Laboratory of Molecular Neurooncology, Neuroscience Institute, Lithuanian University of Health Sciences, Eiveniu str. 4, LT50161 Kaunas, Lithuania.
Laser Research Centre (VU LRC), Vilnius University, Sauletekio Ave 10, LT10223 Vilnius, Lithuania.
Cells. 2019 Dec 19;9(1):16. doi: 10.3390/cells9010016.
High-grade astrocytomas are some of the most common and aggressive brain cancers, whose signs and symptoms are initially non-specific. Up to the present date, there are no diagnostic tools to observe the early onset of the disease. Here, we analyzed the combination of blood serum proteins, which may play key roles in the tumorigenesis and the progression of glial tumors. Fifty-nine astrocytoma patients and 43 control serums were analyzed using Custom Human Protein Antibody Arrays, including ten targets: ANGPT1, AREG, IGF1, IP10, MMP2, NCAM1, OPN, PAI1, TGFβ1, and TIMP1. The decision tree analysis indicates that serums ANGPT1, TIMP1, IP10, and TGFβ1 are promising combinations of targets for glioma diagnostic applications. The accuracy of the decision tree algorithm was 73.5% (75/102), which correctly classified 79.7% (47/59) astrocytomas and 65.1% (28/43) healthy controls. The analysis revealed that the relative value of osteopontin (OPN) protein level alone predicted the 12-month survival of glioblastoma (GBM) patients with the specificity of 84%, while the inclusion of the IP10 protein increased model predictability to 92.3%. In conclusion, the serum protein profiles of ANGPT1, TIMP1, IP10, and TGFβ1 were associated with the presence of astrocytoma independent of its malignancy grade, while OPN and IP10 were associated with GBM patient survival.
高级别星形细胞瘤是最常见和侵袭性最强的脑癌之一，其症状最初是非特异性的。截至目前，还没有诊断工具可以观察到疾病的早期发作。在这里，我们分析了血清蛋白的组合，这些蛋白可能在神经胶质瘤的发生和发展中起关键作用。使用定制的人类蛋白质抗体阵列分析了 59 名星形细胞瘤患者和 43 名对照血清，包括 10 个靶标：ANGPT1、AREG、IGF1、IP10、MMP2、NCAM1、OPN、PAI1、TGFβ1 和 TIMP1。决策树分析表明，血清 ANGPT1、TIMP1、IP10 和 TGFβ1 是胶质细胞瘤诊断应用的有前途的靶标组合。决策树算法的准确率为 73.5%（75/102），正确分类了 79.7%（47/59）的星形细胞瘤和 65.1%（28/43）的健康对照者。分析表明，骨桥蛋白（OPN）蛋白水平的相对值单独预测胶质母细胞瘤（GBM）患者的 12 个月生存率，特异性为 84%，而包含 IP10 蛋白可将模型预测能力提高到 92.3%。总之，ANGPT1、TIMP1、IP10 和 TGFβ1 的血清蛋白谱与星形细胞瘤的存在相关，而与恶性程度无关，而 OPN 和 IP10 与 GBM 患者的生存相关。
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