title: An Eighteen Serum Cytokine Signature for Discriminating Glioma from Normal Healthy Individuals.
abstract: Glioblastomas (GBM) are largely incurable as they diffusely infiltrate adjacent brain tissues and are difficult to diagnose at early stages. Biomarkers derived from serum, which can be obtained by minimally invasive procedures, may help in early diagnosis, prognosis and treatment monitoring. To develop a serum cytokine signature, we profiled 48 cytokines in sera derived from normal healthy individuals (n = 26) and different grades of glioma patients (n = 194). We divided the normal and grade IV glioma/GBM serum samples randomly into equal sized training and test sets. In the training set, the Prediction Analysis for Microarrays (PAM) identified a panel of 18 cytokines that could discriminate GBM sera from normal sera with maximum accuracy (95.40%) and minimum error (4.60%). The 18-cytokine signature obtained in the training set discriminated GBM sera from normal sera in the test set as well (accuracy 96.55%; error 3.45%). Interestingly, the 18-cytokine signature also differentiated grade II/Diffuse Astrocytoma (DA) and grade III/Anaplastic Astrocytoma (AA) sera from normal sera very efficiently (DA vs. normal-accuracy 96.00%, error 4.00%; AA vs. normal-accuracy 95.83%, error 4.17%). Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis using 18 cytokines resulted in the enrichment of two pathways, cytokine-cytokine receptor interaction and JAK-STAT pathways with high significance. Thus our study identified an 18-cytokine signature for distinguishing glioma sera from normal healthy individual sera and also demonstrated the importance of their differential abundance in glioma biology.
authors.affiliation: Department of Microbiology and Cell Biology, Indian Institute of Science, Bangalore 560012, India.
authors.forename: Mamatha B
authors.initials: MB
authors.lastname: Nijaguna
authors.affiliation: Department of Microbiology and Cell Biology, Indian Institute of Science, Bangalore 560012, India.
authors.forename: Vikas
authors.initials: V
authors.lastname: Patil
authors.affiliation: Department of Neurosurgery, Sri Satya Sai Institute of Higher Medical Sciences, Bangalore 560066, India.
authors.forename: Alangar S
authors.initials: AS
authors.lastname: Hegde
authors.affiliation: Department of Neurosurgery, National Institute of Mental Health and Neuro Sciences, Bangalore 560029, India.
authors.forename: Bangalore A
authors.initials: BA
authors.lastname: Chandramouli
authors.affiliation: Department of Neurosurgery, National Institute of Mental Health and Neuro Sciences, Bangalore 560029, India.
authors.forename: Arimappamagan
authors.initials: A
authors.lastname: Arivazhagan
authors.affiliation: Department of Neuropathology, National Institute of Mental Health and Neuro Sciences, Bangalore 560029, India.
authors.forename: Vani
authors.initials: V
authors.lastname: Santosh
authors.affiliation: Department of Microbiology and Cell Biology, Indian Institute of Science, Bangalore 560012, India.
authors.forename: Kumaravel
authors.initials: K
authors.lastname: Somasundaram
mesh_terms: D000328:Adult; D001254:Astrocytoma / Q000097:blood / Q000175:diagnosis; D014408:Biomarkers, Tumor / Q000097:blood; D001921:Brain / Q000473:pathology; D001932:Brain Neoplasms / Q000097:blood* / Q000175:diagnosis*; D016207:Cytokines / Q000097:blood*; D005909:Glioblastoma / Q000097:blood / Q000175:diagnosis; D005910:Glioma / Q000097:blood* / Q000175:diagnosis*; D006801:Humans; D008875:Middle Aged; D060388:Support Vector Machine; D055815:Young Adult
chemical_list: D014408:Biomarkers, Tumor; D016207:Cytokines