Prognostic impact of mRNA levels of LGR5 transcript variants in OSCC patients

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.

Transcriptomic Profiling of Fibropapillomatosis in Green Sea Turtles (Chelonia mydas) From South Texas

“…The increased tumor expression of NLRC5 is associated with better outcomes in human cancer ( 68 ) and is a target of interest in anti-tumor immunity in transmissible tumors of another endangered species; the Tasmanian devil ( 69 ). Furthermore, downregulation of LGR5 in FP (log 2 FoldChange = −4.56, p adj = 1.03 × 10 −9 ) may also demonstrate evidence of an anti-tumor response through regulation of the Wnt/β-catenin signaling pathway, as increased expression of LGR5 is associated with poor prognosis in glioma ( 70 ), breast cancer ( 71 ) and oral squamous cell carcinoma ( 72 ). The consistent identification of the alteration of genes involved in Wnt signaling in FP indicates that further in-depth exploration of this pathway in FP is warranted.…”

Transcriptomic profiling of fibropapillomatosis in green sea turtles (Chelonia mydas) from South Texas

“…Furthermore, downregulation of LGR5 in FP (log2FoldChange = −4.56, padj = 1.03×10 −9 ) may also demonstrate evidence of an anti-tumor response through regulation of the Wnt/β-catenin signaling pathway, as increased expression of LGR5 is associated with poor prognosis in glioma 66 , breast cancer 67 and oral squamous cell carcinoma. 68 The consistent identification of the alteration of genes involved in Wnt signaling in FP indicates that further in-depth exploration of this pathway in FP is warranted.…”

GP88/PGRN Serum Levels Are Associated with Prognosis for Oral Squamous Cell Carcinoma Patients

“…Twenty-six patients (27.1%) received radiotherapy subsequent to excision, 11 patients (11.5%) received chemotherapy with cisplatin, and one patient received taxol (1.0%). The patient group is part of the previously described cohort [ 41 , 42 ]. Demographic and clinicopathological data of the patients are summarized in Table 1 .…”