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Objective: The purpose of this study was to discuss the relationship between genetic polymorphism of promoter region let-7 and genetic susceptibility to hepatocellular carcinoma (HCC) in Chinese population.
Methods: In this case-control study, 1300 cases of HBV positive patients were recruited in case group and another 1344 cases of persistent chronic HBV carriers were selected as control. 5 ml of blood sample was collected from each subject, from which the DNA was extracted; and rs10877887 and rs13293512 in promoter region let-7 were selected as the study sites. The polymorphism was detected by TaqMan allelic discrimination assay and the OR value (95%CI) was evaluated by Logistic Regression Method to analyze the relationship between susceptibility to HCC and different genotypes.
Results: The frequencies of genotype TT, CT and CC in site rs10877887 were 43.0% (542/1261), 44.7% (564/1261) and 12.3% (155/1261) respectively in case group; while separately 44.0% (581/1319), 44.4% (585/1319) and 11.6% (153/1319)in control group. The frequencies of genotype TT, CT and CC in site rs13293512 were 32.0% (406/1270), 48.1% (611/1270) and 19.9% (253/1270) respectively in case group; while separately 33.1% (427/1291), 49.4% (638/1291) and 17.5% (226/1291) in control group. The results of multifactor logistic regression analysis showed no statistical significance in the relationship between different genotype TT, mutated genotype C in site rs10877887 and susceptibility to HCC (CC + CT vs TT, adjusted OR = 1.05, 95%CI: 0.90 - 1.23); and either no statistical significance in the relationship between different genotype TT, mutated genotype C in site rs13293512 and susceptibility to HCC (CC + CT vs TT, adjusted OR = 1.06, 95%CI: 0.89 - 1.25). The united-analysis of the two sites showed the frequencies of 0, 1, 2 and 3-4 mutated-genotype C were 13.3% (164/1235), 36.2% (447/1235), 33.0% (408/1235) and 17.5% (216/1235) respectively in case group; and separately 14.2% (181/1269), 37.0% (469/1269), 33.1% (420/1269) and 15.7% (199/1269) in control group. The susceptibility to HCC in 1,2,3-4 mutated-genotype C carriers were 1.05 (0.81 - 1.34), 1.07 (0.83 - 1.38) and 1.22 (0.91 - 1.62) times of the non-mutated genotype subjects; but there was no statistical significance (Wald χ(2) = 1.79, P = 0.181).
Conclusion: The polymorphism of study sites rs10877887 and rs13293512 may not be the biomarker of susceptibility to HCC in Chinese.
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Front Biosci (Landmark Ed)
August 2025
Department of Hepatobiliary and Pancreatic Surgery, Peking University Shenzhen Hospital, 518036 Shenzhen, Guangdong, China.
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September 2025
Liver Cancer Institute, Zhongshan Hospital, Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Fudan University, Shanghai 200032, China; Clinical Center for Biotherapy, Zhongshan Hospital; Fudan University, Shanghai 200032, China. Electronic address: wu.weizhong@zs-hospital
Background: Ferroptosis, a novel type of regulated cell death driven by iron-dependent lipid peroxide accumulation, represents a promising therapeutic strategy for aggressive cancers. However, the molecular mechanism of ferroptosis in hepatocellular carcinoma (HCC) remains elusive.
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Cancers (Basel)
August 2025
Weill Cornell Medicine, New York, NY 10021, USA.
The liver's susceptibility to age-related diseases, including hepatocellular carcinoma (HCC), is increasingly linked to progressive epigenetic alterations that disrupt gene regulation, promote fibrosis, and impair regeneration. While glucagon-like peptide-1 receptor agonists (GLP-1RAs) are well-established in the treatment of type 2 diabetes and obesity, emerging evidence suggests they may also exert protective effects on the liver through the modulation of epigenetic pathways. In this perspective, we explore the hypothesis that GLP-1RAs may help restore a healthier epigenetic state in the aging liver by influencing mechanisms such as DNA methylation, histone modification, and non-coding RNA activity.
View Article and Find Full Text PDFWorld J Transplant
September 2025
J C Walter Jr Transplant Center, Sherrie and Alan Conover Center for Liver Disease and Transplantation, Department of Surgery, Houston Methodist Hospital, Houston, TX 77030, United States.
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View Article and Find Full Text PDFJ Hepatol
August 2025
Faculty of Biochemistry and Molecular Medicine and Biocenter Oulu, University of Oulu, P.O. Box 3000, 90014, Oulu, Finland.
The liver exhibits pronounced sexual dimorphism, characterised by sex-specific differences in structure, metabolic function, and susceptibility to disease. Although traditionally considered homogeneous, the liver exhibits significant zonal heterogeneity, with periportal and pericentral regions differing considerably in terms of oxygen availability, metabolic activity and partially cell composition. In recent years, new technologies such as single-cell RNA sequencing and spatial proteomics have revealed numerous sex-specific differences in gene and protein expression that align with the spatial heterogeneity of liver functions.
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