cirrhosis; (2) could increase the performance of standard alpha-fetoprotein (AFP) or recent blood tests for HCC detection, i.e., lectin-reactive alpha-fetoprotein (AFP-L3), des-gamma-carboxy prothrombin (DCP) and Liver-Cancer-Risk-test (LCR1-test). METHODS: We retrospectively selected patients, 102 with HCC (21 without cirrhosis), matched by stages with 140 controls without HCC (81 without cirrhosis). Haptoglobin fucosylation was assessed by MALDI-TOF. LCR-glycan algorithm was constructed combining components of the LCR-1 test (haptoglobin, gammaglutamyl-transpeptidase, apolipoproteinA1, alpha-2-macroglobulin) with AFP, AFP-L3, DCP and haptoglobin bifucosylated tetra-antennary glycan. RESULTS: In 102 patients without cirrhosis (21 HCC and 81 controls), the intention-to-diagnose analyses showed that haptoglobin bifucosylated tetra-antennary glycan alone had a sensitivity of 71% (15/21;95%CI 50-86), significantly better (P=0.02) than standard AFP (43%;9/21;95%CI 24-63), and a specificity of 96% (78/81;95% 90-99). The sensitivity of LCR-glycan, in patients without cirrhosis, was 86% (18/21; 95%CI 63-95) significantly better (P=0.001) than standard AFP (43%; 9/21; 95%CI 24-63), with an AUROC of 0.943 (95%CI 0.806-0.98) compared to 0.811 (95%CI 0.630-0.908) for AFP (P=0.06). CONCLUSION:Haptoglobin bifucosylated tetra-antennary glycan is associated with the presence of HCC in patients with chronic liver disease including those without cirrhosis. Its combination with existing HCC biomarkers could improve the performance of standard AFP for HCC detection.
Authors: M Munteanu; D Tiniakos; Q Anstee; F Charlotte; G Marchesini; E Bugianesi; M Trauner; M Romero Gomez; C Oliveira; C Day; J-F Dufour; S Bellentani; Y Ngo; S Traussnig; H Perazzo; O Deckmyn; P Bedossa; V Ratziu; T Poynard Journal: Aliment Pharmacol Ther Date: 2016-08-23 Impact factor: 8.171