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本研究通过分析胃癌患者血清N-糖图谱在癌变过程中的特征性改变,新建用于诊断胃癌N-糖标志物,并判断其诊断效力。收集胃癌(n=80)、胃溃疡(n=25)和健康对照(n=139)血清,基于DNA测序仪的毛细管电泳技术(DSA-FACE)检测每份血清标本中N-糖组图谱;采用临床免疫分析技术检测每份血清常规肿瘤标志物;分析N-糖图谱中特征性糖结构在疾病与对照组中的差异,及其在肿瘤进展过程中的改变,应用受试者工作曲线(ROC)衡量单个N-糖及常规肿瘤标志物诊断效力,Logistic逐步回归法建立有效的多指标诊断模型。每份血糖N-糖图谱至少得到9个N-糖结构峰。多个核心岩藻糖结构峰及侧支岩藻糖结构峰在三组有显著差异。在肿瘤组中,peak 5与peak 9在肿瘤组中显著升高,而含有核心岩藻糖结构的糖链peak 2、3、6、7和peak 8显著性降低,并且在胃癌进展期中,这类核心岩藻糖结构峰值随着肿瘤恶性程度的加重呈逐渐下降趋势。本研究所建立的N-糖诊断模型GCglycoB,在不影响特异度的情况下,较常规胃癌标志物联合应用敏感度提高20%,正确率提高26.7%。新建N-糖诊断标志物GCglycoB与现有肿瘤标志物比较,可显著提高胃癌诊断率;但这一新的胃癌诊断模型离理想标志物要求还存在一定距离,尚需临床大样本多中心补充、验证;胃癌核心岩藻糖结构降低机制仍待进一步研究。
In this study, by analyzing the characteristic changes of serum N-glycomapry in patients with gastric cancer during the course of carcinogenesis, this study was newly established to diagnose gastric cancer N-glycoprotein and to determine its diagnostic efficacy. The serum of gastric cancer (n = 80), gastric ulcer (n = 25) and healthy controls (n = 139) were collected and DNA samples were analyzed by capillary electrophoresis (DSA-FACE) ; Using routine immunoassay to detect routine serum tumor markers; analyzing the difference of characteristic glycostructure in N-glycan profile between disease and control group and its changes in tumor progression, using the working curves of subjects (ROC) to evaluate the diagnostic efficacy of single N-glycan and routine tumor markers, and to establish an effective multi-index diagnosis model by Logistic stepwise regression. Each glycemic N-glycan map gives at least 9 N-glycan peaks. Multiple core fucose structure peak and side branch fucose structure peak in the three groups were significantly different. In the tumor group, peak 5 and peak 9 were significantly increased in the tumor group, while the peak 2,3,6,7 and peak 8 of the sugar chain containing the core fucose structure were significantly decreased, and in the progression of gastric cancer, this The peak of core-like fucose structure decreased gradually with the increase of malignant degree. In our study, GCglycoB, a diagnostic model of N-glycans established by our study, showed a 20% increase in sensitivity and 26.7% accuracy compared with conventional gastric cancer markers without affecting the specificity. Compared with the existing tumor markers, GCglycoB, a new N-glycan diagnostic marker, can significantly improve the diagnosis rate of gastric cancer. However, this new gastric cancer diagnosis model still has a certain distance from the ideal marker, Validation; gastric core fucose structure reduction mechanism remains to be further studied.