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Published on: January 9, 2019
Identification of the Transmembrane Glucose Regulated Protein 78 as a Biomarker for the Brain Cancer Glioblastoma
H N Banerjee1, G Hyman2, S Evans2
1Department of Natural Science, Elizabeth City State University, Elizabeth City, NC, USA ; Department of Pharmaceutical Sciences, Elizabeth City State University, Elizabeth City, NC, USA.
Abstract:
The prognosis of patients with Glioblastoma Multiforme (GBM), the most malignant adult glial brain tumor, remains poor in spite of advances in treatment procedures, including surgical resection, irradiation and chemotherapy. Genetic heterogeneity of GBM warrants extensive studies to gain a thorough understanding of the biology of this tumor. While there have been several studies of global transcript profiling of glioma with the identification of gene signatures for diagnosis and disease management, translation into clinics is yet to happen. In the present study, we report a novel proteomic approach by using two-dimensional difference gel electrophoresis (2D-DIGE) followed by spot picking and analysis of proteins/peptides by Mass Spectrometry. We report Glucose Regulated Protein 78 (GRP78) as a differentially expressed protein in the GBM cell line compared to human normal Astrocyte cells. In addition to proteomic studies, we performed microarray analysis which further confirmed up regulation of GRP78 in GBM cells compared to human normal Astrocyte cells. GRP78 has long been recognized as a molecular chaperone in the endoplasmic reticulum (ER) and can be induced by the ER stress response. Besides its location in the ER, GRP78 has been found in cell plasma membrane, cytoplasm, mitochondria, nucleus and other cellular secretions. GRP78 is implicated in tumor cell proliferation, apoptosis resistance, immune escape, metastasis and angiogenesis, and its elevated expression usually correlates with a variety of tumor micro environmental stresses, including hypoxia, glucose deprivation, lactic acidosis and inflammatory response. GRP78 protein acts as a centrally located sensor of stress, which senses and facilitates the adaptation to the tumor microenvironment. Our findings showed differential expression of this gene in brain cancer GBM and thus confirm similarities in findings in existing transcriptional and translational studies. Thus, these findings could be of further importance for diagnostic, therapeutic and prognostic approaches for dealing with this highly malignant cancer.
Insights
This study identifies Glucose Regulated Protein 78 (GRP78) as a key protein in Glioblastoma Multiforme (GBM). Elevated GRP78 in GBM cells suggests potential new diagnostic and therapeutic targets for this aggressive brain cancer.
Area of Science:
- Oncology
- Proteomics
- Molecular Biology
Background:
- Glioblastoma Multiforme (GBM) is an aggressive adult brain tumor with a poor prognosis despite current treatments.
- Understanding GBM's genetic heterogeneity is crucial for developing effective therapies.
- Existing transcript profiling studies have identified gene signatures but lacked clinical translation.
Purpose of the Study:
- To investigate differential protein expression in GBM using a novel proteomic approach.
- To identify potential biomarkers for GBM diagnosis and treatment.
- To validate proteomic findings with transcriptomic data.
Main Methods:
- Utilized two-dimensional difference gel electrophoresis (2D-DIGE) for proteomic analysis.
- Employed Mass Spectrometry for protein/peptide identification.
- Performed microarray analysis to confirm gene expression levels.
Main Results:
- Identified Glucose Regulated Protein 78 (GRP78) as a differentially expressed protein in GBM cells compared to normal astrocytes.
- Confirmed the upregulation of GRP78 in GBM cells through microarray analysis.
- GRP78 is implicated in tumor proliferation, apoptosis resistance, immune escape, metastasis, and angiogenesis.
Conclusions:
- The study highlights GRP78 as a significant protein in GBM pathogenesis.
- Findings support similarities between transcriptional and translational studies in GBM.
- Elevated GRP78 presents potential diagnostic, therapeutic, and prognostic implications for GBM patients.
