Abstract
Prometastatic and antitumor effects of different anesthetics have been previously analyzed in several studies with conflicting results. Thus, the underlying perioperative molecular mechanisms mediated by anesthetics potentially affecting tumor phenotype and metastasis remain unclear. It was hypothesized that anesthetic‑specific long non‑coding RNA (lncRNA) expression changes are induced in the blood circulation and play a crucial role in tumor outcome. In the present study, high‑throughput sequencing and quantitative PCR were performed in order to identify lncRNA and mRNA expression changes affected by two therapeutic regimes, total intravenous anesthesia (TIVA) and volatile anesthetic gas (VAG) in patients undergoing colorectal cancer (CRC) resection. Total blood RNA was isolated prior to and following resection and characterized using RNA sequencing. mRNA‑lncRNA interactions and their roles in cancer‑related signaling of differentially expressed lncRNAs were identified using bioinformatics analyses. The comparison of these two time points revealed 35 differentially expressed lncRNAs in the TIVA‑group, and 25 in the VAG‑group, whereas eight were shared by both groups. Two lncRNAs in the TIVA‑group, and 23 in the VAG‑group of in silico identified target‑mRNAs were confirmed as differentially regulated in the NGS dataset of the present study. Pathway analysis was performed and cancer relevant canonical pathways for TIVA were identified. Target‑mRNA analysis of VAG revealed a markedly worsened immunological response against cancer. In this proof‑of‑concept study, anesthesic‑specific expression changes in lncRNA and mRNA profiles in blood were successfully identified. Moreover, the data of the present study provide the first evidence that anesthesia‑induced lncRNA pattern changes may contribute further in the observed differences in CRC outcome following tumor resection.
Keywords:
colorectal cancer; lncRNA; signaling pathways; target‑mRNA; total intravenous anesthesia; volatile anesthetic gas.