Dataset Information

LGR5 is associated with tumor aggressiveness in papillary thyroid cancer.

ABSTRACT:

Purpose

Leucine-rich repeat-containing G-protein-coupled receptor 5 (LGR5) is a cancer stem cell marker and a down-stream target in Wnt/?-catenin signaling. In human papillary thyroid cancer (PTC), over activation of Wnt/?-catenin has been associated with tumor aggressiveness.

Patients and methods

Using established human cell lines (TPC-1, KTC-1, Nthy-ori-3-1), we report LGR5 and R-spondin (RSPO1-3) overexpression in PTC and manipulate LGR5 and Wnt/?-catenin signaling via both pharmacologic and genetic interventions. We test the association of LGR5 tumor expression with markers of PTC aggressiveness using a Discovery Cohort (n = 26 patients) and a Validation Cohort (n = 157 patients). Lastly, we explore the association between LGR5 and the BRAFV600E mutation (n = 33 patients).

Results

Our results reveal that LGR5 and its ligand, RSPO, are overexpressed in human PTC, whereby Wnt/?-catenin signaling regulates LGR5 expression and promotes cellular migration. In two separate cohorts of patients, LGR5 and RSPO2 were associated with markers of tumor aggressiveness including: lymph node metastases, vascular invasion, increased tumor size, aggressive histology, advanced AJCC TNM stage, microscopic extra thyroidal extension, capsular invasion, and macroscopic invasion. As a biomarker, LGR5 positivity predicts lymph node metastasis with 95.5% sensitivity (95% CI 88.8%-98.7%) and 61% specificity (95% CI: 48.4%-72.4%) and has a negative predictive value (NPV) of 91.3% (95% CI 79.2%-97.5%) for lymph node metastatic disease. In human PTC, LGR5 is also strongly associated with the BRAFV600E mutation (p = 0.005).

Conclusion

We conclude that overexpression of LGR5 is associated with markers of tumor aggressiveness in human PTC. LGR5 may serve as a future potential biomarker for patient risk stratification and loco regional metastases in PTC.

SUBMITTER: Michelotti G

PROVIDER: S-EPMC4741472 | biostudies-literature | 2015 Oct

REPOSITORIES: biostudies-literature

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Publications

LGR5 is associated with tumor aggressiveness in papillary thyroid cancer.

Michelotti Gregory G Jiang Xiaoyin X Sosa Julie Ann JA Diehl Anna Mae AM Henderson Brittany Bohinc BB

Oncotarget 20151001 33

<h4>Purpose</h4>Leucine-rich repeat-containing G-protein-coupled receptor 5 (LGR5) is a cancer stem cell marker and a down-stream target in Wnt/β-catenin signaling. In human papillary thyroid cancer (PTC), over activation of Wnt/β-catenin has been associated with tumor aggressiveness.<h4>Patients and methods</h4>Using established human cell lines (TPC-1, KTC-1, Nthy-ori-3-1), we report LGR5 and R-spondin (RSPO1-3) overexpression in PTC and manipulate LGR5 and Wnt/β-catenin signaling via both pha ...[more]

PMID: 26416247

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Dataset Information

LGR5 is associated with tumor aggressiveness in papillary thyroid cancer.

Purpose

Patients and methods

Results

Conclusion

Publications

LGR5 is associated with tumor aggressiveness in papillary thyroid cancer.

Similar Datasets

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