Please use this identifier to cite or link to this item: http://dx.doi.org/10.25673/37975
Title: Prognostic impact of mRNA levels of LGR5 transcript variants in OSCC patients
Author(s): Rot, Swetlana
Kaune, Tom
Taubert, HelgeLook up in the Integrated Authority File of the German National Library
Greither, ThomasLook up in the Integrated Authority File of the German National Library
Kotrba, Johanna
Güttler, Antje
Wichmann, Henri
Bilkenroth, Udo
Wienke, AndreasLook up in the Integrated Authority File of the German National Library
Al-Nawas, BilalLook up in the Integrated Authority File of the German National Library
Bache, MatthiasLook up in the Integrated Authority File of the German National Library
Vordermark, DirkLook up in the Integrated Authority File of the German National Library
Wickenhauser, Claudia
Bethmann, Daniel
Eckert, Alexander W.Look up in the Integrated Authority File of the German National Library
Kappler, MatthiasLook up in the Integrated Authority File of the German National Library
Issue Date: 2019
Type: Article
Language: English
Abstract: Background The human leucine-rich, repeat-containing G protein-coupled receptor 5 (LGR5) is a stem cell marker in numerous adult tissues and is overexpressed in a large number of human carcinoma including colon cancer, breast cancer and oral squamous cell carcinomas (OSCC). The role of the full length transcript (LGR5FL) in progression and prognosis of several cancers was reported. However, the biological function of three splice variants of LGR5 (LGR5Δ5, LGR5Δ8 and LGR5Δ5–8) has yet to be thoroughly investigated. Methods Seventy-eight frozen tumor samples from adult OSCC patients were studied using quantitative real-time TaqMan™ PCR analysis. The mRNA levels of full length LGR5, the splice variant of LGR5 lacking exon 5 (LGR5Δ5), the splice variant of LGR5 lacking exon 8 (LGR5Δ8) and the mRNA level of all known transcript variants together (LGR5all) were quantified and correlated to overall and disease-specific survival of OSCC patients, clinical parameters and the mRNA level of different tumor-associated markers. Results An elevated level of tumoral LGR5Δ5 mRNA, but not LGR5FL, LGR5Δ8 or LGR5all mRNA was significantly associated with a poor prognosis for the overall and disease-specific survival of OSCC patients (hazard ratio (HR) = 2.0; p = 0.02; 95% CI: 1.1–3.7; HR = 3.2; p = 0.01; 95% CI: 1.3–8.0; multivariable Cox regression), respectively. Additionally, a higher tumoral level of LGR5Δ5 mRNA in primary tumors was associated with the occurrence of regional lymph node metastases in OSCC patients (odds ratio (OR) = 3.1; p = 0.022; 95% CI: 1.2–7.9; binary logistic regression). Furthermore, the mRNA levels of all investigated LGR5 transcript variants were significantly correlated with the mRNA expression of Wnt-target genes and markers of epithelial-to-mesenchymal transition (EMT). Conclusion The mRNA level of the LGR5 splice variant LGR5Δ5 is an independent negative prognostic marker for overall and disease-specific survival and metastasis in OSCC patients. Additionally, we suggest, all LGR5 transcript variants are involved in the EMT process mainly through activating the Wnt-signalling pathway.
URI: https://opendata.uni-halle.de//handle/1981185920/38218
http://dx.doi.org/10.25673/37975
Open Access: Open access publication
License: (CC BY 4.0) Creative Commons Attribution 4.0(CC BY 4.0) Creative Commons Attribution 4.0
Sponsor/Funder: Publikationsfond MLU
Journal Title: BMC cancer
Publisher: BioMed Central
Publisher Place: London
Volume: 19
Original Publication: 10.1186/s12885-019-5327-8
Appears in Collections:Open Access Publikationen der MLU

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