Britton Chance Center for Biomedical Photonics, Wuhan National Laboratory for Optoelectronics-Hubei Bioinformatics, Molecular Imaging Key Laboratory, Systems Biology Theme, Department of Biomedical Engineering, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan 430074, China.
Clinical laboratory, Tongji Hospital of Tongji Medical College, Huzhong University of Science and Technology (HUST), NO.1095 Jie Fang Avenue, Hankou, Wuhan 430030, China.
J Proteomics. 2018 Jun 15;181:225-237. doi: 10.1016/j.jprot.2018.04.026. Epub 2018 Apr 23.
Colorectal cancer (CRC) has become one of the most common cancers worldwide and the fifth most prevalent cancer in China with an upward trend in incidence rates. Altered glycosylation significantly affects the structural and functional changes in immunoglobulin G (IgG) and was consequently associated with disease progression. In this study, we explored the association of glycosylation with CRC prognosis through characterizing serum IgG N-glycans derived from individuals consisting of normal, benign colorectal and CRC cohorts in discovery set. Statistical analysis showed nine of IgG N-glycans were differentially expressed in disease groups compared with controls. Additionally, five out of them were still significantly changed in CRC patients at all tumor node metastasis (TNM) stages as compared with controls. Principal component analysis (PCA) indicated obvious differentiation of benign and cancer patients from normal individuals. Further diagnostic performance of receiver operator curve (ROC) analysis demonstrated at least moderately accurate area under the curve (AUC) score with preferable sensitivity and specificity, suggesting these five IgG N-glycans were probably correlated with CRC progression. Significantly, this result has been verified in validation set. Moreover, IgG N-glycosylation analysis suggested that core-fucosylation, sialylation and sialo core-fucosylation were possibly related to the development of CRC.
In-depth IgG N-glycome profiling of colorectal benign patients, colorectal cancer and normal individuals reveals differentially expression levels of N-glycosylation. Differing from serum comprehensive glycomes, profiling of specific serum glycoprotein contributes to more detailed understanding of biological relevance of glycosylation alterations in disease prognosis. Additionally, the high-throughput technique, MADLI-TOF-MS could absolutely relieve manual stress from sample preparation and accelerate information acquisition as compared to another recent analytical method. Moreover, we introduced a fast and easy data processing of MS exported files based on a software solution, which had the advantage of avoiding time consuming in manually searching and calculating the interesting peaks, and automatically producing the average percentage of each glycan over usual operation with Microsoft Excel. Besides, it may be useful for large-scale study.
结直肠癌（CRC）已成为全球最常见的癌症之一，也是中国第五大常见癌症，发病率呈上升趋势。糖基化的改变显著影响免疫球蛋白 G（IgG）的结构和功能变化，因此与疾病的进展有关。在这项研究中，我们通过在发现集中对由正常、良性结直肠和 CRC 队列组成的个体的血清 IgG N-糖链进行特征分析，探讨了糖基化与 CRC 预后的关系。统计分析显示，与对照组相比，疾病组中有 9 种 IgG N-糖链在表达上有差异。此外，与对照组相比，在所有肿瘤淋巴结转移（TNM）阶段的 CRC 患者中，其中 5 种仍有显著变化。主成分分析（PCA）表明良性和癌症患者与正常个体明显分化。进一步的接收器工作特征（ROC）分析诊断性能表明，曲线下面积（AUC）评分至少具有中等准确性，且具有较好的灵敏度和特异性，表明这 5 种 IgG N-糖链可能与 CRC 进展相关。值得注意的是，这一结果在验证集中得到了验证。此外，IgG N-糖基化分析表明，核心岩藻糖基化、唾液酸化和唾液酸化核心岩藻糖基化可能与 CRC 的发生有关。
对结直肠良性患者、结直肠癌和正常人的深入 IgG N-聚糖组谱分析揭示了 N-糖基化的差异表达水平。与血清综合糖谱不同，特定血清糖蛋白的分析有助于更详细地了解糖基化改变在疾病预后中的生物学相关性。此外，与另一种最近的分析方法相比，MADLI-TOF-MS 的高通量技术绝对可以减轻样品制备过程中的人为压力，并加速信息采集。此外，我们引入了一种基于软件解决方案的 MS 导出文件的快速简便的数据处理，该解决方案具有避免手动搜索和计算感兴趣峰以及自动生成每个聚糖在通常操作下的平均百分比的优点，而无需通常的 Microsoft Excel 操作。此外，它可能对大规模研究有用。
