Expression of TRAIL-splice variants in gastric carcinomas: identification of TRAIL-gamma as a prognostic marker
Andreas Krieg, Sabrina Mersch, Nadine Wolf, Nikolas H Stoecklein, Pablo E Verde, Jan Schulte am Esch, Sebastian Heikaus, Helmut E Gabbert, Wolfram T Knoefel and Csaba Mahotka
Abstract
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-? and TRAIL-? 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-? exhibited a higher expression in normal gastric tissue. The proapoptotic TRAIL-? expression was increased in gastric carcinomas when compared to TRAIL-? and TRAIL-?. In addition, overexpression of TRAIL-? 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-? overexpression in this tumour entity.

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