A novel splice variant of the stem cell marker LGR5/GPR49 is correlated with the risk of tumor-related death in soft-tissue sarcoma patients

  • Background The human leucine-rich, repeat-containing G protein-coupled receptor (LGR) 5, also called GPR49, is a marker of stem cells in adult intestinal epithelium, stomach and hair follicles. LGR5/GPR49 is overexpressed in tumors of the colon, ovary and liver and in basal cell carcinomas. Moreover, an expression in skeletal muscle tissues was also detected. However, there has been no investigation regarding the expression and function of LGR5/GPR49 in soft-tissue sarcomas (STS) yet. Methods Seventy-seven frozen tumor samples from adult STS patients were studied using quantitative real-time TaqMan™ PCR analysis. The mRNA levels of wild type LGR5/GPR49 and a newly identified splice variant oBackground The human leucine-rich, repeat-containing G protein-coupled receptor (LGR) 5, also called GPR49, is a marker of stem cells in adult intestinal epithelium, stomach and hair follicles. LGR5/GPR49 is overexpressed in tumors of the colon, ovary and liver and in basal cell carcinomas. Moreover, an expression in skeletal muscle tissues was also detected. However, there has been no investigation regarding the expression and function of LGR5/GPR49 in soft-tissue sarcomas (STS) yet. Methods Seventy-seven frozen tumor samples from adult STS patients were studied using quantitative real-time TaqMan™ PCR analysis. The mRNA levels of wild type LGR5/GPR49 and a newly identified splice variant of LGR5/GPR49 lacking exon 5 (that we called GPR49Δ5) were quantified. Results A low mRNA expression level of GPR49Δ5, but not wild type LGR5/GPR49, was significantly correlated with a poor prognosis for the disease-associated survival of STS patients (RR = 2.6; P = 0.026; multivariate Cox's regression hazard analysis). Furthermore, a low mRNA expression level of GPR49Δ5 was associated with a shorter recurrence-free survival (P = 0.043). However, tumor onset in patients with a lower expression level of GPR49Δ5 mRNA occurred 7.5 years later (P = 0.04) than in patients with a higher tumor level of GPR49Δ5 mRNA. Conclusion An attenuated mRNA level of the newly identified transcript variant GPR49Δ5 is a negative prognostic marker for disease-associated and recurrence-free survival in STS patients. Additionally, a lower GPR49Δ5 mRNA level is associated with a later age of tumor onset. A putative role of GPR49Δ5 expression in tumorigenesis and tumor progression of soft tissue sarcomas is suggested.show moreshow less

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Metadaten
Author:Swetlana Rot, Helge Taubert, Matthias Bache, Greither Thomas, Peter Würl, Alexander W. Eckert, Johannes Schubert, Dirk Vordermark, Matthias Kappler
URN:urn:nbn:de:bvb:29-opus-31887
Title of the journal / compilation:BMC Cancer 11.429 (2011): 23.03.2012 <http://www.biomedcentral.com/1471-2407/11/429>
Document Type:Article
Language:English
Date of Publication (online):2012/03/23
Publishing Institution:Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU)
Release Date:2012/03/23
SWD-Keyword:-
Original publication:BMC Cancer 11.429 (2011): 23.03.2012 <http://www.biomedcentral.com/1471-2407/11/429>
Institutes:Medizinische Fakultät -ohne weitere Spezifikation-
Dewey Decimal Classification:610 Medizin und Gesundheit
Collections:Von der FAU geförderte Open Access Artikel 2011

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