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Open Access Research article

Expression of TRAIL-splice variants in gastric carcinomas: identification of TRAIL-γ as a prognostic marker

Andreas Krieg1*, Sabrina Mersch1, Nadine Wolf2, Nikolas H Stoecklein1, Pablo E Verde3, Jan Schulte am Esch1, Sebastian Heikaus2, Helmut E Gabbert2, Wolfram T Knoefel1 and Csaba Mahotka2*

Author Affiliations

1 Department of Surgery A, Heinrich Heine University and University Hospital Duesseldorf, Moorenstrasse 5, 40225 Duesseldorf, Germany

2 Institute of Pathology, Heinrich Heine University and University Hospital Duesseldorf, Moorenstrasse 5, 40225 Duesseldorf, Germany

3 Coordination Centre for Clinical Trials, Heinrich Heine University and University Hospital Duesseldorf, Moorenstrasse 5, 40225 Duesseldorf, Germany

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BMC Cancer 2013, 13:384  doi:10.1186/1471-2407-13-384

Published: 12 August 2013

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-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.

Keywords:
TRAIL; Alternative splicing; Apoptosis; Gastric carcinoma