Dominik Buschmann1, Florian Brandes2/3, Anja Lindemann3, Melanie Maerte2, Petra Ganschow4, Alexander Chouker2, Gustav Schelling2, Michael W. Pfaffl1, Marlene Reithmair3
1) Division of Animal Physiology and Immunology, Technical University of Munich, Freising, Germany;
2) Department of Anesthesiology, University Hospital, Ludwig-Maximilians-University Munich, Munich, Germany;
3) Institute of Human Genetics, University Hospital, Ludwig-Maximilians-University Munich, Munich, Germany;
4) Department of General, Visceral, and Transplant Surgery, Ludwig-Maximilians-University Munich, Munich, Germany;
Even though tumor resection is crucial for survival of patients with solid tumors, surgery itself might promote tumor progression and metastasis. Data from both experimental and retrospective cohort studies suggest that using volatile anesthetic gases (VAG) during cancer surgery may enhance tumor growth and metastasis compared to surgery using total intravenous anesthesia (TIVA). For colorectal cancer surgery, overall and disease-free survival is significantly better in patients anesthetized with TIVA as opposed to VAG. Circulating cell-free miRNAs including those associated with extracellular vesicles are crucial mediators of malignant cell-to-cell communication and metastasis and might play a role in mediating these differential effects of anesthetics on tumor progression.
In this study, we characterized circulating extracellular miRNAs in a cohort of colorectal cancer surgery patients anesthetized using propofol (TIVA, n=8) or sevoflurane (VAG, n=9). Sera were sampled before anesthesia and after tumor resection at termination of surgery, and circulating miRNAs were profiled by Next-Generation Sequencing. Next, we assessed perioperative changes in miRNA expression induced by either anesthetic drug and compared their biological effects on tumor-relevant pathways.
Post-operative miRNA profiles were shifted in both anesthetic groups, resulting in clear separation of pre- and post-operative samples. Despite a significant overlap in miRNAs upregulated in both groups, we detected five (sevoflurane) and 36 (propofol) miRNAs to be specifically responsive to either anesthetic agent. In silico target analyses of miRNA expression patterns indicated an inhibitory effect of propofol on crucial carcinoma-related pathways such as proliferation and migration as well as enhanced apoptosis associated with propofol. Sevoflurane-associated changes in miRNA profiles impacted these pathways to a much smaller extent or not at all.
The differential effect of anesthetic agents on outcome of cancer surgery reported by retrospective studies might therefore be in part mediated by perioperative changes of circulating extracellular miRNA profiles.
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