Lgr5 is a potential marker of colorectal carcinoma stem cells that correlates with patient survival

Abstract

BackgroundLgr5 (leucine-rich-repeat-containing G-protein-coupled receptor 5) has recently been identified as an intestinal stem cell marker. In order to determine whether Lgr5 is a potential marker of cancer stem cells, we investigated whether Lgr5 expression correlated with Ki-67 expression and prognosis in colorectal carcinoma.MethodsLgr5 and Ki-67 expression were evaluated by immunohistochemistry in 192 colorectal carcinoma specimens. Selection of side population (SP) cells was performed by staining with Hoechest 33342, and Lgr5 expression in Colo205 SP cells was then detected by immunofluorescence.ResultsLgr5 expression was significantly higher in carcinoma than in normal mucosa (P=0.001). Lgr5 was positively correlated with histological grade (P=0.001), depth of invasion (P=0.001), lymph node metastasis (P=0.001), distant metastasis (P=0.004), pTNM stage (P=0.001), and Ki-67 (r=0.446, P=0.001). Multivariate analysis showed that the effect of Lgr5 on survival was independent of Ki-67 (P=0.037). In the in vitro study, Hoechst low-staining cells were counted in 7% of the Colo205 colon cancer cell line population, and Lgr5 expression was strikingly stronger in Hoechst low-staining cells than in high-staining cells (P=0.001).ConclusionsThese findings suggest that Lgr5 may play an important role in the progression and prognosis of colorectal carcinoma, and may be a potential new therapeutic target for the treatment of colorectal cancer patients. It may also be considered as a potential marker for colorectal cancer stem cells (CSCs).

TROY is a promising prognostic biomarker in patients with colorectal cancer

“…Regarding CRC, many study groups reported that LGR5 is overexpressed in CRC tissues and is associated with unfavorable outcome in CRC patients (24)(25)(26)(27). In the present study, although univariate analysis showed overexpression of LGR5 to be a possible biomarker of unfavorable outcome of CRC, its clinical usefulness in predicting relapse of CRC was not as expected.…”

Overexpression of Lgr5 correlates with resistance to 5-FU-based chemotherapy in colorectal cancer

“…Similarly, Kleist et al [30] investigated the expression pattern of Lgr5 and found that 92 % of primary CRC tumors and 52 % of distant metastases showed positive Lgr5 immunoreactivity. In addition, Wu et al [31] also found that Lgr5 expression was positively correlated with distant and lymph node metastases. These authors reported a significant relationship between Lgr5 expression in tumors and the corresponding distant metastases, which is in agreement with the present study.…”

Increased expression of Lgr5 is associated with chemotherapy resistance in human gastric cancer

“…Lgr5 is a potential marker of adult stem cells of the small intestine, colon, stomach and hair follicle bulge (9)(10)(11). Increased expression of Lgr5 has been investigated in several types of human cancer, including hepatocellular carcinoma (7), gastric (12), colorectal (13)(14)(15) and ovarian cancer (16), basal cell carcinoma (17), esophageal adenocarcinoma (18) and brain cancer (19). In colorectal cancer, increased Lgr5 expression was identified in the spheroid cells (20), making it an ideal marker of colorectal cancer stem cells (CSCs) (13,14).…”