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Somers N, Butaye E, Grossar L, Pauwels N, Geerts A, Raevens S, Lefere S, Devisscher L, Meuris L, Callewaert N, Vlierberghe HV, Verhelst X. Glycomics as prognostic biomarkers of hepatocellular carcinoma: A systematic review. Oncol Lett 2025; 29:24. [PMID: 39530005 PMCID: PMC11551839 DOI: 10.3892/ol.2024.14769] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/13/2024] [Accepted: 09/10/2024] [Indexed: 11/16/2024] Open
Abstract
Hepatocellular carcinoma (HCC) is one of the most lethal malignancies, which is associated with a low 5-year survival rate. The importance of effective disease monitoring and prognostic evaluation is undeniable. For the present study, a systematic review was performed using extensive searches in Medline, Embase, Web of Science and Scopus up to December 29, 2023. The aim of the present study was to examine whether N-glycomics could predict the risk of developing HCC in adults with chronic liver disease and, if HCC was present, predict overall survival. As a secondary outcome, the prediction capability of HCC recurrence was assessed. After deduplication, 3,904 studies were identified, of which 30 were included. Overall, the median size of the study cohort was 144 patients, with a median follow-up time of 63.6 months. Three studies explored N-glycomics in whole serum, whereas the rest focused on individual glycoproteins, with Mac-2 binding protein glycosylation isomer (M2BPGi) being the most commonly studied. Most articles investigated baseline M2BPGi values as predictors for the development of HCC and demonstrated a median area under the curve of 0.83 with a cut-off index value of 1.8. In conclusion, it was revaled that N-glycan changes exhibit added value in determining patient prognosis in terms of survival, monitoring HCC development and recurrence.
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Affiliation(s)
- Nicky Somers
- Department of Gastroenterology and Hepatology, Ghent University Hospital, 9000 Ghent, Belgium
- Hepatology Research Unit, Liver Research Center Ghent, Ghent University, 9000 Ghent, Belgium
| | - Emma Butaye
- Department of Gastroenterology and Hepatology, Ghent University Hospital, 9000 Ghent, Belgium
- Hepatology Research Unit, Liver Research Center Ghent, Ghent University, 9000 Ghent, Belgium
| | - Lorenz Grossar
- Department of Gastroenterology and Hepatology, Ghent University Hospital, 9000 Ghent, Belgium
- Hepatology Research Unit, Liver Research Center Ghent, Ghent University, 9000 Ghent, Belgium
| | - Nele Pauwels
- Knowledge Center for Health Ghent, Ghent University, Ghent University Hospital, 9000 Ghent, Belgium
| | - Anja Geerts
- Department of Gastroenterology and Hepatology, Ghent University Hospital, 9000 Ghent, Belgium
- Hepatology Research Unit, Liver Research Center Ghent, Ghent University, 9000 Ghent, Belgium
| | - Sarah Raevens
- Department of Gastroenterology and Hepatology, Ghent University Hospital, 9000 Ghent, Belgium
- Hepatology Research Unit, Liver Research Center Ghent, Ghent University, 9000 Ghent, Belgium
| | - Sander Lefere
- Department of Gastroenterology and Hepatology, Ghent University Hospital, 9000 Ghent, Belgium
- Hepatology Research Unit, Liver Research Center Ghent, Ghent University, 9000 Ghent, Belgium
- Department of Basic and Applied Medical Sciences, Gut-Liver Immunopharmacy Unit, Faculty of Medicine and Health Sciences, Ghent University, 9000 Ghent, Belgium
