Investigation of serum proteome alterations in human glioblastoma multiforme.
Glioblastoma multiforme (GBM) or grade IV astrocytoma is the most common and lethal adult malignant brain tumor. The present study was conducted to investigate the alterations in the serum proteome in GBM patients compared to healthy controls. Comparative proteomic analysis was performed employing classical 2DE and 2D-DIGE combined with MALDI TOF/TOF MS and results were further validated through Western blotting and immunoturbidimetric assay. Comparison of the serum proteome of GBM and healthy subjects revealed 55 differentially expressed and statistically significant (p <0.05) protein spots. Among the identified proteins, haptoglobin, plasminogen precursor, apolipoprotein A-1 and M, and transthyretin are very significant due to their functional consequences in glioma tumor growth and migration, and could further be studied as glioma biomarkers and grade-specific protein signatures. Analysis of the lipoprotein pattern indicated elevated serum levels of cholesterol, triacylglycerol, and low-density lipoproteins in GBM patients. Functional pathway analysis was performed using multiple software including ingenuity pathway analysis (IPA), protein analysis through evolutionary relationships (PANTHER), database for annotation, visualization and integrated discovery (DAVID), and GeneSpring to investigate the biological context of the identified proteins, which revealed the association of candidate proteins in a few essential physiological pathways such as intrinsic prothrombin activation pathway, plasminogen activating cascade, coagulation system, glioma invasiveness signaling, and PI3K signaling in B lymphocytes. A subset of the differentially expressed proteins was applied to build statistical sample class prediction models for discrimination of GBM patients and healthy controls employing partial least squares discriminant analysis (PLS-DA) and other machine learning methods such as support vector machine (SVM), Decision Tree and Naïve Bayes, and excellent discrimination between GBM and control groups was accomplished.
Department of Biosciences and Bioengineering, Wadhwani Research Center for Biosciences and Bioengineering, Indian Institute of Technology Bombay, Powai, Mumbai, India.
Kishore
K
Gollapalli
Sandipan
S
Ray
Rajneesh
R
Srivastava
Durairaj
D
Renu
Prateek
P
Singh
Snigdha
S
Dhali
Jyoti
J
Bajpai Dikshit
Rapole
R
Srikanth
Aliasgar
A
Moiyadi
Sanjeeva
S
Srivastava
D001499:Bayes Theorem; D014408:Biomarkers, Tumor / Q000097:blood*; D001798:Blood Proteins / Q000032:analysis* / Q000378:metabolism; D016022:Case-Control Studies; D003663:Decision Trees; D015536:Down-Regulation; D015180:Electrophoresis, Gel, Two-Dimensional; D005909:Glioblastoma / Q000097:blood* / Q000378:metabolism; D006801:Humans; D015999:Multivariate Analysis; D010446:Peptide Fragments / Q000032:analysis; D060066:Protein Interaction Maps; D020543:Proteome / Q000032:analysis* / Q000378:metabolism; D040901:Proteomics / Q000379:methods; D015203:Reproducibility of Results; D015398:Signal Transduction; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D015854:Up-Regulation
D014408:Biomarkers, Tumor; D001798:Blood Proteins; D010446:Peptide Fragments; D020543:Proteome