基于凝集素探针的高危II期结直肠癌患者的特异性判别技术

Colorectal cancer (CRC) has become one of the most serious malignant tumors threatening the life and health of the people in our country. Although stage II is an early stage of CRC, 20%-30% of these patients would have a recurrence, metastasis and even life-threatening after a standardized surgical operation. Currently, there is a lack of comprehensive and accurate identification of these high-risk stage II patients. Glycan is a sensitive and precise terminal metabolic signal. In this project, we will focus on the disease specific glycan changes. We will develop specific lectin probes as well as specific glycoisoforms of serum CEA to assess the risk of recurrence and metastasis in stage II CRC patients based on the technologies of micro tissue glycome mapping using lectin microarray. We will establish a new method for specific identification of high-risk stage II CRC patients by combining these glycobiomarkers with clinical pathological indexes and microsatellite instability detection. We hope this method could improve the accuracy of the existing diagnostic methods, and provide a theoretical basis for individualized treatment of CRC patients.

结直肠癌（colorectal cancer, CRC）已成为严重威胁我国人民生命健康的恶性肿瘤之一。II期CRC虽然是早中期，但有20%-30%的高危患者在手术治疗后会出现复发、转移甚至危及生命。目前临床尚缺乏能全面精确的甄别出这些高危患者的判别方法。糖链是一种灵敏、精细的末端代谢信号，本项目以疾病相关糖链变化为研究窗口，运用基于凝集素芯片的微量组织糖谱检测技术，开发评估II期CRC患者复发转移风险的特异性凝集素探针及血清CEA糖链异质体指标，联合临床病理指标及微卫星不稳定性（MSI）检测，建立对高危II期CRC患者进行特异性判别的新方法，补充并提高现有临床诊断技术的准确性，为CRC患者的个体化治疗提供理论依据。

结直肠癌（colorectal cancer, CRC）发病率和死亡率近年在我国呈显著上升趋势，已成为严重危害我国人民生命健康的恶性肿瘤之一。II期CRC虽然是早中期，但有20%-30%的高危患者在手术治疗后会出现复发、转移甚至危及生命。目前临床尚缺乏能全面精确的甄别出这些高危患者的判别方法。因此，寻找新型诊断指标，提高现有临床甄别高危II期CRC患者的准确率，成为提升CRC患者预后的迫切需求。.糖链是一种灵敏、精细的末端代谢信号。本项目针对II期CRC高危患者临床指征不明的问题，以疾病相关糖链变化为研究窗口，首先优化建立基于凝集素芯片和激光显微切割的CRC微量组织糖谱检测技术，在此基础上发现了表征II期CRC预后的特异性凝集素探针PHA-E。进一步，利用凝集素富集结合质谱检测等糖蛋白组学手段，在II期CRC患者肿瘤组织中发现平分型N-糖基化修饰的CEA糖链异质体与其预后密切相关，建立了联合凝集素探针PHA-E以及临床指标CEA的高危II期CRC预警新指标，为提高现有临床诊断技术和精准个体化治疗提供依据。.此外，我们将建立的基于凝集素探针的疾病糖链标志物研究策略推广至肺癌糖链生物标志物研究中。开发了利用5种特征性凝集素探针检测具有唾液酸修饰以及高甘露糖修饰的IgG糖链异质体，该指标能够作为一种新的无创指标，协助CT检查提高术前对早期恶性肺癌的检测准确率，进一步为开发基于凝集素探针的疾病糖链标志物研究提供实例。