Abstract
Glioblastoma multiforme (GBM), the most malignant of all gliomas is characterized by a high degree of heterogeneity and poor response to treatment. The sub-ventricular zone (SVZ) is the major site of neurogenesis in the brain and is rich in neural stem cells. Based on the proximity of the GBM tumors to the SVZ, the tumors can be further classified into SVZ+ and SVZ−. The tumors located in close contact with the SVZ are classified as SVZ+, while the tumors located distantly from the SVZ are classified as SVZ−. To gain an insight into the increased aggressiveness of SVZ+ over SVZ− tumors, we have used proteomics techniques like 2D-DIGE and LC-MS/MS to investigate any possible proteomic differences between the two subtypes. Serum proteomic analysis revealed significant alterations of various acute phase proteins and lipid carrying proteins, while tissue proteomic analysis revealed significant alterations in cytoskeletal, lipid binding, chaperone and cell cycle regulating proteins, which are already known to be associated with disease pathobiology. These findings provide cues to molecular basis behind increased aggressiveness of SVZ+ GBM tumors over SVZ− GBM tumors and plausible therapeutic targets to improve treatment modalities for these highly invasive tumors.
Highlights
Glioblastoma Multiforme (GBM) is a malignant brain tumor, characterized by heterogeneity within the tumor and poor response to treatment[1]
Till date there has been no report of any study involving two different sub-groups of Glioblastoma multiforme (GBM) based on sub-ventricular zone (SVZ) involvement
Tumor proximity to the subventricular zone has been recently reported to play a significant role in the survival of GBM patients, where patients with tumors in SVZ contact had an overall survival period less than those with tumors distantly located to SVZ9
Summary
Glioblastoma Multiforme (GBM) is a malignant brain tumor, characterized by heterogeneity within the tumor and poor response to treatment[1]. It is the most aggressive of all known gliomas with patients having a survival period lower than one year from the time of diagnosis in most cases[2]. Progenitor astrocytes that go on to form glial cells colonize the subventricular zone (SVZ), the largest germinal zone in the brain found along the lateral walls of the lateral ventricles[4] This zone of the brain has been extensively studied as a site of neurogenesis[5] and is responsible for the development of neurons in an adult. We have performed a comprehensive serum and tissue proteome analysis of two sub-populations of GBMs to explore if SVZ involvement had any direct influence on tumor aggressiveness
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