Zhong Xu

Supporting tables for proteomics datasets

Figure S3 from HBV Remodels PP2A Complexes to Rewire Kinase Signaling in Hepatocellular Carcinoma

Supplementary methods and figure legends

This meta-analysis assessed the clinicopathological significance of GLI1 in hepatocellular carcinoma (HCC). We systematically searched PubMed, Web of Science, Embase, Cochrane Library, Wan Fang, and CNKI for studies through October 2025. Studies assessing GLI1 by immunohistochemistry in HCC tissue and reporting its clinicopathological correlations were included. Study quality was evaluated using the Newcastle-Ottawa Scale. Pooled odds ratios (ORs) with 95% confidence intervals (CIs) were calculated. Publication bias and sensitivity analyses were performed, and subgroup analyses were conducted when > 4 studies were available. Analysis of ten studies (n = 974) showed significant GLI1 upregulation in HCC versus non-tumorous tissues (OR = 7.06, 95% CI 3.21–15.54, P < 0.0001). Elevated GLI1 was associated with intrahepatic metastasis (OR = 2.51, 95% CI 1.42–4.43, P = 0.002), vascular invasion (OR = 2.98, 95% CI 1.64–5.42, P < 0.001), hepatitis B virus (HBV) infection (OR = 2.32, 95% CI 1.28–4.20, P = 0.006). The significance of advanced pTNM stage (OR = 3.03, 95% CI 1.29–7.10, P = 0.011) disappeared after adjusting for publication bias (adjusted OR = 1.94, 95% CI 0.85–4.40). No significant associations were found with patient age, liver cirrhosis, serum AFP level, and tumor size. Findings are based on observational studies with heterogeneity in GLI1 assessment; evidence certainty for several outcomes is low or very low. These findings support the hypothesis that GLI1 might be involved in aggressive HCC phenotypes and warrant its investigation in future, standardized prospective studies to assess its potential clinical utility. Trial registration: The study protocol was registered in the International Prospective Register of Systematic Reviews (CRD42024500731).

Giant common bile duct stones are hard to extract, with high adverse events and recurrence, and single treatments have limitations. This study explores managing them with endoscopic retrograde cholangiopancreatography (ERCP) combined with percutaneous transhepatic cholangial drainage (PTCD) sinus tract. A 66-year-old man with recurrent common bile duct stones (multiple large extrahepatic stones) complicated by cholangitis and acute liver failure was admitted. He first received PTCD with T-tube drainage, ERCP for stone extraction, and stent placement. Three months later, a 71 × 30-mm stone was found and successfully fragmented via PTCD sinus tract and 2 ERCP sessions with electrohydraulic lithotripsy, without complications. This combined technique enables minimally invasive staged drainage, lithotripsy, and stone extraction for complex giant stones, providing early drainage with minimal trauma and a new strategy for recurrent or high-risk patients.

The implications of AKT and phospho-AKT (p-AKT) expression patterns in various malignancies remain a subject of considerable scientific interest. Current evidence regarding their association with hepatocellular carcinoma (HCC) progression by immunohistochemical (IHC) analyses demonstrates significant inconsistencies. This study aimed to evaluate the clinical significance of AKT and p-AKT expression in HCC patients, with specific emphasis on their correlations with clinicopathological parameters, to provide insights to inform clinical decision-making. We conducted a systematic literature search across six major electronic databases through February 25, 2024, using search terms related to AKT, p-AKT, IHC, and hepatocellular carcinoma. Eligible studies were selected through strictly screening according to the inclusion/exclusion criteria, with methodological quality assessed via the Newcastle-Ottawa Scale (NOS). Statistical analyses were performed using Stata 15.0 software. A total of 17 eligible publications with a total of 1595 patients were analyzed in the meta-analysis. AKT overexpression in HCC correlated with advanced TNM stage (OR = 3.698, 95% CI = 1.224–11.167), vascular invasion (4.121;1.483–11.447), lymph node metastasis (2.958;1.188–7.367), capsule integrity compromise (2.491;1.192–5.206), and portal vein cancer thrombus (6.919;1.240-38.619). p-AKT expression in HCC demonstrated associations with tumor grade (2.789;1.379–5.641), TNM stage progression (3.058;1.779–5.255), tumor size > 5 cm (2.507;1.056–5.953), portal vein cancer thrombus (4.280;1.798–10.188), and cirrhotic history (1.933;1.226–3.047). For results with significant heterogeneity, we used a random-effects model to pool the effect sizes and conducted subgroup analyses as well as meta-regression analyses. The results indicated that some differences between p-AKT and antibody thresholds were also observed in the subgroup of antibody thresholds, which deserves further research. Expression of AKT is associated with TNM stages, venous vascular invasion, metastasis of lymph node, integrity of capsule and portal vein cancer thrombus. And p-AKT expression is associated with histological grades, portal vein cancer thrombus, liver cirrhosis, tumor size and TNM stages. This synthesis establishes AKT as a biomarker for advanced HCC features including metastatic potential and vascular complications, while p-AKT demonstrates dual associations with both tumor progression markers and underlying hepatic pathology.

Introduction: Accumulating evidence indicates that antioxidants promote tumor growth and metastasis after tumor onset in several cancer types. However, whether antioxidants prevent or accelerate hepatic tumorigenesis during steatosis remains unknown. Therefore, we investigated the effects of resveratrol (RES) and N-acetylcysteine (NAC) on hepatocellular carcinoma (HCC) development using two fatty liver mouse models.Methods: High-fat diet (HFD) plus diethylnitrosamine (DEN)- and AKT/Ras-induced primary HCC mouse models were used. The weight, liver weight ratio and the number of HCC tumors were calculated and histological features of mouse HCC tissues were analyzed using immumohistochemical staining such as hematoxylin and eosin staining. Proteomic analysis was used to screen for differences in liver cancer progression between antioxidant-treated HCC and models. Protein inhibitor recovery experiments in mice and in vitro cells validate the targets screened by proteomic analysis. The expression of GST-pi, p-JNK and p-p38 signaling molecules in HCC were investigated using Western blotting.Results: RES and NAC enhance HCC formation in both DEN/HFD and AKT/Ras mice. RES and NAC alleviate hepatosteatosis, and reduce ROS and DNA damage in mice. Proteomic analysis and protein inhibitor recovery assay demonstrated that GST-pi is a therapeutic target for antioxidant-induced hepatocellular carcinoma growth. Mechanistically, RES and NAC decreased p-JNK and p-p38, the two major mitogen-activated protein kinases, in HCC cells. Blockade of GST-pi abrogated the reduction in p-JNK and p-p38 levels and increased apoptosis of HCC cells.Conclusion: Antioxidants may increase the incidence of HCC in a population with fatty liver, despite reduction in ROS production, by inhibiting GST-pi-MAPK axis.