| | - Lindsey Devisscher
- Hepatology Research Unit, Liver Research Center Ghent, Ghent University, 9000 Ghent, Belgium
- Department of Basic and Applied Medical Sciences, Gut-Liver Immunopharmacy Unit, Faculty of Medicine and Health Sciences, Ghent University, 9000 Ghent, Belgium
| | - Leander Meuris
- Department of Biochemistry and Microbiology, VIB-UGent Center for Biotechnology, 9000 Ghent, Belgium
- Department of Biochemistry and Microbiology, Ghent University, 9000 Ghent, Belgium
| | - Nico Callewaert
- Department of Biochemistry and Microbiology, VIB-UGent Center for Biotechnology, 9000 Ghent, Belgium
- Department of Biochemistry and Microbiology, Ghent University, 9000 Ghent, Belgium
| | - Hans Van Vlierberghe
- Department of Gastroenterology and Hepatology, Ghent University Hospital, 9000 Ghent, Belgium
- Hepatology Research Unit, Liver Research Center Ghent, Ghent University, 9000 Ghent, Belgium
| | - Xavier Verhelst
- Department of Gastroenterology and Hepatology, Ghent University Hospital, 9000 Ghent, Belgium
- Hepatology Research Unit, Liver Research Center Ghent, Ghent University, 9000 Ghent, Belgium
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Liu X, Zhang W, Ma B, Lv C, Sun M, Shang Q. The value of serum Mac-2 binding protein glycosylation isomer in the diagnosis of liver fibrosis: a systematic review and meta-analysis. Front Physiol 2024; 15:1382293. [PMID: 39558944 PMCID: PMC11570841 DOI: 10.3389/fphys.2024.1382293] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/16/2024] [Accepted: 09/30/2024] [Indexed: 11/20/2024] Open
Abstract
Background The early detection and intervention of liver fibrosis (LF) in patients with chronic liver disease is critical to their management. The accuracy of serum Mac-2 binding protein glycosylation isomer (M2BPGi) in the diagnosis of LF remains controversial. This study aimed to comprehensively assess the value of serum M2BPGi in diagnosing LF. Methods The PubMed, Embase, MEDLINE, Web of Science, and Cochrane Library databases were searched. The effect values were combined using a random-effects model. Meta-regression and subgroup analysis were used to explore the sources of heterogeneity. In addition, publication bias assessment and sensitivity analysis were conducted. Results This study includes 12 studies with 2,416 patients. The pooled sensitivity, specificity, and AUROC of M2BPGi in the diagnosis of significant fibrosis (≥F2) were 0.65 (95% CI: 0.57-0.71), 0.79 (95% CI: 0.72-0.84), and 0.78 (95% CI: 0.74-0.81), respectively, while those for predicting extensive fibrosis (≥F3) were 0.76 (95% CI: 0.71-0.80), 0.75 (95% CI: 0.68-0.81), and 0.81 (95% CI: 0.77-0.84). Sensitivity analysis indicated stable results in this study. The disease type, cut-off values, study country, average age, and male proportion were the sources of heterogeneity in diagnosing significant fibrosis of M2BPGi (p < 0.05). Sample size, disease type, study country, publication year, cut-off values, average age, and male proportion were important sources of heterogeneity in diagnosing extensive fibrosis (p < 0.05). Conclusion Serum M2BPGi has good diagnostic performance for significant fibrosis and extensive fibrosis in patients with chronic hepatitis B (CHB), chronic hepatitis C (CHC), or nonalcoholic fatty liver disease (NAFLD) and is an effective, non-invasive, and convenient marker. Systematic Review Registration https://inplasy.com/inplasy-2023-10-0086/.
