Abstract
BACKGROUND: 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. OBJECTIVE: 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. METHOD: 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. RESULT: 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. CONCLUSION: 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.