Targeted Tissue Proteomic Analysis of Human Astrocytomas

Complicating proteomic analysis of whole tissues is the
obvious
problem of cell heterogeneity in tissues, which often results in misleading
or confusing molecular findings. Thus, the coupling of tissue microdissection
for tumor cell enrichment with capillary isotachophoresis-based selective
analyte concentration not only serves as a synergistic strategy to
characterize low abundance proteins, but it can also be employed to
conduct comparative proteomic studies of human astrocytomas. A set
of fresh frozen brain biopsies were selectively microdissected to
provide an enriched, high quality, and reproducible sample of tumor
cells. Despite sharing many common proteins, there are significant
differences in the protein expression level among different grades
of astrocytomas. A large number of proteins, such as plasma membrane
proteins EGFR and Erbb2, are up-regulated in glioblastoma. Besides
facilitating the prioritization of follow-on biomarker selection and
validation, comparative proteomics involving measurements in changes
of pathways are expected to reveal the molecular relationships among
different pathological grades of gliomas and potential molecular mechanisms
that drive gliomagenesis.