J Cancer Prev.  2016 Dec;21(4):279-287. 10.15430/JCP.2016.21.4.279.

Expression of Leucine-rich Repeat-containing G-protein Coupled Receptor 5 and CD44: Potential Implications for Gastric Cancer Stem Cell Marker

Affiliations
  • 1Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Korea. nayoungkim49@empas.com
  • 2Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, Korea.
  • 3Department of Pathology, Seoul National University Bundang Hospital, Seongnam, Korea.
  • 4Department of Internal Medicine, Chungbuk National University College of Medicine and Medical Research Institute, Cheongju, Korea.

Abstract

BACKGROUND
The human leucine-rich repeat-containing G-protein coupled receptor (LGR) 5 and CD44 are one of the candidates for the marker of gastric cancer stem cells. We compared the expressions of two genes among control, dysplasia and cancer groups.
METHODS
We compared the mRNA expression of LGR5, CD44 and CD44v8-10 and immunohistochemistry (IHC) of LGR5 and CD44 in gastric antral mucosa of 45 controls, 36 patients with gastric dysplasia, and 39 patients with early gastric cancer. Additionally, IHC of LGR5 in gastric body mucosa was analyzed. Normal mucosa adjacent to dysplastic or cancer lesions was used for the quantitative real-time-PCR and IHC.
RESULTS
Immunoreactivity of LGR5 in base of antral mucosa was higher in non-cancerous tissues of cancer than those of control (P = 0.006), whereas the expression of LGR5 mRNA was not different among the three groups. Immunostaining of LGR5 was much stronger in the antrum than in the body of stomach (P < 0.001). Although there was no difference in antral immunointensity of LGR5 according to the severity of intestinal metaplasia, stronger immunostaining was found in the body with an aggravation of intestinal metaplasia (P trend < 0.001). The expression of CD44v8-10 mRNA was higher in cancer patients than control subjects and patients with dysplasia (P = 0.018 and 0.009) while the expression of CD44 mRNA was higher in the control groups than the others.
CONCLUSIONS
IHC of LGR5 in crypt base and CD44 may be used for gastric CSC markers. LGR5 expression may be associated with the developing of corporal intestinal metaplasia. The expression of CD44v8-10 mRNA would be more suitable for gastric cancer stem cell marker than CD44 or LGR5 mRNA.

Keyword

LGR5 protein; Gastric cancer; Stem cell

MeSH Terms

GTP-Binding Proteins*
Humans
Immunohistochemistry
Metaplasia
Mucous Membrane
RNA, Messenger
Stem Cells*
Stomach
Stomach Neoplasms*
GTP-Binding Proteins
RNA, Messenger
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