Heterogeneous Nuclear Ribonucleoproteins and Their Interactors Are a Major Class of Deregulated Proteins in Anaplastic Astrocytoma: A Grade III Malignant Glioma

Anaplastic
astrocytoma is a high grade malignant glioma (WHO grade
III) of the central nervous system which arises from a low grade II
tumor and invariably progresses into lethal glioblastoma (WHO grade
IV). We have studied differentially expressed proteins from the microsomal
fraction of the clinical specimens of these tumors, using iTRAQ and
high-resolution mass spectrometry followed by immunohistochemistry
for representative proteins on tissue sections. A total of 2642 proteins
were identified, 266 of them with minimum 2 peptide signatures and
2-fold change in expression. The major groups of proteins revealed
to be differentially expressed were associated with key cellular processes
such as post transcriptional processing, protein translation, and
acute phase response signaling. A distinct inclusion among these important
proteins is 10 heterogeneous nuclear ribonucleoproteins (hnRNPs) and
their interacting partners which have regulatory functions in the
cell. hnRNP-mediated post transcriptional events are known to play
a major role in mRNA processing, stability, and distribution. Their
altered levels have also been observed by us in lower (diffused astrocytoma)
and higher (glioblastoma) grades of gliomas, and membrane localization
of hnRNPs has also been documented in the literature. hnRNPs may thus
be major factors underlying global gene expression changes observed
in glial tumors while their differential presence in the microsomal
fraction suggests yet additional and unknown roles in tumorigenesis.