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.
摘要：
先前已经在几项研究中分析了不同麻醉剂的促转移和抗肿瘤作用，结果相互矛盾。因此，麻醉药介导的潜在影响肿瘤表型和转移的围手术期分子机制尚不清楚.据推测，麻醉剂特异性长链非编码RNA（lncRNA）表达变化在血液循环中被诱导，并在肿瘤预后中起关键作用。在本研究中,进行了高通量测序和定量PCR，以鉴定受两种治疗方案影响的lncRNA和mRNA表达变化，全凭静脉麻醉(TIVA)和挥发性麻醉气体(VAG)应用于结直肠癌(CRC)切除术。在切除之前和之后分离总血液RNA,并使用RNA测序表征。使用生物信息学分析鉴定了mRNA‑lncRNA相互作用及其在差异表达lncRNA的癌症相关信号传导中的作用。这两个时间点的比较揭示了TIVA组中35种差异表达的lncRNAs，在VAG组中有25人，而两组共有8个。TIVA组中的两个lncRNAs，在本研究的NGS数据集中，VAG组中的23个被确认为差异调节的目标mRNA。进行通路分析并鉴定用于TIVA的癌症相关规范通路。VAG的Target-mRNA分析显示针对癌症的免疫反应明显恶化。在这个概念验证研究中，在血液中lncRNA和mRNA谱的麻醉特异性表达变化被成功鉴定。此外，本研究的数据提供了第一个证据,证明麻醉诱导的lncRNA模式变化可能进一步影响肿瘤切除后观察到的CRC结局差异.
