Transcriptome Analysis Reveals the Differential Inflammatory Effects Between Propofol and Sevoflurane During Lung Cancer Resection: a Randomized Pilot Study

Abstract

Background: Propofol and sevoflurane are two commonly used anesthetics perioperatively. It showed that anesthetic drugs may have an effect on tumorigenesis. Previous researches mostly focused on in vitro experiments, the specimens collected were mostly peripheral body fluid, lacking direct evidence of the impact of anesthetic drugs on human tissues. This study aims at elucidating the effects of propofol and sevoflurane on lung cancer using next-generation sequencing through an in vivo experiment. Methods: Patients were randomly assigned to a group either receiving propofol or sevoflurane during surgery. Then patients’ tumor and paired normal samples were collected and sequenced by next-generation sequencing. Differentially expressed genes (DEG) were analyzed by two statistical models, then cluster analysis, PCA, GO ontology and KEGG pathways analysis were done. Candidate genes were confirmed by qRT-PCR. Results: Two study groups demographic data were not statistically significant. Through single factor model analysis, 810 DEG in propofol group and 508 DEG in sevoflurane group were obtained. In order to better reflect the differential effects of propofol and sevoflurane, in the meanwhile reduce false positives of DEG, we used multi-factor model analysis, which resulted in 124 DEG. In PCA and cluster analysis, four groups (propofol cancer group, propofol normal group, sevoflurane cancer group, sevoflurane normal group) were separated adequately, indicating the accuracy of DEG. We chose seven significant pathways (Cellular response to interleukin-1, Chemokine-mediated signaling pathway, Chemokine signaling pathway, Cytokine-cytokine receptor interaction, Inflammatory response, Immune response, TNF signaling pathway) for downstream analysis. From qRT-PCR results, three genes (CXCR1, CXCL8 and TNFAIP3) were confirmed. Conclusions: Through RNA-seq analysis, the effects of propofol and sevoflurane during lung cancer resection were different, and mainly differ in inflammatory related pathways which might be possibly by targeting CXCL8.Trial registration: Trial registry number was ChiCTR1900026213 (http://www.chictr.org.cn/showproj.aspx?proj=43733).