title: Expression and prognostic significance of survivin splice variants in diffusely infiltrating astrocytoma.
abstract: BACKGROUND
  Alternative splicing of survivin (BIRC5) pre-mRNA generates the common isoform survivin and five additional splice variants: survivin2B, survivinΔEx3, survivin2α, survivin3B and survivin3α. Although the common isoform survivin has been shown to be involved in tumourigenesis and progression of various tumours, including diffusely infiltrating astrocytoma, the expression of other survivin splice variants in astrocytoma has not been fully investigated. Aims To evaluate the expression status and particularly prognostic significance of survivin splice variants in diffusely infiltrating astrocytoma.
  
  
  METHODS
  mRNA expression of the six survivin variants in 73 diffusely infiltrating astrocytoma and 18 normal brain tissue samples was investigated by using reverse transcription-PCR (RT-PCR), and the total survivin protein expression by western analysis and immunohistochemistry. Association of survivin and its splice variants with tumour grade and prognosis was examined by statistical and survival analysis.
  
  
  RESULTS
  The survivin, survivinΔEx3, survivin2B and survivin2α splice variants were significantly elevated in diffusely infiltrating astrocytoma, and were barely detectable or not detectable at all in normal brain tissue. Survivin3B and survivin3α were not detected in these samples. The positive rates of the expressed four variants increased with astrocytoma grade. Significantly, expression of these splice variants was associated with much poorer disease-specific and progression-free survival (Kaplan-Meier analysis, p≤0.002). Cox regression model further indicated survivin2α mRNA expression and nuclear survivin immunostaining to be significant independent negative prognostic factors.
  
  
  CONCLUSIONS
  The survivin, survivinΔEx3, survivin2B and survivin2α splice variants were significantly elevated in astrocytoma, and were associated with tumour grade and poorer prognosis.
authors: Laboratory of Pathology, State Key Laboratory of Biotherapy, West China Hospital, Chengdu, China.
authors: Ying
authors: Y
authors: Huang
authors: Xueqin
authors: X
authors: Chen
authors: Ni
authors: N
authors: Chen
authors: Ling
authors: L
authors: Nie
authors: Miao
authors: M
authors: Xu
authors: Qiao
authors: Q
authors: Zhou
mesh_terms: D000328:Adult; D017398:Alternative Splicing / Q000235:genetics*; D001254:Astrocytoma / Q000235:genetics / Q000378:metabolism*; D015153:Blotting, Western; D001932:Brain Neoplasms / Q000235:genetics / Q000378:metabolism*; D018450:Disease Progression; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D051034:Inhibitor of Apoptosis Proteins / Q000378:metabolism*; D053208:Kaplan-Meier Estimate; D008297:Male; D009363:Neoplasm Proteins / Q000378:metabolism*; D011379:Prognosis; D012322:RNA Precursors / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D000077022:Survivin
chemical_list: C107489:BIRC5 protein, human; D051034:Inhibitor of Apoptosis Proteins; D009363:Neoplasm Proteins; D012322:RNA Precursors; D000077022:Survivin