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Affiliation(s)
- Xinyu Liu
- College of First Clinical Medicine, Shandong University of Traditional Chinese Medicine, Jinan, Shandong, China
| | - Wei Zhang
- Department of Liver Disease, The 960th Hospital of the PLA Joint Logistics Support Force, Jinan, China
| | - Baofeng Ma
- The third department of encephalopathy, Jinan Integrated Traditional Chinese and Western Medicine Hospital, Jinan, China
| | - Chunlei Lv
- Diagnosis and Treatment Center for Liver Diseases, Tai’an 88 Hospital, Taian, China
| | - Mimi Sun
- Diagnosis and Treatment Center for Liver Diseases, Tai’an 88 Hospital, Taian, China
| | - Qinghua Shang
- Department of Liver Disease, The 960th Hospital of the PLA Joint Logistics Support Force, Jinan, China
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Takakusagi S, Sato K, Marubashi K, Kizawa K, Kosone T, Kakizaki S, Takagi H, Uraoka T. Impact of M2BPGi on the Hepatocarcinogenesis after the Combination Therapy with Daclatasvir and Asunaprevir for Hepatitis C. Biomedicines 2021; 9:660. [PMID: 34201309 PMCID: PMC8227298 DOI: 10.3390/biomedicines9060660] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/20/2021] [Revised: 06/03/2021] [Accepted: 06/03/2021] [Indexed: 01/08/2023] Open
Abstract
The clinical significance of mac-2 binding protein glycosylation isomer (M2BPGi) levels based on virological responses due to antiviral therapy has not been fully evaluated. We compared the change before and 24 weeks after the therapy with daclatasvir and asunaprevir (DCV+ASV) of M2BPGi levels with those of other fibrosis markers in 73 chronic hepatitis C cases. Moreover, we examined the association between M2BPGi levels and hepatocarcinogenesis in sustained virological response (SVR) and non-SVR cases. M2BPGi levels were significantly improved at post-treatment week 24 (PTW24) in SVR but not non-SVR cases, whereas the changes of other fibrosis markers showed the same tendency in both SVR and non-SVR cases. M2BPGi levels were well correlated with other fibrosis markers at baseline but not PTW24. The incidence of hepatocellular carcinoma (HCC) was significantly associated with M2BPGi levels at PTW24. The achievement of SVR significantly affected the improvement of M2BPGi levels that best reflected the effect of direct-acting antivirals among the fibrosis markers. Furthermore, M2BPGi levels at PTW24 were also associated with the incidence of HCC in only SVR cases. However, the rapid decrease of M2BPGi levels might reflect the amelioration of liver inflammation rather than the improvement of liver fibrosis, which should be further elucidated.
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Affiliation(s)
- Satoshi Takakusagi
- Department of Gastroenterology and Hepatology, Kusunoki Hospital, Fujioka, Gunma 375-0024, Japan; (S.T.); (K.M.); (K.K.); (T.K.); (H.T.)
| | - Ken Sato
- Department of Gastroenterology and Hepatology, Gunma University Graduate School of Medicine, Maebashi, Gunma 371-8511, Japan; (S.K.); (T.U.)
| | - Kyoko Marubashi
- Department of Gastroenterology and Hepatology, Kusunoki Hospital, Fujioka, Gunma 375-0024, Japan; (S.T.); (K.M.); (K.K.); (T.K.); (H.T.)
| | - Kazuko Kizawa
- Department of Gastroenterology and Hepatology, Kusunoki Hospital, Fujioka, Gunma 375-0024, Japan; (S.T.); (K.M.); (K.K.); (T.K.); (H.T.)
| | - Takashi Kosone
- Department of Gastroenterology and Hepatology, Kusunoki Hospital, Fujioka, Gunma 375-0024, Japan; (S.T.); (K.M.); (K.K.); (T.K.); (H.T.)
| | - Satoru Kakizaki
- Department of Gastroenterology and Hepatology, Gunma University Graduate School of Medicine, Maebashi, Gunma 371-8511, Japan; (S.K.); (T.U.)
| | - Hitoshi Takagi
- Department of Gastroenterology and Hepatology, Kusunoki Hospital, Fujioka, Gunma 375-0024, Japan; (S.T.); (K.M.); (K.K.); (T.K.); (H.T.)
| | - Toshio Uraoka
- Department of Gastroenterology and Hepatology, Gunma University Graduate School of Medicine, Maebashi, Gunma 371-8511, Japan; (S.K.); (T.U.)
