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Background: Although several studies have found that the serum lipid profile may be correlated with hepatocellular carcinoma (HCC), the causal relationships between the serum lipid profile and HCC have not been determined due to potential confounder. Here, Mendelian randomization (MR) analysis was performed to identify the relationship between the serum lipid profile and HCC in the East Asian population., Method: Our study made a MR analysis with the validation of two data sets. We obtained genome-wide association study (GWAS) data related to the serum lipid profile from Asian Genetic Epidemiology Network (AGEN). Then, the data from a recent large GWAS of the East Asian ancestry in Japan (BioBank Japan, BBJ) were extracted. Summary-level statistical data for HCC were obtained from a large GWAS of the East Asian ancestry in Japan. Univariable MR analysis were performed to identify whether the genetic evidence of serum lipid profile was significantly associated with HCC risk. Multivariable MR analysis was conducted to estimate the independent effects of exposures on HCC., Results: Univariable and multivariable MR analyses indicated that the serum lipid profile was not a risk factor for HCC incidence in either data set based on the East Asian population. Multivariable MR analysis revealed that the hazard ratios of the probability of HCC in AGEN were 1.134 (95% confidence interval (CI), 0.903-1.424) for TG, 1.010 (95% CI: 0.824-1.237) for HDL-C, 0.974 (95% CI: 0.746-1.271) for TC, 0.918 (95% CI: 0.734-1.147) for LDL-C, while the results in BBJ were also non-significant: 1.111 (95% CI: 0.869-1.419) for TG, 0.957 (95% CI: 0.790-1.158) for HDL-C, 0.917 (95% CI: 0.643-1.308) for TC, 0.932 (95% CI: 0.699-1.243) for LDL-C., Conclusion: Our MR study with the validation of two data sets found no strong evidence to support causal associations between the serum lipid profile and HCC risk., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper, (© 2023 The Authors.)

Introduction: Hepatocellular carcinoma (HCC) is one of the most common malignant tumours worldwide. Clarification of the somatic mutational landscape of important genes could reveal new therapeutic targets and facilitate individualized therapeutic approaches for HCC patients. The mutation and expression changes in the ARID1A gene in HCC remain controversial., Methods: First, cBioPortal was used to visualize genetic alterations and DNA copy number alterations (CNAs) in ARID1A. The relationships between ARID1A mutation status and HCC patient clinicopathological features and overall survival (OS) were also determined. Then, a meta-analysis was performed to evaluate the effect of ARID1A mutation or expression on the prognosis of HCC patients. Finally, the role of ARID1A in HCC progression was verified by in vitro experiments., Results: ARID1A mutation was detected in 9.35% (33/353) of sequenced HCC cases, and ARID1A mutation decreased ARID1A mRNA expression. Patients with ARID1A alterations presented worse OS than those without ARID1A alterations. Meta-analysis and human HCC tissue microarray (TMA) analysis revealed that HCC patients with low ARID1A expression had worse OS and relapse-free survival (RFS), and low ARID1A expression was negatively correlated with tumour size. Then, ARID1A gain-of-function and loss-of-function experiments demonstrated the tumour suppressor role of ARID1A in HCC in vitro . In terms of the mechanism, we found that ARID1A could inhibit HCC progression by regulating retinoblastoma-like 1 (RBL1) expression via the JNK/FOXO3 pathway., Conclusions: ARID1A can be considered a potential prognostic biomarker and candidate therapeutic target for HCC., Competing Interests: The authors declare no competing interests., (© 2023 The Authors. Published by Elsevier Ltd.)