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目的:解析乳腺癌组织的特异性糖链结构,为乳腺癌的早期诊断提供可能标志物。方法:收集2014年5月至2014年9月在陕西省肿瘤医院乳腺科手术切除的乳腺癌患者组织标本15例及距癌组织边缘3~5 cm的癌旁组织标本5例,另选取乳腺小叶增生组织标本4例,提取组织蛋白质,利用滤膜辅助的糖蛋白糖链释放方法获得N-连接糖链,应用基质辅助激光解析电离飞行时间质谱(MALDI-TOF/TOF-MS)技术分析乳腺癌组织、癌旁组织和正常乳腺组织中糖蛋白N-连接糖链类型分布和含量变化情况。结果:乳腺癌组织、癌旁组织和正常乳腺组织中分别鉴定到38、34和22个糖链。与癌旁组织及正常乳腺组织相比,癌症组织中复杂型、高甘露糖型、平分型、岩藻糖化和二天线型糖链的含量除高甘露糖型明显升高外,其他均显著降低(P<0.05或P<0.01)。乳腺癌组织中相对分子质量分别为1 580.455和1 742.490的2种高甘露糖型N-糖链的含量显著高于正常乳腺组织(P<0.05或P<0.01)、相对分子质量分别为1 647.473和1 850.583的2种复杂型N-糖链的含量则显著低于正常乳腺组织(P<0.05或P<0.01)。这4种糖链经ROC曲线分析显示具有较高检测准确性(P<0.05或P<0.01)。结论:发现的4种乳腺癌组织特异性的N-糖链有成为早期诊断和靶向治疗标志物的潜力。
Objective: To analyze the structure of specific sugar chains in breast cancer and provide a possible marker for the early diagnosis of breast cancer. Methods: Fifteen cases of breast cancer patients underwent surgical resection of breast cancer in Shaanxi Provincial Tumor Hospital from May 2014 to September 2014 and 5 cases of paracancerous tissues 3 to 5 cm away from the edge of cancer tissue. In 4 cases of hyperplastic tissue samples, tissue proteins were extracted and N-linked sugar chains were obtained by membrane glycoprotein sugar chain release. MALDI-TOF-TOF-MS was used to analyze breast cancer Tissue, paracancerous tissues and normal breast tissue glycoprotein N-linked sugar chain type distribution and content changes. Results: 38, 34 and 22 sugar chains were identified in breast cancer tissues, paracancerous tissues and normal breast tissues respectively. Compared with the adjacent tissues and normal breast tissue, the content of complex type, high mannose type, bisection type, fucosylation and two-day linear sugar chain in cancer tissues were significantly higher than those in high-mannose type Decreased (P <0.05 or P <0.01). The content of two high-mannose N-glycans with relative molecular mass of 1 580.455 and 1 742.490 in breast cancer tissues was significantly higher than that in normal breast tissues (P <0.05 or P <0.01), and the relative molecular weights were 1 647.473 And 2 kinds of complex N-glycans of 1 850.583 were significantly lower than that of normal breast tissues (P <0.05 or P <0.01). The four sugar chains showed high detection accuracy (R <0.05 or P <0.01) by ROC curve analysis. CONCLUSIONS: The four N-glycans found in breast cancer tissues have the potential to be useful markers for early diagnosis and targeted therapy.