Clinicopathologic and prognostic significance of LGR5, a cancer stem cell marker in patients with colorectal cancer.
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ABSTRACT:
SUBMITTER: Ihemelandu C
PROVIDER: S-EPMC7000925 | biostudies-literature | 2019 Nov
REPOSITORIES: biostudies-literature
Publications
Clinicopathologic and prognostic significance of LGR5, a cancer stem cell marker in patients with colorectal cancer.
Ihemelandu Chukwuemeka C Naeem Aisha A Parasido Erika E Berry Deborah D Chaldekas Krysta K Harris Brent T BT Rodriguez Olga O Albanese Christopher C
Colorectal cancer 20191112 4
<h4>Aim</h4>To analyze the clinicopathologic and prognostic significance of Leucine-rich repeat-containing G-protein-coupled receptor 5 (LGR5), a cancer stem cell marker expression in a cohort of colorectal cancer patients (CRC).<h4>Patients & methods</h4>A total of 76 formalin-fixed paraffin-embedded tissue blocks of primary or metastatic tumors from 49 CRC patients were collected for duration 2009-2015. LGR5 expression was assessed through immunohistochemical staining of a tissue microarray.<h ...[more]
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Project description: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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