VAMP5 Mediates Sevoflurane-Induced Immune Modulation in Cervical Cancer: A Clinical Translational Study
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Published on: October 23, 2018
Zengzhen Zhang1, Xianning Dong2, Tingting Yu1
1Department of Anesthesiology Shandong Provincial Third Hospital Shandong University Jinan Shandong 250031 China sdu.edu.cn.
Background:
Sevoflurane, a commonly used inhaled anesthetic, has been implicated in modulating tumor biology and perioperative immune responses, yet the underlying molecular mechanisms remain poorly understood. This study aims to investigate whether sevoflurane regulates key immune-related genes in cervical cancer patients undergoing laparoscopic radical hysterectomy (LRH) and to explore the clinical relevance of such regulation.
Methods:
Based on prior RNA-seq screening, we established a two-step validation framework to identify sevoflurane-regulated genes in a clinical cohort. A total of 116 cervical cancer patients undergoing LRH were enrolled, including 70 who received sevoflurane anesthesia and 46 who received propofol anesthesia. Peripheral blood samples were collected at five perioperative time points. mRNA expression levels of candidate genes were measured by qRT-PCR, lymphocyte subsets were analyzed by flow cytometry, and VAMP5 protein expression was assessed by intracellular staining. Bioinformatics analyses were performed using TCGA data to evaluate associations between candidate genes and tumor immune infiltration.
Results:
MAP3K7 and VAMP5 were validated as sevoflurane-downregulated targets, showing sustained suppression postoperatively compared to the propofol group. VAMP5 expression correlated significantly with tumor progression and immune cell infiltration in cervical cancer, particularly CD8+ T-cells, B-cells, and macrophages. Among sevoflurane-treated patients, those with lower VAMP5 expression exhibited delayed postoperative recovery of CD8+ T-cell counts at 48 and 72 h after surgery, whereas no such difference was observed for other lymphocyte subsets.
Conclusions:
This study identify VAMP5 as a novel molecular link between anesthetic choice and immune modulation, suggesting that sevoflurane may influence perioperative immune recovery through vesicle-associated mechanisms, with potential implications for optimizing anesthesia strategies to improve oncologic outcomes.
