Abstract
Diffuse astrocytoma (DA; WHO grade II) is a low-grade, primary brain neoplasm with high potential of recurrence as higher grade malignant form. We have analyzed differentially expressed membrane proteins from these tumors, using high-resolution mass spectrometry. A total of 2803 proteins were identified, 340 of them differentially expressed with minimum of 2 fold change and based on ≥2 unique peptides. Bioinformatics analysis of this dataset also revealed important molecular networks and pathways relevant to tumorigenesis, mTOR signaling pathway being a major pathway identified. Comparison of 340 differentially expressed proteins with the transcript data from Grade II diffuse astrocytomas reported earlier, revealed about 190 of the proteins correlate in their trends in expression. Considering progressive and recurrent nature of these tumors, we have mapped the differentially expressed proteins for their secretory potential, integrated the resulting list with similar list of proteins from anaplastic astrocytoma (WHO Grade III) tumors and provide a panel of proteins along with their proteotypic peptides, as a resource that would be useful for investigation as circulatory plasma markers for post-treatment surveillance of DA patients.
Highlights
Diffuse astrocytoma (DA; WHO grade II) is a low-grade, primary brain neoplasm with high potential of recurrence as higher grade malignant form
The expression level of four of the select proteins, epidermal growth factor receptor (EGFR), brevican core protein (BCAN), ectonucleotide pyrophosphatase/phosphodiesterase family member 6 (ENPP6) and heterogeneous nuclear ribonucleoprotein (HNRNP) K were studied by immunohistochemistry using commercially available Tissue microarray containing 13 Diffuse Astrocytomas cases and 4 control tissue cores (US BioMax)
Considering low incidence of these tumors and sample paucity, our experimental approach has been to carry out quantitative LC-MS/MS analysis using iTRAQ, on microsomal fraction purified from pooled tissue biopsies from patients diagnosed with DA, followed by cross-comparison with transcript data from individual patient samples and/or verification of the functionally significant members by immunohistochemistry on tissue microarrays with individual samples
Summary
Diffuse astrocytoma (DA; WHO grade II) is a low-grade, primary brain neoplasm with high potential of recurrence as higher grade malignant form. We have analyzed protein expression changes in the microsomal fraction of clinical tissue samples with diffuse astrocytoma in comparison to control, using iTRAQ and high-resolution mass spectrometry, followed by extensive bioinformatics analysis to get further insights into molecular changes in these tumors and to generate a resource which could be useful for developing circulatory biomarkers for clinical applications such as post-treatment surveillance.
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