title: Prognosis in human glioblastoma based on expression of ligand growth hormone-releasing hormone, pituitary-type growth hormone-releasing hormone receptor, its splicing variant receptors, EGF receptor and PTEN genes.
abstract: OBJECTIVE
  Glioblastoma (GB) is the most frequent brain tumor. Despite recent improvement in therapeutic strategies, the prognosis of GB remains poor. Growth hormone-releasing hormone (GHRH) may act as a growth factor; antagonists of GHRH have been successfully applied for experimental treatment of different types of tumors. The expression profile of GHRH receptor, its main splice variant SV1 and GHRH have not been investigated in human GB tissue samples.
  
  
  METHODS
  We examined the expression of GHRH, full-length pituitary-type GHRH receptor (pGHRHR), its functional splice variant SV1 and non-functional SV2 by RT-PCR in 23 human GB specimens. Epidermal growth factor receptor (EGFR) and phosphatase and tensin homolog gene (PTEN) expression levels were also evaluated by quantitative RT-PCR. Correlations between clinico-pathological parameters and gene expressions were analyzed.
  
  
  RESULTS
  Expression of GHRH was found to be positive in 61.9 % of samples. pGHRH receptor was not expressed in our sample set, while SV1 could be detected in 17.4 % and SV2 in 8.6 % of the GB tissues. In 65.2 and 78.3 % of samples, significant EGFR over-expression or PTEN under-representation could be detected, respectively. In 47.8 % of cases, EGFR up-regulation and PTEN down-regulation occurred together. Survival was significantly poorer in tumors lacking GHRH expression. This worse prognosis in GHRH negative group remained significant even if SV1 was also expressed.
  
  
  CONCLUSIONS
  Our study shows that GHRH and SV1 genes expressed in human GB samples and their expression patterns are associated with poorer prognosis.
authors.affiliation: Department of Neurosurgery, University of Debrecen, Nagyerdei krt. 98, Debrecen, 4032, Hungary.
authors.forename: Géza
authors.initials: G
authors.lastname: Mezey
authors.forename: Andrea
authors.initials: A
authors.lastname: Treszl
authors.forename: Andrew V
authors.initials: AV
authors.lastname: Schally
authors.forename: Normann L
authors.initials: NL
authors.lastname: Block
authors.forename: Laura
authors.initials: L
authors.lastname: Vízkeleti
authors.forename: Alíz
authors.initials: A
authors.lastname: Juhász
authors.forename: Almos
authors.initials: A
authors.lastname: Klekner
authors.forename: János
authors.initials: J
authors.lastname: Nagy
authors.forename: Margit
authors.initials: M
authors.lastname: Balázs
authors.forename: Gábor
authors.initials: G
authors.lastname: Halmos
authors.forename: László
authors.initials: L
authors.lastname: Bognár
mesh_terms: D000328:Adult; D000368:Aged; D001932:Brain Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000401:mortality* / Q000601:surgery; D066246:ErbB Receptors / Q000235:genetics / Q000378:metabolism*; D005260:Female; D005629:Frozen Sections; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D005909:Glioblastoma / Q000235:genetics / Q000378:metabolism* / Q000401:mortality* / Q000601:surgery; D013007:Growth Hormone-Releasing Hormone / Q000378:metabolism*; D006801:Humans; D006814:Hungary / Q000453:epidemiology; D053208:Kaplan-Meier Estimate; D008024:Ligands; D008297:Male; D008875:Middle Aged; D051059:PTEN Phosphohydrolase / Q000235:genetics / Q000378:metabolism*; D011379:Prognosis; D012326:RNA Splicing; D018013:Receptors, Neuropeptide / Q000235:genetics / Q000378:metabolism*; D018017:Receptors, Pituitary Hormone-Regulating Hormone / Q000235:genetics / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D008024:Ligands; D018013:Receptors, Neuropeptide; D018017:Receptors, Pituitary Hormone-Regulating Hormone; D013007:Growth Hormone-Releasing Hormone; C512478:EGFR protein, human; D066246:ErbB Receptors; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human; C048250:somatotropin releasing hormone receptor