Department of Neurological Surgery, Vanderbilt University Medical Center, Nashville, TN, USA.
Int J Oncol. 2012 Jun;40(6):1995-2003. doi: 10.3892/ijo.2012.1355. Epub 2012 Feb 3.
Analyzing molecular biomarkers using blood is an important approach for clinical assessment of malignant glioma. We investigated a molecular proteomic biomarker-based approach for glioblastoma using patients' blood samples. The expression levels of a list of candidate proteins were quantified in plasma and serum samples from two different cohorts of patients with malignant glioma and normal controls. The biological function was studied for one of the identified markers. Additionally, the prognostic significance of protein marker expression was measured by survival analysis. As a result, protein biomarkers associated with malignant glioma were identified from the blood specimens and five of the protein biomarkers were common to both cohorts. Immunohistochemical analysis demonstrated that many of the protein biomarkers identified in peripheral blood specimens were expressed in malignant gliomas. Staining levels for one of the biomarkers, MIP-1α, was found to correlate with WHO grade among invasive gliomas, and we demonstrate that MIP-1α promotes human glioblastoma cell proliferation and migration. Additionally, four prognostic protein biomarkers were identified. In conclusion, we demonstrate that both peripheral blood plasma and serum specimens are highly valuable and complementary to each other in the quest for protein biomarkers of malignant glioma. Sets of novel protein biomarkers were identified that may aid in the diagnosis and prognosis of patients with malignant glioma.
利用血液分析分子生物标志物是临床评估恶性神经胶质瘤的重要方法。我们研究了一种基于分子蛋白质组生物标志物的方法，用患者的血液样本检测胶质母细胞瘤。在来自两个不同的恶性神经胶质瘤患者队列和正常对照组的血浆和血清样本中，对一组候选蛋白的表达水平进行了定量分析。研究了一种鉴定出的标记物的生物学功能。此外，通过生存分析测量了蛋白质标志物表达的预后意义。结果，从血液标本中鉴定出与恶性神经胶质瘤相关的蛋白质生物标志物，其中 5 种蛋白质生物标志物在两个队列中均存在。免疫组织化学分析表明，在周围血液标本中鉴定出的许多蛋白质生物标志物在恶性神经胶质瘤中表达。一种生物标志物 MIP-1α 的染色水平与侵袭性神经胶质瘤中的 WHO 分级相关，我们证明 MIP-1α 促进人胶质母细胞瘤细胞的增殖和迁移。此外，还鉴定出了四个预后蛋白生物标志物。总之，我们证明了外周血血浆和血清标本在寻找恶性神经胶质瘤的蛋白质生物标志物方面都非常有价值且互为补充。鉴定出了一系列新的蛋白质生物标志物，它们可能有助于恶性神经胶质瘤患者的诊断和预后。
