Article
Identification of CSF peptide markers for glioblastoma multiforme using peptidomics screening technology
Peptidmarker für Glioblastoma multiforme im Liquor cerebrospinalis – Screening und Identifizierung mit Peptidomics
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Published: | April 23, 2004 |
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Outline
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Objective
To identify CSF peptide markers for non-invasive diagnosis of malignant gliomas, eventually targeting early detection of tumor recurrences, assessment of efficacy of adjuvant therapy and differential diagnosis versus metastasis or primary CNS lymphoma.
Methods
We used the Peptidomics technology Differential Peptide Display to screen CSF from 11 patients with glioblastoma multiforme (GBM) and of 13 controls undergoing myelography for degenerative spinal disorders. Several statistical parameters and tests (absolute difference, U-test, ROC Analysis, Youden’s test) were applied to select those peptide signals, which differed significantly between tumor and control. Selected peptides were identified by analysis of their amino acid sequence.
Results
Peptide maps depicted ~5000 peptide signals for each CSF sample. Eight peptides in CSF fulfilled all statistical selection criteria named above. Identification was possible in 5 of 8, which were fragments of osteopontin, albumin, transthyretin and alpha-1-antichymotrypsin.
Conclusions
Increased expression of osteopontin is known to be associated with GBM and angioneogenesis. The CSF presence of the other three peptides, which are cleavage products of abundant blood proteins, indicates a derangement of the blood-brain-barrier or a cross-over at the level of the blood-tumor barrier. Both mechanisms seem to be highly selective since other plasma peptides were not found elevated in CSF. Peptidomics is thus a powerful screening technique for the simultaneous screening of thousands of peptide signals in a single CSF sample followed by identification of marker candidates. Further targeted research is necessary to confirm sensitivity and specificity of the identified markers for GBM (versus other tumors) and to elucidate their value for the early assessment of recurrence or the efficacy of adjuvant therapy protocols.