title: FGF2 as a potential prognostic biomarker for proneural glioma patients.
abstract: BACKGROUND
  The survival of high-grade glioma patients is poor and the treatment of these patients can cause severe side effects. This fosters the necessity to identify prognostic biomarkers, in order to optimize treatment and diminish unnecessary suffering of patients. The aim of this study was to identify prognostic biomarkers for high-grade glioma patients.
  
  
  METHODS
  Eleven proteins were selected for analysis due to their suggested importance for survival of patients with other types of cancers and due to a high variation in protein levels between glioma patients (according to the Human Protein Atlas, www.proteinatlas.org). Protein expression patterns of these 11 proteins were analyzed by immunohistochemistry in tumor samples from 97 high-grade glioma patients. The prognostic values of the proteins were analyzed with univariate and multivariate Cox regression analyses for the high-grade glioma patients, including subgroup analyses of histological subtypes and immunohistochemically defined molecular subtypes.
  
  
  RESULTS
  The proteins with the most significant (univariate and multivariate p<0.05) correlations were analyzed further with cross-validated Kaplan-Meier analyses for the possibility of predicting survival based on the protein expression pattern of the corresponding candidate. Random Forest classification with variable subset selection was used to analyze if a protein signature consisting of any combination of the 11 proteins could predict survival for the high-grade glioma patients and the subgroup with glioblastoma patients. The proteins which correlated most significantly (univariate and multivariate p<0.05) to survival in the Cox regression analyses were Myc for all high-grade gliomas and FGF2, CA9 and CD44 for the subgroup of proneural gliomas, with FGF2 having a strong negative predictive value for survival. No prognostic signature of the proteins could be found.
  
  
  CONCLUSIONS
  FGF2 is a potential prognostic biomarker for proneural glioma patients, and warrants further investigation.
authors.affiliation: Department of Radiology, Oncology and Radiation Sciences, Section of Oncology, Rudbeck Laboratory , Uppsala , Sweden.
authors.forename: Linda
authors.initials: L
authors.lastname: Sooman
authors.forename: Eva
authors.initials: E
authors.lastname: Freyhult
authors.forename: Archita
authors.initials: A
authors.lastname: Jaiswal
authors.forename: Sanjay
authors.initials: S
authors.lastname: Navani
authors.forename: Per-Henrik
authors.initials: PH
authors.lastname: Edqvist
authors.forename: Fredrik
authors.initials: F
authors.lastname: Pontén
authors.forename: Elena
authors.initials: E
authors.lastname: Tchougounova
authors.forename: Anja
authors.initials: A
authors.lastname: Smits
authors.forename: Tamador
authors.initials: T
authors.lastname: Elsir
authors.forename: Joachim
authors.initials: J
authors.lastname: Gullbo
authors.forename: Johan
authors.initials: J
authors.lastname: Lennartsson
authors.forename: Michael
authors.initials: M
authors.lastname: Bergqvist
authors.forename: Simon
authors.initials: S
authors.lastname: Ekman
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000704:Analysis of Variance; D000951:Antigens, Neoplasm / Q000378:metabolism; D014408:Biomarkers, Tumor / Q000378:metabolism*; D001932:Brain Neoplasms / Q000378:metabolism* / Q000401:mortality* / Q000473:pathology / Q000628:therapy; D000071231:Carbonic Anhydrase IX; D002256:Carbonic Anhydrases / Q000378:metabolism; D005260:Female; D016222:Fibroblast Growth Factor 2 / Q000378:metabolism*; D005910:Glioma / Q000378:metabolism* / Q000401:mortality* / Q000473:pathology / Q000628:therapy; D006801:Humans; D018960:Hyaluronan Receptors / Q000378:metabolism; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000378:metabolism*; D011379:Prognosis; D016271:Proto-Oncogene Proteins c-myc / Q000378:metabolism; D012044:Regression Analysis; D012189:Retrospective Studies; D046888:Tissue Array Analysis
chemical_list: D000951:Antigens, Neoplasm; D014408:Biomarkers, Tumor; C497483:CD44 protein, human; D018960:Hyaluronan Receptors; C489427:MYC protein, human; D009363:Neoplasm Proteins; D016271:Proto-Oncogene Proteins c-myc; D016222:Fibroblast Growth Factor 2; C089226:CA9 protein, human; D000071231:Carbonic Anhydrase IX; D002256:Carbonic Anhydrases