Browsing by Author "Fu, Siyu"

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    Assessment of TLL1 variant and risk of hepatocellular carcinoma in Latin Americans and Europeans
    (2024) Fu, Siyu; Karim, Dhamina; Prieto, Jhon; Balderramo, Domingo; Ferrer, Javier Diaz; Mattos, Angelo Z.; Arrese, Marco; Carrera, Enrique; Oliveira, Jeffrey; Debes, Jose D.; Boonstra, Andre
    Introduction and Objectives: Tolloid like protein 1 (TLL1) rs17047200 has been reported to be associated with HCC development and liver fibrosis. However, to our knowledge, no studies have been performed on Latin Americans and comparative differences between TLL1 rs17047200 in HCC patients from Latin America and Europe are undefined. Materials and Methods: Cross-sectional analysis performed on Latin American and European individuals. We analyzed TLL1 rs17047200 on DNA from 1194 individuals, including 420 patients with HCC (86.0 % cirrhotics) and 774 without HCC (65.9 % cirrhotics). Results: TLL1 rs17047200 genotype AT/TT was not associated with HCC development in Latin Americans (OR: 0.699, 95 %CI 0.456-1.072, p = 0.101) or Europeans (OR: 0.736, 95 %CI 0.447-1.211, p = 0.228). TLL1 AT/TT was not correlated with fibrosis stages among metabolic dysfunction-associated steatotic liver disease (MASLD) patients from Latin America (OR: 0.975, 95 %CI 0.496-1.918, p = 0.941). Among Europeans, alcohol-related HCC had lower TLL1 AT/TT frequencies than cirrhosis (18.3 % versus 42.3 %, OR: 0.273, 95 %CI 0.096-0.773, p = 0.015). Conclusions: We found no evidence that the TLL1 rs17047200 AT/TT genotype is a risk factor for HCC develop-ment in Latin Americans or Europeans. A larger study integrating ethnic and etiology backgrounds is needed to determine the importance of the TLL1 SNP in HCC development.(c) 2023 Fundacion Clinica Medica Sur, A.C. Published by Elsevier Espana, S.L.U. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/)
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    Genetic Risk Score Correlates with Immune Profile and Risk of HCC and Cirrhosis development in Hispanics with MASLD
    (2025) Fu, Siyu; Groothuismink, Anthonie; Balderramo, Domingo; Mattos, Angelo Z.; Hoppe, Lisia; Carrera, Enrique; Diaz-Ferrer, Javier; Prieto, Jhon; Banales, Jesus M.; Arrese Jímenez, Marco Antonio; Hansen, Bettina E.; Boonstra, Andre; Debes, José D.
    Genetic risk score and immune dysregulations have been separately associated with the development of hepatocellular carcinoma (HCC) and cirrhosis in the context of metabolic associated steatotic liver disease (MASLD). Latin America has the highest prevalence of MASLD worldwide. However, the relationship between genetic risk scores, immune dysregulation and MASLD has not been explored.
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    Validation and optimization of AFP-based biomarker panels for early HCC detection in Latin America and Europe
    (2023) Beudeker, Boris J. B.; Fu, Siyu; Balderramo, Domingo; Mattos, Angelo Z.; Carrera, Enrique; Diaz, Javier; Prieto, Jhon; Banales, Jesus; Vogel, Arndt; Arrese, Marco; Oliveira, Jeffrey; Groothuismink, Zwier M. A.; van Oord, Gertine; Hansen, Bettina E.; de Man, Robert A.; Debes, Jose D.; Boonstra, Andre
    Background: HCC is a major cause of cancer death worldwide. Serum biomarkers such as alpha-fetoprotein (AFP), protein induced by vitamin K absence-II, and the Gender, Age, AFP-L3, AFP, Des-gamma-carboxy prothrombin (GALAD) score have been recommended for HCC surveillance. However, inconsistent recommendations in international guidelines limit their clinical utility.Methods: In this multicenter study, over 2000 patient samples were collected in 6 Latin American and 2 European countries. The performance of the GALAD score was validated in cirrhotic cases, and optimized versions were tested for early-stage HCC and prediagnostic HCC detection.Results: The GALAD score could distinguish between HCC and cirrhosis in Latin American patients with an AUC of 0.76, sensitivity of 70%, and specificity of 83% at the conventional cutoff value of -0.63. In a European cohort, GALAD had an AUC of 0.69, sensitivity of 66%, and specificity of 72%. Optimizing the score in the 2 large multicenter cohorts revealed that AFP-L3 contributed minimally to early-stage HCC detection. Thus, we developed a modified GALAD score without AFP-L3, the ASAP (age, sex, AFP, and protein induced by vitamin K absence-II), which showed promise for early-stage HCC detection upon validation. The ASAP score also identified patients with cirrhosis at high risk for advanced-stage HCC up to 15 months before diagnosis (p < 0.0001) and differentiated HCC from hemangiomas, with a specificity of 100% at 71% sensitivity.Conclusion: Our comprehensive analysis of large sample cohorts validates the GALAD score's utility in Latin American, Spanish, and Dutch patients for early-stage HCC detection. The optimized GALAD without AFP-L3, the ASAP score, is a good alternative and shows greater promise for HCC prediction.