Omega-3 fatty acid improves the clinical outcome of hepatectomized patients with hepatitis B virus(HBV)-associated hepatocellular carcinoma

Omega-3 fatty acid supplemented total parenteral nutrition improves the clinical outcome of patients undergoing certain operations; however, its benefits for patients with hepatitis type B virus (HBV)-associated hepatocellular carcinoma (HCC) who have undergone hepatectomy are still not clear. The aim of this study was to evaluate the effect of omega-3 fatty acid supplemented total parenteral nutrition on the clinical outcome of patients with HBV- associated HCC who underwent hepatectomy at our institution. A total of 63 patients with HBV-associated HCC who underwent hepatectomy were included in this study. These patients were randomly assigned to receive stand- ard total parenteral nutrition (the control group, n = 31) or omega-3 fatty acid supplemented total parenteral nutri- tion (the omega-3 fatty acid group, n = 32) for at least 5 d. The study endpoints were the occurrence of infection- related complications, recovery of liver function and length of hospital stay. The results showed that the omega-3 fatty acid group had a lower infection rate (omega-3 fatty acid, 19.4% vs control, 43.8%, P 〈 0.05), a better liver function after hepatectomy: alanine transaminase (omega-3 fatty acid, 48.23__+ 18.48 U/L vs control, 73.34 q-40.60 U/L, P 〈 0.01), aspartate transaminase (omega-3 fatty acid, 35.77_ 14.56 U/L vs control, 50.53 4-24.62 U/L, P 〈 0.01), total bilirubin (omega-3 fatty acid, 24.29___7.40 mmol/L vs control, 28. 374-8.06 mmol/L, P 〈 0.05) and a shorter length of hospital stay (omega-3 fatty acid, 12.71 ___2.58 d vs control, 15.91 ___3.23 d, P 〈 0.01). The serum contents of IL-6 (omega-3 fatty acid, 23.98___5.63 pg/mL vs control, 35.55___7.5 pg/mL, P 〈 0.01) and TNF-a (ome- ga-3 fatty acid, 4.43___1.22 pg/mL vs control, 5.96___1.58 pg/mL, P 〈 0.01) after hepatectomy were significantly lower in the omega-3 fatty acid group than those of the control group. In conclusion, administration of omega-3 fatty acid may reduce infection rate and improve liver function recovery in HBV-associated HCC patients after hepatectomy. This improvement is associated with suppressed production of proinflammatory cytokines in these patients.

HIF-1α-induced expression of m6A reader YTHDF1 drives hypoxia-induced autophagy and malignancy of hepatocellular carcinoma by promoting ATG2A and ATG14 translation

N6-methyladenosine(m6A),and its reader protein YTHDF1,play a pivotal role in human tumorigenesis by affecting nearly everystage of RNA metabolism.Autophagy activation is one of the ways by which cancer cells survive hypoxia.However,the possibleinvolvement of m6A modification of mRNA in hypoxia-induced autophagy was unexplored in human hepatocellular carcinoma(HCO).In this study,specific variations in YTHDF1 expression were detected in YTHDF1-overexpressing,knockout,and-knockdownHCC cells,HCC organoids,and HCC patient-derived xenograft(PDX)murine models.YTHDF1 expression and hypoxia inducedautophagy were significantly correlated in vitro;signifhcant overexpression of YTHDF1 in HCC tissues was associated with poorprognosis,Multivariate cox regression analysis identihed YTHDF1 expression as an independent prognostic factor in patients withHCC.Multiple HC models conhrmed that YTHDF1 deficiency inhibited HCC autophagy,growth,and metastasis.Luciferase reporterassays and chromatin immunoprecipitation demonstrated that HlIF-1a regulated YTHDF1 transcription by directly binding to itspromoter region under hypoxia.The results of methylated RNA immunoprecipitation sequencing,proteomics,and polysomeprofling indicated that YTHDF1 contibuted to the translation of autophagy-related genes ATG2A and ATG14 by binding to m6A-modifhed ATG2A and ATG14 mRNA,thus facilitating autophagy and autophagy-related malignancy of HCC.Taken together,HlE-1d-induced YTHDF1 expression was associated with hypoxia-induced autophagy and autophagy-related HCC progression via promoting translation of autophagy-related genes ATG2A and ATG14 in a m6A-dependent manner.Our fndings suggest thatYTHDF1 is a potential prognostic biomarker and therapeutic target for patients with HCC.