title: Novel glioblastoma markers with diagnostic and prognostic value identified through transcriptome analysis.
abstract: OBJECTIVE
  Current methods of classification of astrocytoma based on histopathologic methods are often subjective and less accurate. Although patients with glioblastoma have grave prognosis, significant variability in patient outcome is observed. Therefore, the aim of this study was to identify glioblastoma diagnostic and prognostic markers through microarray analysis.
  
  
  METHODS
  We carried out transcriptome analysis of 25 diffusely infiltrating astrocytoma samples [WHO grade II--diffuse astrocytoma, grade III--anaplastic astrocytoma, and grade IV--glioblastoma (GBM)] using cDNA microarrays containing 18,981 genes. Several of the markers identified were also validated by real-time reverse transcription quantitative PCR and immunohistochemical analysis on an independent set of tumor samples (n = 100). Survival analysis was carried out for two markers on another independent set of retrospective cases (n = 51).
  
  
  RESULTS
  We identified several differentially regulated grade-specific genes. Independent validation by real-time reverse transcription quantitative PCR analysis found growth arrest and DNA-damage-inducible alpha (GADD45alpha) and follistatin-like 1 (FSTL1) to be up-regulated in most GBMs (both primary and secondary), whereas superoxide dismutase 2 and adipocyte enhancer binding protein 1 were up-regulated in the majority of primary GBM. Further, identification of the grade-specific expression of GADD45alpha and FSTL1 by immunohistochemical staining reinforced our findings. Analysis of retrospective GBM cases with known survival data revealed that cytoplasmic overexpression of GADD45alpha conferred better survival while the coexpression of FSTL1 with p53 was associated with poor survival.
  
  
  CONCLUSIONS
  Our study reveals that GADD45alpha and FSTLI are GBM-specific whereas superoxide dismutase 2 and adipocyte enhancer binding protein 1 are primary GBM-specific diagnostic markers. Whereas GADD45alpha overexpression confers a favorable prognosis, FSTL1 overexpression is a hallmark of poor prognosis in GBM patients.
authors.affiliation: Department of Molecular Reproduction, Indian Institute of Science, Bangalore, Karnataka, India.
authors.forename: Sreekanth P
authors.initials: SP
authors.lastname: Reddy
authors.forename: Ramona
authors.initials: R
authors.lastname: Britto
authors.forename: Katyayni
authors.initials: K
authors.lastname: Vinnakota
authors.forename: Hebbar
authors.initials: H
authors.lastname: Aparna
authors.forename: Hari Kishore
authors.initials: HK
authors.lastname: Sreepathi
authors.forename: Balaram
authors.initials: B
authors.lastname: Thota
authors.forename: Arpana
authors.initials: A
authors.lastname: Kumari
authors.forename: B M
authors.initials: BM
authors.lastname: Shilpa
authors.forename: M
authors.initials: M
authors.lastname: Vrinda
authors.forename: Srikantha
authors.initials: S
authors.lastname: Umesh
authors.forename: Cini
authors.initials: C
authors.lastname: Samuel
authors.forename: Mitesh
authors.initials: M
authors.lastname: Shetty
authors.forename: Ashwani
authors.initials: A
authors.lastname: Tandon
authors.forename: Paritosh
authors.initials: P
authors.lastname: Pandey
authors.forename: Sridevi
authors.initials: S
authors.lastname: Hegde
authors.forename: A S
authors.initials: AS
authors.lastname: Hegde
authors.forename: Anandh
authors.initials: A
authors.lastname: Balasubramaniam
authors.forename: B A
authors.initials: BA
authors.lastname: Chandramouli
authors.forename: Vani
authors.initials: V
authors.lastname: Santosh
authors.forename: Paturu
authors.initials: P
authors.lastname: Kondaiah
authors.forename: Kumaravel
authors.initials: K
authors.lastname: Somasundaram
authors.forename: M R Satyanarayana
authors.initials: MR
authors.lastname: Rao
mesh_terms: D014408:Biomarkers, Tumor / Q000235:genetics*; D001932:Brain Neoplasms / Q000175:diagnosis* / Q000235:genetics* / Q000401:mortality; D020869:Gene Expression Profiling; D005909:Glioblastoma / Q000175:diagnosis* / Q000235:genetics* / Q000401:mortality; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D020411:Oligonucleotide Array Sequence Analysis; D011379:Prognosis; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D014408:Biomarkers, Tumor