Watt Sara Kehlet, Hasselbalch Hans Carl, Skov Vibe, Kjær Lasse, Thomassen Mads, Kruse Torben A, Burton Mark, Gögenur Ismail
Zealand University Hospital, Department of Surgery, Sygehusvej 10, 4000 Roskilde, Denmark.
Zealand University Hospital, Department of Hematology, Sygehusvej 10, 4000 Roskilde, Denmark.
Surg Oncol. 2018 Jun;27(2):208-215. doi: 10.1016/j.suronc.2018.03.002. Epub 2018 Mar 27.
Cancer surgery may represent a potential risk of enhanced growth and metastatic ability of residual cancer cells due to post-operative immune dysfunction. This study identifies changes in transcription of genes involved in immune surveillance, immune suppression and carcinogenesis in the post-operative period of laparoscopic colon-cancer surgery within an ERAS regime.
Patients undergoing elective, curatively intended laparoscopic surgery for colon cancer stage I-III UICC were included in the study. Patients followed standard of care in an ERAS setting. Whole blood gene expression profiling (WBGP) was performed on the day prior to surgery and 1, 2, 3 and 10-14 days after surgery. Samples were collected in Paxgene tubes and Labeled cDNA was fragmented and hybridized to Affymetrix GeneChip™ 2.0. Results were corrected for multiple hypothesis testing using the false discovery rate. Pathway analysis was performed through the Molecular Signature Database. Paired fold changes of gene expression were calculated for post-operative compared to pre-operative samples. A mixed effect model was used to test differential gene expression by repeated-measures ANOVA.
WBGP of 33,804 genes at five timepoints in six patients showed 302 significantly differentially expressed genes between samples from the day prior to surgery and the day after surgery. Pathway gene enrichment analysis showed a downregulation of immunologically relevant pathways. There was a significant downregulation of genes involved in T-cell receptor signaling, antigen presentation and NK-cell activity after surgery. Furthermore, there was an upregulation of cytokines related to metastatic ability, growth and angiogenesis.
Whole blood gene expression profiling revealed dysregulation of genes involved in immune surveillance, inflammation and carcinogenesis, after laparoscopic colon cancer surgery.
由于术后免疫功能障碍，癌症手术可能会使残留癌细胞的生长和转移能力增强，从而带来潜在风险。本研究确定了在加速康复外科（ERAS）模式下，腹腔镜结肠癌手术后免疫监测、免疫抑制和致癌相关基因转录的变化。
本研究纳入了接受选择性、根治性腹腔镜手术治疗国际抗癌联盟（UICC）I-III期结肠癌的患者。患者在ERAS环境中遵循标准治疗方案。在手术前一天以及手术后1、2、3和10 - 14天进行全血基因表达谱分析（WBGP）。样本收集于帕克斯基因（Paxgene）管中，标记的互补脱氧核糖核酸（cDNA）被片段化并与Affymetrix GeneChip™ 2.0杂交。使用错误发现率对结果进行多重假设检验校正。通过分子特征数据库进行通路分析。计算术后与术前样本基因表达的配对倍数变化。使用混合效应模型通过重复测量方差分析来测试差异基因表达。
六名患者在五个时间点对33,804个基因进行的WBGP显示，手术前一天和手术后一天的样本之间有302个基因存在显著差异表达。通路基因富集分析显示免疫相关通路下调。术后参与T细胞受体信号传导、抗原呈递和自然杀伤细胞（NK）活性的基因显著下调。此外，与转移能力、生长和血管生成相关的细胞因子上调。
全血基因表达谱分析显示，腹腔镜结肠癌手术后，参与免疫监测、炎症和致癌的基因失调。
