Elevated expression of survivin-splice variants predicts a poor outcome for soft-tissue sarcomas patients.
The aim of this study was to investigate the level and the prognostic value of the expression of different survivin transcript variants--survivin, survivin-DeltaEx3 and survivin-2B--in tumours of 76 soft tissue sarcoma (STS) patients. The expression of survivin transcript variants in STS tissue samples and in 12 nonmalignant control tissues was analysed by quantitative RT-PCRs. Expression levels of all survivin transcript variants were strongly elevated in STS compared to normal tissues. A positive correlation between expression of splice variants and tumour stage was found (P=0.02; chi2 test). The multivariate Cox's proportional hazards regression model revealed a 7.3-fold increased risk of tumour-related death for patients with survivin-DeltaEx3 overexpressing tumours (P=0.007). The effect of surivivin (wildtype variant) and survivin-2B was less pronounced but still significant (2.2- and 1.9-fold, resp., P<0.05 each). Our results show for the first time that mRNA expression of survivin-variants is significantly correlated to a poor prognosis for STS patients, and we suggest expression of survivin splice variants together with tumour stage as independent predictor of survival.
Taubert
Helge
H
Institute of Pathology, Faculty of Medicine, University Halle-Wittenberg, Magdeburger Strasse 14, D-06097 Halle/Saale, Germany. helge.taubert@medizin.uni-halle.de
Kappler
Matthias
M
Bache
Matthias
M
Bartel
Frank
F
Köhler
Thomas
T
Lautenschläger
Christine
C
Blümke
Karen
K
Würl
Peter
P
Schmidt
Hannelore
H
Meye
Axel
A
Hauptmann
Steffen
S
D014408:Biomarkers, Tumor / Q000032:analysis / Q000096:biosynthesis*; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins; D008297:Male; D008869:Microtubule-Associated Proteins / Q000032:analysis / Q000096:biosynthesis*; D009363:Neoplasm Proteins / Q000032:analysis / Q000096:biosynthesis*; D009367:Neoplasm Staging / Q000379:methods; D011379:Prognosis; D020033:Protein Isoforms / Q000032:analysis / Q000096:biosynthesis; D022821:RNA Splice Sites; D012333:RNA, Messenger / Q000096:biosynthesis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012509:Sarcoma / Q000235:genetics* / Q000401:mortality*; D016019:Survival Analysis; D000077022:Survivin
C107489:BIRC5 protein, human; D014408:Biomarkers, Tumor; D051034:Inhibitor of Apoptosis Proteins; D008869:Microtubule-Associated Proteins; D009363:Neoplasm Proteins; D020033:Protein Isoforms; D022821:RNA Splice Sites; D012333:RNA, Messenger; D000077022:Survivin