Intraoperative use of dexmedetomidine in patients with hepatocellular carcinoma: prognostic impact and mechanism analysis

Abstract

Abstract: Objective: The aim is to investigate the impact of intraoperative dexmedetomidine (DEX) on the prognosis of patients with hepatocellular carcinoma (HCC) and to investigate the underlying mechanisms.
Methods: Retrospective analysis of clinical data of 144 HCC patients undergoing hepatectomy in Lu’an Hospital of Anhui Medical University from January 2019 to January 2023. The association between DEX and the prognosis of HCC patients was determined by univariate and multifactorial Cox risk regression. To resolve DEX cancer-promoting mechanisms by bioinformatics, western blotting, immunohistochemistry and various online databases.
Results: 144 patients were followed up for 6-48 months with a mean follow-up time of 32.9 months, including 63 recurred and 57 patients died. Patients with intraoperative DEX had lower recurrence-free survival (P<0.05) and overall survival (P<0.05) than those without DEX. Univariate combined with multifactorial Cox risk regression analysis identified intraoperative DEX use as an independent risk factor for recurrence and death in HCC patients (P<0.05). Six DEX-regulated genes were identified based on the GSE188867 dataset and the TCGA-HCC cohort: CCDC34, E2F8, CENPH, CTHRC1, CENPW, and E2F1. Western blotting and IHC results showed that E2F8 and E2F1 expression was increased in HCC tissues (P<0.05) and was rapidly upregulated by DEX (P<0.05). Computerized molecular docking models showed that DEX stably formed hydrogen bonds with ARC-267 and LYS-264 residues in E2F8 at a binding energy of -6.7 kcal/mol and with TYR-746 residues in E2F1 at an energy of -5.0 kcal/mol. The results of gene set enrichment analysis (GSEA) highlighted that DEX could rapidly activate cell cycle signaling (P<0.05).
Conclusion: Intraoperative systemic administration of DEX mediates a worse prognosis in patients with HCC, a process that involves DEX's rapid activation of cell cycle signaling, including possible direct binding to E2F8 and E2F1. DEX should be used with caution in patients with HCC.

Key words: Hepatocellular carcinoma, Dexmedetomidine, Prognosis, Western blotting, Immunohistochemistry, Molecular docking

Shao Chaoyan, Ma Zhonglin, Wu Wei, Wu Song, Zheng Lidong. Intraoperative use of dexmedetomidine in patients with hepatocellular carcinoma: prognostic impact and mechanism analysis[J]. Electronic Journal of Liver Tumor, 2024, 11(3): 42-53.

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