Hou Wenyun, Pan Meng, Xiao Yi, Ge Wei
Division of Colorectal Surgery, Department of General Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
National Key Laboratory of Medical Molecular Biology & Department of Immunology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, Beijing, China.
Front Oncol. 2022 Jul 22;12:912584. doi: 10.3389/fonc.2022.912584. eCollection 2022.
Previous studies have shown that the presence of perineural invasion (PNI) is associated with a significantly worse prognosis in colorectal cancer (CRC) patients. In this study, we performed a detailed analysis of the diversity of extracellular vesicles (EV) between NPNI (non-PNI) and PNI using quantitative proteomics and aim to investigate the mechanisms underlying PNI in colorectal cancer. Quantitative proteomics technology was used to identify the proteome of serum-purified EVs from CRC patients with and without PNI (PNI and non-PNI (NPNI) groups, respectively) and healthy volunteers. Mass spectrometry data were verified by ELISA and Western blot analyses. The proteomic profile of serum EVs from the PNI group differed from that of those in the NPNI group. Serum-derived EVs from the PNI promoted more significant cellular mobility than EVs derived from the NPNI group. EV stratifin (SFN) expression levels demonstrated an area under the receiver operating characteristic curve values of 0.84 for discriminating patients with PNI from NPNI patients. Moreover, EV SFN expression levels were an independent predictor of CRC prognosis. In this study, we identified SFN as a potential biomarker for the diagnosis of PNI in stage II CRC patients.
先前的研究表明，神经周围侵犯（PNI）的存在与结直肠癌（CRC）患者的预后显著较差相关。在本研究中，我们使用定量蛋白质组学对非神经周围侵犯（NPNI）和神经周围侵犯之间的细胞外囊泡（EV）多样性进行了详细分析，旨在研究结直肠癌中神经周围侵犯的潜在机制。定量蛋白质组学技术用于鉴定来自有和没有神经周围侵犯的CRC患者（分别为PNI和非PNI（NPNI）组）以及健康志愿者的血清纯化EV的蛋白质组。质谱数据通过ELISA和蛋白质印迹分析进行验证。PNI组血清EV的蛋白质组谱与NPNI组不同。来自PNI的血清衍生EV比来自NPNI组的EV促进更显著的细胞迁移。EV层粘连蛋白（SFN）表达水平在区分PNI患者和NPNI患者时的受试者工作特征曲线下面积值为0.84。此外，EV SFN表达水平是CRC预后的独立预测因子。在本研究中，我们将SFN鉴定为II期CRC患者中PNI诊断的潜在生物标志物。
