title: A fourteen gene GBM prognostic signature identifies association of immune response pathway and mesenchymal subtype with high risk group.
abstract: BACKGROUND
  Recent research on glioblastoma (GBM) has focused on deducing gene signatures predicting prognosis. The present study evaluated the mRNA expression of selected genes and correlated with outcome to arrive at a prognostic gene signature.
  
  
  METHODS
  Patients with GBM (n = 123) were prospectively recruited, treated with a uniform protocol and followed up. Expression of 175 genes in GBM tissue was determined using qRT-PCR. A supervised principal component analysis followed by derivation of gene signature was performed. Independent validation of the signature was done using TCGA data. Gene Ontology and KEGG pathway analysis was carried out among patients from TCGA cohort.
  
  
  RESULTS
  A 14 gene signature was identified that predicted outcome in GBM. A weighted gene (WG) score was found to be an independent predictor of survival in multivariate analysis in the present cohort (HR = 2.507; B = 0.919; p<0.001) and in TCGA cohort. Risk stratification by standardized WG score classified patients into low and high risk predicting survival both in our cohort (p = <0.001) and TCGA cohort (p = 0.001). Pathway analysis using the most differentially regulated genes (n = 76) between the low and high risk groups revealed association of activated inflammatory/immune response pathways and mesenchymal subtype in the high risk group.
  
  
  CONCLUSIONS
  We have identified a 14 gene expression signature that can predict survival in GBM patients. A network analysis revealed activation of inflammatory response pathway specifically in high risk group. These findings may have implications in understanding of gliomagenesis, development of targeted therapies and selection of high risk cancer patients for alternate adjuvant therapies.
authors: Department of Neurosurgery, National Institute of Mental Health and Neuro Sciences, Bangalore, India.
authors: Arivazhagan
authors: A
authors: Arimappamagan
authors: Kumaravel
authors: K
authors: Somasundaram
authors: Kandavel
authors: K
authors: Thennarasu
authors: Sreekanthreddy
authors: S
authors: Peddagangannagari
authors: Harish
authors: H
authors: Srinivasan
authors: Bangalore C
authors: BC
authors: Shailaja
authors: Cini
authors: C
authors: Samuel
authors: Irene Rosita Pia
authors: IR
authors: Patric
authors: Sudhanshu
authors: S
authors: Shukla
authors: Balaram
authors: B
authors: Thota
authors: Krishnarao Venkatesh
authors: KV
authors: Prasanna
authors: Paritosh
authors: P
authors: Pandey
authors: Anandh
authors: A
authors: Balasubramaniam
authors: Vani
authors: V
authors: Santosh
authors: Bangalore Ashwathnarayanara
authors: BA
authors: Chandramouli
authors: Alangar Sathyaranjandas
authors: AS
authors: Hegde
authors: Paturu
authors: P
authors: Kondaiah
authors: Manchanahalli R
authors: MR
authors: Sathyanarayana Rao
mesh_terms: D019295:Computational Biology; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D053263:Gene Regulatory Networks; D005909:Glioblastoma / Q000235:genetics* / Q000276:immunology* / Q000378:metabolism / Q000401:mortality; D006801:Humans; D007249:Inflammation / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D058977:Molecular Sequence Annotation; D011379:Prognosis; D020543:Proteome; D015203:Reproducibility of Results; D012306:Risk; D015398:Signal Transduction; D059467:Transcriptome
chemical_list: D020543:Proteome
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