Proteomics-based Identification of Serum Biomarkers : Role of Secreted MCSF and CRP in Glioma Pathogenesis
Mamatha, B N
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Gliomas are the neoplasia of glial cells present in the brain and comprises of more than 70% of all the neoplasms of the central nervous system. They consist of a family of primary brain tumors that are categorized based on the cell type of origin. Astrocytoma, a tumor of astrocytic glial cells has the highest frequency of occurrence as compared to other glioma types and often referred to as glioma. Based on the malignancy of the tumor,World Health Organization (WHO) has classified astrocytoma into Grade I/Pilocytic Astrocytoma (PA), Grade II/ Diffuse Astrocytoma (DA), Grade III/Anaplastic Astrocytoma (AA) and Grade IV/Glioblastoma (GBM). GBM is the most frequent and malignant primary brain tumor in adults. The standard treatment for GBM includes surgical resection of the tumor followed by radiation and temozolomide therapy. In spite of such mutlimodal treatment protocol followed, the median survival of the GBM remains as low as 15 months. While multiple markers with potential utility in diagnosis, prognosis and therapy of GBM have been reported based on profiling of gene expression, protein expression, miRNA and methylation pattern using tumor tissue, serum-based markers are scanty. Serum biomarkers have great potential in clinical decision making and management of glioma. Serum is an attractive source for biomarker mining since it can be obtained easily by less invasive method. Further, they have wide range of application which includes diagnosis, disease classification, prognosis, predicting risk and outcome of the disease. More importantly, serum can be obtained easily during follow-up of disease which could make it useful to detect tumor recurrence. This is particularly beneficial because glioma diagnosis and monitoring tumor recurrence are carried out by Magnetic Resonance Imaging (MRI) and Computed Tomography (CT) scan, which is time consuming and less cost effective. The current study was designed to identify serum biomarkers of glioma by using proteomic approaches and to understand the functional role of selected biomarkers in glioma pathogenesis. This study has been divided into three parts. In part I, we profiled cytokines using bead array method and by applying various statistical analyses we derived an 18-cytokine signature. In part II, Macrophage Colony Stimulating Factor (MCSF), one of the proteins elevated in GBM sera as identified by bead array method was investigated for its regulation and function in glioma. In part III, serum profiling by antibody microarray was performed and developed a serum based three-marker panel for distinguishing GBM from normal samples. Further, the role of C-Reactive Protein (CRP), a highest abundant serum protein in GBM, was investigated in detail.