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Tamaki N, Kurosaki M, Loomba R, Izumi N. Clinical Utility of Mac-2 Binding Protein Glycosylation Isomer in Chronic Liver Diseases. Ann Lab Med 2020; 41:16-24. [PMID: 32829576 PMCID: PMC7443525 DOI: 10.3343/alm.2021.41.1.16] [Citation(s) in RCA: 31] [Impact Index Per Article: 6.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/21/2020] [Revised: 06/15/2020] [Accepted: 07/29/2020] [Indexed: 12/15/2022] Open
Abstract
An accurate evaluation of liver fibrosis is clinically important in chronic liver diseases. Mac-2 binding protein glycosylation isomer (M2BPGi) is a novel serum marker for liver fibrosis. In this review, we discuss the role of M2BPGi in diagnosing liver fibrosis in chronic hepatitis B and C, chronic hepatitis C after sustained virologic response (SVR), and nonalcoholic fatty liver disease (NAFLD). M2BPGi predicts not only liver fibrosis but also the hepatocellular carcinoma (HCC) development and prognosis in patients with chronic hepatitis B and C, chronic hepatitis C after SVR, NAFLD, and other chronic liver diseases. M2BPGi can also be used to evaluate liver function and prognosis in patients with cirrhosis. M2BPGi levels vary depending on the etiology and the presence or absence of treatment. Therefore, the threshold of M2BPGi for diagnosing liver fibrosis and predicting HCC development has to be adjusted according to the background and treatment status.
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Affiliation(s)
- Nobuharu Tamaki
- Department of Gastroenterology and Hepatology, Musashino Red Cross Hospital, Tokyo, Japan.,NAFLD Research Center, Division of Medicine, University of California, San Diego, La Jolla, California, USA
| | - Masayuki Kurosaki
- Department of Gastroenterology and Hepatology, Musashino Red Cross Hospital, Tokyo, Japan
| | - Rohit Loomba
- NAFLD Research Center, Division of Medicine, University of California, San Diego, La Jolla, California, USA
| | - Namiki Izumi
- Department of Gastroenterology and Hepatology, Musashino Red Cross Hospital, Tokyo, Japan
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Pham TTT, Ho DT, Nguyen T. Usefulness of Mac-2 binding protein glycosylation isomer in non-invasive probing liver disease in the Vietnamese population. World J Hepatol 2020; 12:220-229. [PMID: 32547689 PMCID: PMC7280857 DOI: 10.4254/wjh.v12.i5.220] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/01/2020] [Revised: 03/30/2020] [Accepted: 04/07/2020] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Early diagnosis is critical for successful intervention before liver disease progresses to cirrhosis and hepatocellular carcinoma. AIM To examine a novel biomarker for probing early liver disease quickly using an automated immunology system. METHODS This was a cross-sectional study. 140 patients at various stages of liver disease were randomly selected. The cohort consisted of patients who were treatment naïve and currently undergoing therapy. We included patients with diverse liver disease etiologies. Mac-2 binding protein glycosylation isomer (M2BPGi) levels in addition to different clinical parameters, co-morbidities and transient elastography results were collected and compared. RESULTS M2BPGi levels were significantly correlated with transient elastography for liver fibrosis staging across all disease etiologies. Statistically significant differences were observed in patients with F0-1; F2 and > F3 liver fibrosis. Further examination showed that M2BPGi levels were two-fold higher in F4 than F3 hepatitis C (HCV) patients. M2BPGi was observed to be etiology-specific and HCV patients had higher mean M2BPGi levels. We also observed significant correlations with aspartate aminotransferase to platelet ratio index and fibrosis-4 index as well as HBV DNA levels. Mean M2BPGi levels for HBV patients with a viral load lower than 2000 IU/mL was 1.75-fold lower than those with a viral load greater than 2000 IU/mL. CONCLUSION M2BPGi was observed to be a good indicator of early liver disease in patients with different etiologies. Our results provide reference cut-offs for different causes of liver disease and demonstrated the utility of this marker for early disease monitoring. This is useful for remote regions in developing countries.
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Affiliation(s)
| | - Dat Tan Ho
- MEDIC Medical Center, Ho Chi Minh 72517, Vietnam
| | - Toan Nguyen
- MEDIC Medical Center, Ho Chi Minh 72517, Vietnam
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