Expression Profile of LGR5 and Its Prognostic Significance in Colorectal Cancer Progression

Bo Gun Jang, Hye Sung Kim, Weon Young Chang, Jeong Mo Bae, Woo Ho Kim, Gyeong Hoon Kang

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

We investigated the expression profile of leucine-rich, repeat-containing, G-protein–coupled receptor 5 (LGR5) during colorectal cancer (CRC) progression and determined the prognostic impact of LGR5 in a large cohort of CRC samples. LGR5 expression was higher in CRCs than in normal mucosa, and was not associated with other cancer stem cell markers. LGR5 positivity was observed in 68% of 788 CRCs and was positively correlated with older age, moderately to well-differentiated cells, and nuclear β-catenin expression. Enhanced LGR5 expression remained persistent during the adenoma–carcinoma transition, but markedly declined in the budding cancer cells at the invasive fronts, which was not due to altered wingless-type mouse mammary tumor virus integration site family (Wnt) or epithelial–mesenchymal transition signaling. LGR5 showed negative correlations with microsatellite instability and CpG island methylator phenotype, and was not associated with KRAS or BRAF mutation. Notably, LGR5 positivity was an independent prognostic marker for better clinical outcomes in CRC patients. LGR5 overexpression attenuated tumor growth by decreasing ERK phosphorylation along with decreased colony formation and migration abilities in DLD1 cells. Likewise, knockdown of LGR5 expression resulted in a decline in the colony-forming and migration capacities in LoVo cells. Taken together, our data suggest a suppressive role of LGR5 in CRC progression.

Original languageEnglish
Pages (from-to)2236-2250
Number of pages15
JournalAmerican Journal of Pathology
Volume188
Issue number10
DOIs
StatePublished - Oct 2018

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Leucine
Colorectal Neoplasms
Virus Integration
Mouse mammary tumor virus
Catenins
Microsatellite Instability
CpG Islands
Aptitude
Neoplastic Stem Cells
Neoplasms
Mucous Membrane
Biomarkers
Phosphorylation
Phenotype
Mutation
Growth

Cite this

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title = "Expression Profile of LGR5 and Its Prognostic Significance in Colorectal Cancer Progression",
abstract = "We investigated the expression profile of leucine-rich, repeat-containing, G-protein–coupled receptor 5 (LGR5) during colorectal cancer (CRC) progression and determined the prognostic impact of LGR5 in a large cohort of CRC samples. LGR5 expression was higher in CRCs than in normal mucosa, and was not associated with other cancer stem cell markers. LGR5 positivity was observed in 68{\%} of 788 CRCs and was positively correlated with older age, moderately to well-differentiated cells, and nuclear β-catenin expression. Enhanced LGR5 expression remained persistent during the adenoma–carcinoma transition, but markedly declined in the budding cancer cells at the invasive fronts, which was not due to altered wingless-type mouse mammary tumor virus integration site family (Wnt) or epithelial–mesenchymal transition signaling. LGR5 showed negative correlations with microsatellite instability and CpG island methylator phenotype, and was not associated with KRAS or BRAF mutation. Notably, LGR5 positivity was an independent prognostic marker for better clinical outcomes in CRC patients. LGR5 overexpression attenuated tumor growth by decreasing ERK phosphorylation along with decreased colony formation and migration abilities in DLD1 cells. Likewise, knockdown of LGR5 expression resulted in a decline in the colony-forming and migration capacities in LoVo cells. Taken together, our data suggest a suppressive role of LGR5 in CRC progression.",
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Expression Profile of LGR5 and Its Prognostic Significance in Colorectal Cancer Progression. / Jang, Bo Gun; Kim, Hye Sung; Chang, Weon Young; Bae, Jeong Mo; Kim, Woo Ho; Kang, Gyeong Hoon.

In: American Journal of Pathology, Vol. 188, No. 10, 10.2018, p. 2236-2250.

Research output: Contribution to journalArticle

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