Expression of TRAIL-splice variants in gastric carcinomas: identification of TRAIL-γ as a prognostic marker.
BACKGROUND
TNF-related apoptosis inducing ligand (TRAIL) belongs to the TNF-superfamily that induces apoptotic cell death in a wide range of neoplastic cells in vivo as well as in vitro. We identified two alternative TRAIL-splice variants, i.e. TRAIL-β and TRAIL-γ that are characterized by the loss of their proapoptotic properties. Herein, we investigated the expression and the prognostic values of the TRAIL-splice variants in gastric carcinomas.


METHODS
Real time PCR for amplification of the TRAIL-splice variants was performed in tumour tissue specimens and corresponding normal tissues of 41 consecutive patients with gastric carcinoma. Differences on mRNA-expression levels of the TRAIL-isoforms were compared to histo-pathological variables and correlated with survival data.


RESULTS
All three TRAIL-splice variants could be detected in both non-malignant and malignant tissues, irrespective of their histological staging, grading or tumour types. However, TRAIL-β exhibited a higher expression in normal gastric tissue. The proapoptotic TRAIL-α expression was increased in gastric carcinomas when compared to TRAIL-β and TRAIL-γ. In addition, overexpression of TRAIL-γ was associated with a significant higher survival rate.


CONCLUSIONS
This is the first study that investigated the expression of TRAIL-splice variants in gastric carcinoma tissue samples. Thus, we provide first data that indicate a prognostic value for TRAIL-γ overexpression in this tumour entity.
Department of Surgery A, Heinrich Heine University and University Hospital Duesseldorf, Moorenstrasse 5, 40225 Duesseldorf, Germany. andreas.krieg@med.uni-duesseldorf.de
Andreas
A
Krieg
Sabrina
S
Mersch
Nadine
N
Wolf
Nikolas H
NH
Stoecklein
Pablo E
PE
Verde
Jan Schulte
JS
am Esch
Sebastian
S
Heikaus
Helmut E
HE
Gabbert
Wolfram T
WT
Knoefel
Csaba
C
Mahotka
D000230:Adenocarcinoma / Q000235:genetics / Q000378:metabolism* / Q000401:mortality; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000032:analysis*; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D016016:Proportional Hazards Models; D020033:Protein Isoforms; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013274:Stomach Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000401:mortality; D053221:TNF-Related Apoptosis-Inducing Ligand / Q000032:analysis / Q000096:biosynthesis* / Q000235:genetics
D014408:Biomarkers, Tumor; D020033:Protein Isoforms; D053221:TNF-Related Apoptosis-Inducing Ligand; C505653:TNFSF10 protein, human