数字农科院2.0

A novel photocleavable amino-modified graphene for covalent purification of N-glycans from hepatocellular carcinoma patients' serum for potential biomarkers discovery

文献类型： 外文期刊

作者： Chao, Xuyuan;Yang, Shengjie;Zhang, Baoying;Zang, Xin;Zhang, Jingyi;Liu, Xizi;Chen, Lu;Qi, Lu;Xue, Xiaofeng;Hu, Han;Wang, Xinghe

作者机构：

关键词： Photocleavable amino graphene;N-Glycans;Human serum;Hepatocellular carcinoma;Cancer biomarker;MALDI-TOF/TOF MS

期刊名称： CANCER NANOTECHNOLOGY

ISSN： 1868-6958

年卷期： 2025 年 16 卷 1 期

页码：

收录情况： SCIE（2025版）

摘要： Glycosylation alterations have emerged as significant indicators in the landscape of cancer diagnosis, with aberrant N-glycans standing out as potential biomarkers. The existing methods for purifying N-glycans mainly rely on their hydrophilicity, affinity, and size. These methods exhibit relatively weak binding forces and low specificity based on non-covalent interactions. Moreover, the current liquid chromatography-based N-glycan purification and detection techniques must be bettered for clinical settings' rapid diagnostic requirements. Here, we have developed a method involving the covalent binding of graphene modified with photocleavable amino groups to N-glycans in hepatocellular carcinoma (HCC) patients' serum glycoproteins. The N-glycans are identified using MALDI-TOF/TOF MS, catering to the requirements of biological research and the diagnosis of liver cancer disease. Specifically, amino-functionalized graphene is linked with photocleavable groups bearing hydrazide functional group, then undergoes acyl hydrazone covalent reaction with aldehyde groups on the side chains of oxidized monosaccharides to capture the N-glycans. Finally, under UV irradiation at a wavelength of 356 nm for 15 s, the ortho-nitrobenzyl photocleavable groups undergo cleavage, completing the release of captured N-glycans, which are then subjected to MALDI-TOF/TOF MS mass spectrometry for detection. Our findings demonstrate significant differences in the N-glycan profiles between serum samples of liver cancer patients and healthy individuals. These differences are characterized by increased abundance and molecular weight of N-glycans. Through biomarker screening, one N-glycan with an m/z ratio of 1847.01 shows the potential to serve as a diagnostic biomarker for liver cancer (P < 0.05). Our research underscores the potential of photocleavable amino-modified graphene for detecting aberrant N-glycans in HCC patients' serum to elucidate the intricate between aberrant N-glycan alterations and HCC. This research paves the way for developing novel biomarkers, diagnostic strategies, and therapeutic interventions to combat this complex disease.

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