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

Tumor cysts occur in a multitude of brain tumors. Since the cyst often forms a closed compartment, surrounded by tumor cells, proteomic analysis of the cyst fluid may help in describing pathophysiologic pathways, leading to cyst formation or tumor growth.

 The surface enhanced laser desorption ionisation mass spectrometry (SELDI-TOF MS), a highly sophisticated variant of matrix assisted laser desorption ionisation (MALDI-TOF MS), allows to assess directly cyst fluid protein content in as few as 2 microliters of specimen.

In the present study, the authors analyzed whether MALDI-TOF MS examination of these fluids led to comparable results. 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.

The findings showed that 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.

In conclusion, the presented proteomic approach yielded an inventory of protein masses, found in the tumor cyst at the time of puncture. However, it did not reveal pathophysiologic, metabolic or secretory pathways that led to the presence of proteins in the cyst. These have to be assessed immunohistochemically or on mRNA level in the surrounding tumor cells. And mass spectrometric analysis by laser-desorption ionization is a feasible tool to assess brain tumor cyst protein content in comparison to cerebrospinal fluid. A thorough work-up, including internet-based data research, immunohistochemistry and mRNA-analysis is needed to describe the obtained results in detail and to develop hypotheses concerning biomarkers.  

Article by Mathias Groll, et al, from Germany.

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