Shionogi Innovation Center for Drug Discovery, Shionogi & Co., Ltd., Kita-21 Nishi-11 Kita-ku, Sapporo, Japan.
Translational Research Unit, Shionogi & Co., Ltd., 3-1-1 Futaba-cho, Toyonaka, Japan.
Glycoconj J. 2018 Oct;35(5):467-476. doi: 10.1007/s10719-018-9838-3. Epub 2018 Sep 8.
Hepatocellular carcinoma (HCC) is the major subtype of primary liver cancer, and is typically diagnosed late in its course. Considering the limitations and the reluctance of patients to undergo a liver biopsy, a reliable, noninvasive diagnostic marker that predicts and assesses the treatment and prognosis of HCC is needed. With recent technological advances of mass spectrometry, glycomics is gathering momentum and holds substantial potential to discover new glycan markers in cancer research. Here, to discover specific glycan markers for the early diagnosis of HCC, we analyzed the glycan profiles of gel-separated serum proteins of progressive liver disease model mice. By focused protein glycomics of 12 gel-separated glycoproteins using sera from the mouse models, we revealed the entire profile of glycans in each major serum protein. We found that the levels of trisialylated triantennary glycans of haptoglobin and vitamin D-binding protein increased significantly as the disease progressed, while the alteration in these protein levels were modest. Furthermore, these glycan increases were not observed in age-matched control mice. In conclusion, our approach has identified specific glycan marker candidates for the early diagnosis of HCC.
肝细胞癌（HCC）是原发性肝癌的主要亚型，通常在病程晚期被诊断出来。考虑到肝活检的局限性和患者的不情愿，我们需要一种可靠的、非侵入性的诊断标志物，以预测和评估 HCC 的治疗和预后。随着质谱技术的最新进展，糖组学正在兴起，并在癌症研究中发现新的聚糖标志物方面具有巨大潜力。在这里，为了发现用于 HCC 早期诊断的特定聚糖标志物，我们分析了进行性肝病模型小鼠凝胶分离血清蛋白的聚糖图谱。通过使用来自小鼠模型的血清对 12 种凝胶分离糖蛋白进行重点蛋白质糖组学分析，我们揭示了每种主要血清蛋白中聚糖的完整图谱。我们发现，随着疾病的进展，结合珠蛋白和维生素 D 结合蛋白的三唾液酸化三触角聚糖的水平显著增加，而这些蛋白水平的变化则不大。此外，在年龄匹配的对照小鼠中未观察到这些糖的增加。总之，我们的方法已经确定了用于 HCC 早期诊断的特定聚糖标志物候选物。
