Elevated expression of CK19, Ki67, and β-Catenin as prognostic biomarkers in hepatocellular carcinoma

CK19、Ki67 和 β-catenin 的高表达可作为肝细胞癌的预后生物标志物

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Abstract

BACKGROUND: Cytokeratin 19 (CK19), Ki67 antigen (Ki67), and β-catenin are abnormally overexpressed in hepatocellular carcinoma (HCC), but their diagnostic and prognostic value remains unclear. This study aims to investigate the predictive role of these three markers in post-operative survival of HCC patients. METHODS: The expression levels of CK19, Ki67, and β-catenin in HCC tumor tissues were determined through public datasets. Kaplan-Meier survival analysis and multivariate Cox regression were performed to evaluate their prognostic value. Immunohistochemistry and Western blotting were used to detect the expression levels of CK19, Ki67, and β-catenin in hepatocellular carcinoma tissues and adjacent non-cancerous tissues. Transcriptome sequencing was performed to analyze the differential transcriptional changes between HCC and adjacent non-cancerous tissues. A cohort of HCC post-operative patients was included to analyze the correlation between the three markers and clinical pathological features. RESULTS: CK19, Ki67, and β-catenin were highly expressed in HCC tissues and lowly expressed in adjacent non-cancerous tissues. High expression of CK19, Ki67, and β-catenin was closely associated with poor disease-free survival (DFS) and overall survival (OS) in HCC patients' post-surgery. These three markers serve as independent prognostic factors for DFS and OS. Immunohistochemistry and Western blotting revealed upregulation of CK19, Ki67, and β-catenin in HCC tissues, while transcriptome sequencing indicated alterations related to metabolic reprogramming, immune evasion, and invasion/metastasis in HCC. Clinical data from HCC patients showed that CK19 expression correlated with tumor number and differentiation grade, Ki67 expression correlated with patient age, tumor size, tumor number, lymphatic metastasis, and tumor differentiation, while β-catenin expression was closely related to tumor diameter, number, and capsule status. CONCLUSION: CK19, Ki67, and β-catenin are highly expressed in HCC and can serve as molecular markers for post-operative recurrence and poor survival in HCC patients, providing a basis for precise prognostic evaluation in HCC.

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