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MALDI-TOF Mass Spectrometric Analysis of Brain Tumor Cyst Fluid Reveals a Protein Peak Corresponding to ApoC1 and LuzP6

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Open Journal of Modern Neurosurgery 2018年第3期8卷 251-263页

作者： Mathias Groll Jochen Frenzel Matthias Krause anne schanzer Wolf Müller Klaus Eschrich Ulf Nestler Department of Neurosurgery University Hospital LeipzigLeipzigGermany Rudolf-Schonheimer-Institute of Biochemistry Medical FacultyUniversity of LeipzigLeipzigGermany Institute of Neuropathology Justus Liebig University GiessenGiessenGermany Institute of Neuropathology University Hospital LeipzigLeipzigGermany

Objectives: SELDI-TOF and MALDI-TOF mass spectrometry (MS) are laser desorption technologies that allow for proteomic examination of molecular masses in small amounts of samples. In a precedent study, the feasibility of SELDI-TOF MS assessment of proteins in cerebrospinal fluid and tumor cyst fluid had been shown. In the present study, we analyzed whether MALDI-TOF MS examination of these fluids leads to comparable results. Methods: During neurosurgical intervention, cyst fluids from 24 glioblastomas and 15 metastases were collected. As control, cerebrospinal fluid samples from 23 patients were obtained. The samples were prepared using a protocol optimized for MALDI-TOF MS. Mass spectra were recorded and peaks were extracted, characterized by masses and relative intensities. These peaks were analyzed for statistically significant differences between the diagnosis groups and compared to SELDI-TOF MS data. Results: 41 protein peaks known from the SELDI-TOF MS analysis could be confirmed by MALDI-TOF MS, and the cellular expression of the proteins LuzP6 and ApoC1, corresponding to the protein peaks 6433 and 6632, was shown immunohistochemically in glioblas-toma tissue. The MALDI-TOF spectrometry extends the range of analysis down to 1.4 kDa, whereas the upper detection limit lies below 23 kDa. Discussion: The presented proteomic approach yields an inventory of protein masses, found in the tumor cyst at the time of puncture. It does not reveal pathophysiologic, metabolic or secretory pathways that lead to the presence of proteins in the cyst. These have to be assessed immunohistochemically or on mRNA level in the surrounding tumor cells. Conclusion: MALDI-TOF MS of tumor cyst fluid discloses protein sizes, overexpressed or lost in tumor tissue. A thorough proteomic work-up is needed to identify the underlying proteins and metabolic pathways.

关键词： Cerebrospinal Fluid Cerebral Metastasis Glioblastoma Mass Spectrometry Tumor Cyst

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