ArticlePloS one2015
Lgr5 Methylation in Cancer Stem Cell Differentiation and Prognosis-Prediction in Colorectal Cancer.
Article in PloS one, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers, 1 of them a synthesis that pooled it.
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Who cites it
16 citing papers in PubMed, 1 synthesis or guideline pooled it, 22 citations in OpenAlex.
- Prognostic DNA methylation markers for sporadic colorectal cancer: a systematic review.Clinical epigenetics · 2018Pooled it
- Low LAMA2 expression may affect drug resistance and prognosis in ovarian cancer via positive LGR5 coexpression.Translational cancer research · 2026Article
- Association between colorectal cancer stem cells' expression of LGR5 and the location of colorectal cancer.Gastroenterology and hepatology from bed to bench · 2025Article
- Epigenetic crosstalk between stem cells and tumors: mechanisms and emerging perspectives.American journal of stem cells · 2025Review
- Goblet cell differentiation subgroups in colorectal cancer.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- LGR5 expression and clinicopathological features of the invasive front in the fat infiltration area of pancreatic cancer.Diagnostic pathology · 2022Article
- Epigenetic Regulation of the Wnt/β-Catenin Signaling Pathway in Cancer.Frontiers in genetics · 2021Review
- Clinical implications of cancer stem cells in digestive cancers: acquisition of stemness and prognostic impact.Surgery today · 2020Review
- A novel microRNA boosts hyper-β-oxidation of fatty acids in liver by impeding CEP350-mediated sequestration of PPARα and thus restricts chronic hepatitis C.RNA biology · 2020Article
- Simulating the human colorectal cancer microenvironment in 3D tumor-stroma co-cultures in vitro and in vivo.Scientific reports · 2020Article
- Analysis of the high-dose-range radioresistance of prostate cancer cells, including cancer stem cells, based on a stochastic model.Journal of radiation research · 2019Article
- Involvement of methylation-associated silencing of formin 2 in colorectal carcinogenesis.World journal of gastroenterology · 2018Article
- Targeting LGR5 in Colorectal Cancer: therapeutic gold or too plastic?British journal of cancer · 2018Review
- Temporal and Spatial Expression of LGR5 After Acute Spinal Cord Injury in Adult Rats.Neurochemical research · 2016Article
- Lgr5+ stem cells and their progeny in mouse epidermis under regimens of exogenous skin carcinogenesis, and their absence in ensuing skin tumors.Oncotarget · 2016Article
- Wnt Signaling in Cancer Stem Cell Biology.Cancers · 2016Review
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Authors and funding
16 authors at 5 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
objectiveLeucine-rich-repeat-containing G-protein-coupled receptor 5 (lgr5) is a candidate marker for colorectal cancer stem cells (CSC). In the current study, we investigated the methylation status within thelgr5 promoter and evaluated its relationship with CSC differentiation, prognosis for colorectal cancer, and its clinicopathological features.
methodsThe methylation status within Lgr5 promoter was detected with a methylation-specific PCR in six colorectal cancer cell lines as well as 169 primary colorectal tumor tissues. Differentiation of CSC was examined with immunofluorescence and immunocytochemistry. Down-regulation of lgr5 was achieved with gene-specific siRNA. The associations between lgr5 methylation and the clinicopathological features as well as survival of patients were analyzed with statistical methods.
resultsThe lgr5 promoter was methylated to different degrees for the six colorectal cell lines examined, with complete methylation observed in HCT116 cells in which the lgr5 expression was partially recovered following DAC treatment. The stem-cell sphere formation from HCT116 cells was accompanied by increasing methylation within the lgr5 promoter and decreasing expression of lgr5. Knocking down lgr5 by siRNA also led to stem-cell spheres formation. Among primary colorectal tumors, 40% (67/169) were positive for lgr5 methylation, while none of the normal colon tissues were positive for lgr5 methylation. Furthermore, lgr5 methylation significantly associated with higher tumor grade, and negative distant metastasis (p < 0.05), as well as better prognosis (p = 0.001) in patients with colorectal cancer.
conclusionsOur data suggests that lgr5 methylation, through the regulation of lgr5 expression and colorectal CSC differentiation, may constitute a novel prognostic marker for colorectal cancer patients.
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