Zhao Qianqian, Zhan Tiancheng, Deng Zaian, Li Qianqian, Liu Yaming, Yang Shaojie, Ji Dengbo, Li Yan
1Laboratory of Interdisciplinary Research, Institute of Biophysics, Chinese Academy of Sciences, 15 Datun Road, Chaoyang District, Beijing, 100101 China.
2University of Chinese Academy of Sciences, Beijing, 100049 China.
Clin Proteomics. 2018 Mar 2;15:9. doi: 10.1186/s12014-018-9182-4. eCollection 2018.
Carcinoembryonic antigen (CEA) is a glycoprotein associated with colorectal cancer (CRC). While the functions of its gene and protein have been fully characterized, its post-translational modifications in the context of CRC development remain undefined.
To show the correlation between the different stages of CRC development and changes in the glycosylation patterns of CEA, we analyzed CEA in tumor tissues (CEA-T) and paired tumor-adjacent normal tissues (CEA-A) from 53 colorectal cancer patients using a high-density lectin microarray containing 56 plant lectins.
We detected higher expression levels of fucose, mannose and Thomsen-Friedenreich antigen, and lower expression levels of -acetylgalactosamine, -acetylglucosamine, galactose, branched and bisecting -glycans on CEA in the tumor tissues relative to the tumor-adjacent normal tissues. Furthermore, a combinatorial assessment of 9 lectins is sufficient to distinguish CRC tumor tissues from tumor-adjacent normal tissues with 83% sensitivity and ~ 90% specificity. Moreover, the levels of -acetylgalactosamine, mannose, galactose, -acetylglucosamine on CEA showed a downward trend after first experiencing an increase at Stage II with the stages of CRC.
Our insights into the changing CEA glycosylation patterns and their role in the development of CRC highlight the importance of glycan variants on CEA for early clinical detection and staging of CRC.
癌胚抗原（CEA）是一种与结直肠癌（CRC）相关的糖蛋白。虽然其基因和蛋白质的功能已得到充分表征，但其在结直肠癌发生发展过程中的翻译后修饰仍不明确。
为了揭示结直肠癌不同发展阶段与CEA糖基化模式变化之间的相关性，我们使用包含56种植物凝集素的高密度凝集素微阵列，分析了53例结直肠癌患者肿瘤组织（CEA-T）和配对的肿瘤旁正常组织（CEA-A）中的CEA。
相对于肿瘤旁正常组织，我们在肿瘤组织中检测到CEA上岩藻糖、甘露糖和Thomsen-Friedenreich抗原的表达水平较高，而N-乙酰半乳糖胺、N-乙酰葡糖胺、半乳糖、分支和二分β-聚糖的表达水平较低。此外，对9种凝集素的组合评估足以区分结直肠癌肿瘤组织和肿瘤旁正常组织，灵敏度为83%，特异性约为90%。此外，随着结直肠癌分期的增加，CEA上N-乙酰半乳糖胺、甘露糖、半乳糖、N-乙酰葡糖胺的水平在II期先升高后呈下降趋势。
我们对CEA糖基化模式变化及其在结直肠癌发生发展中作用的深入了解，突出了CEA上聚糖变体在结直肠癌早期临床检测和分期中的重要性。
