Proteomic Analysis of the Low Molecular Mass Fraction of Newly Diagnosed and Recurrent Glioblastoma CUSA Fluid: A Pilot Investigation of the Peptidomic Profile

Glioblastoma multiforme (GBM) is a highly aggressive, treatment-resistant grade IV brain tumor with poor prognosis that grows rapidly and invades surrounding tissues, complicating surgery and frequently recurring. Although the crucial role of endogenous peptides has been highlighted for several tumors, the specific peptidomic profile of GBM remains unexplored to date. This study aimed to perform a preliminary characterization of the low molecular mass proteome fraction of Cavitron Ultrasonic Surgical Aspirator (CUSA) fluid collected from different tumor zones, i.e., the core and tumor periphery of newly diagnosed (ND) and recurrent (R) GBM. The samples, pooled by tumor type and collection zone, were centrifuged through molecular cut-off filter devices to collect the non-retained fraction of the proteome <10 kDa for direct full-length LC-MS analysis. A total of 40 and 24 peptides, fragments of 32 and 18 proteins, were marked as ND and R GBM COREs, respectively, while 132 peptides, fragments of 46 precursor proteins, were identified as common and included proteins which were cancer-related or involved in GBM pathophysiology. Besides providing a preliminary overview of the unexplored peptidome of GBM, this pilot study confirms peptidomics as a promising tool to discover potential GBM biomarkers in the perspective of clinical applications increasingly oriented towards a precision medicine approach. Data are available via ProteomeXchange with the identifier PXD060807.