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Biological Progress, including 'GOBP_ACETYLCHOLINE_-METABOLIC_PROCESS', 'GOBP_L_KYNURENINE_META-BOLIC_PROCESS', and 'GOBP_N_ACYLETHANOLAMINE_METABOLIC_PROCESS' according to the GSEA and GSVA results. Therefore, we established a classifier that can divide different HCV-related HCC patients into 4 subgroups, including EphA2+/Meta+, EphA2+/Meta-, EphA2-/Meta+, EphA2-/Meta-. The scatter plot map shows different genes expression of different subtypes. Moreover, it's obvious the 'EphA2+/Meta+' subtype has the lowest median survival and overall survival (P<0.01). Conclusion Our work revealed that there is another important role of EphA2, except for the migration, adhesion, proliferation, and differentiation, it's also metabolism-related. It helps us to understand more comprehensively the function of EphA2 in the cancer cells and the carcinogenesis of HCV. Both of them will improve the understanding the HCV-related hepatocellular carcinoma and the development of anti-cancer treatment.

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Background and aims: Non-alcoholic fatty liver disease (NAFLD) is a complex trait that has a global prevalence estimated as 25%. We aimed to identify the genetic variant underlying a four-generation family with progressive NAFLD leading to cirrhosis, decompensation and development of hepatocellular carcinoma in the absence of common risk factors such as obesity and type 2 diabetes. Methods: Exome sequencing and genome comparisons were used to identify the likely causal variant. We extensively characterised the clinical phenotype and post-prandial metabolic responses of family members with the identified novel variant in comparison to healthy non-carriers and wild type patients with NAFLD. Variant-expressing hepatocyte-like cells (HLCs) were derived from human induced pluripotent stem cells generated from homozygous donor skin fibroblasts. The phenotype was assessed using imaging, targeted RNA analysis and molecular expression arrays. Results: We identified a rare causal variant in MTTP, c.1691T>C p.I564T (rs745447480) encoding microsomal triglyceride transfer protein (MTP) associated with progressive non-alcoholic fatty liver disease, unrelated to metabolic syndrome. Although other described mutations in MTTP cause abetalipoproteinemia, neither homozygotes nor heterozygotes exhibited characteristic manifestations of this severe disease. HLCs derived from a homozygote donor had lower lipoprotein ApoB secretion, compared to wild type cells. Cytoplasmic triglyceride accumulation in HLCs triggered endoplasmic reticulum stress, secretion of pro-inflammatory mediators and production of reactive oxygen species. Conclusion: We have identified and characterized a rare causal variant in MTTP and homozygosity for MTTP p.I564T is associated with progressive NAFLD without any other manifestations of abetalipoproteinemia.

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