Effect and mechanism analysis of low-dose ETO in adjuvant to PRO anesthesia induction for postoperative prognosis of hepatocellular carcinoma

Abstract

Abstract: Objective: To analyze the prognostic impact of low-dose etomidate (ETO) assisted propofol (PRO) induction of total intravenous anesthesia on patients with hepatocellular carcinoma (HCC) and to explore the underlying biological mechanisms.
Methods: Eighty-four HCC patients admitted to our hospital from January 2021 to January 2023 were selected. The patients were divided into a control group (n=42) and an experimental group (n=42) according to the randomized numerical table method; the control group was induced by PRO total intravenous anesthesia, and the experimental group was induced by a small dose of ETO-assisted PRO total intravenous anesthesia. The Kaplan-Meier method was employed for survival analysis.The relationship between ETO and the prognosis of HCC patients was determined by univariate and multivariate Cox regression model. Potential biological mechanisms of ETO in HCC radical resection patients were explored by bioinformatics, microarray data, enzyme-linked immunosorbent assay and molecular docking and kinetic modeling.The relationship between ETO and the prognosis of HCC patients was determined by univariate and multivariate Cox regression model.
Results: The recurrence-free survival and overall survival of patients in the experimental group were higher than those of patients in the control group (all P<0.05). Cox regression model analysis showed that ETO was an independent protective factor for recurrence and death in HCC patients (all P<0.05), and tumor stage and CD34 were independent risk factors for recurrence and death in HCC patients (all P<0.05). The results of microarray data showed a total of 143 differentially expressed genes, which were mainly enriched in signaling pathways such as negative regulation of hematopoietic progenitor cell differentiation, mechanistic target of rapamycin(mTOR), p53, vascular endothelial growth factor A and vascular endothelial growth factor receptor 2(VEGFA ,VEGFR2), and interleukin-24(IL-24). The PPI network confirmed that CD34 was a core target gene of ETO anti-HCC. Molecular docking and kinetic modeling confirmed that ETO could bind stably to CD34 protein with a binding free energy of -29.278 kJ/mol.Cox regression model analysis showed that ETO was an independent protective factor for recurrence and death in HCC patients (all P<0.05), and tumor stage and CD34 were independent risk factors for recurrence and death in HCC patients (all P<0.05).
Conclusion: Small-dose ETO-assisted PRO total intravenous anesthesia induction regimen in patients undergoing radical resection for HCC improves prognosis better and may be related to modulation of CD34 expression.

Key words: Etomidate, Propofol, Hepatocellular carcinoma, Radical resection, Prognosis

Zhai Rui, Yu Lichun, Li Hongxiang, Zhai Yongya. Effect and mechanism analysis of low-dose ETO in adjuvant to PRO anesthesia induction for postoperative prognosis of hepatocellular carcinoma[J]. Electronic Journal of Liver Tumor, 2025, 12(4): 20-29.

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