Prognostic value of LGR5 in colorectal cancer: a meta-analysis

Abstract

Objective: Leucine-rich repeat-containing G protein-coupled receptor 5 (LGR5) has recently been reported to be a marker of cancer stem cells (CSCs) in colorectal cancer (CRC), and the prognostic value of LGR5 in CRC has been evaluated in several studies. However, the conclusions remain controversial. In this study, we aimed to evaluate the association between the expression of LGR5 and the outcome of CRC patients by performing a meta-analysis.

Methods: We systematically searched for relevant studies published up to February 2014 using the PubMed, Web of Science, EMBASE and Wangfang databases. Only articles in which LGR5 expression was detected by immunohistochemistry were included. A meta-analysis was performed using STATA 12.0, and pooled hazard ratios (HRs) with 95% confidence intervals (CIs) were used to estimate the strength of the association between LGR5 expression and the prognosis of CRC patients.

Results: A total of 7 studies comprising 1833 CRC patients met the inclusion criteria, including 6 studies comprising 1781 patients for overall survival (OS) and 3 studies comprising 528 patients for disease-free survival (DFS). Our results showed that high LGR5 expression was significantly associated with poor prognosis in terms of OS (HR: 1.87, 95% CI: 1.23-2.84; P = 0.003) and DFS (HR: 2.44, 95% CI: 1.49-3.98; P<0.001). Further subgroup analysis revealed that many factors, including the study region, number of patients, follow-up duration and cutoff value, affected the significance of the association between LGR5 expression and a worse prognosis in patients with CRC. In addition, there was no evidence of publication bias, as suggested by Begg's and Egger's tests.

Conclusions: The present meta-analysis indicated that high LGR5 expression was associated with poor prognosis in patients with CRC and that LGR5 is an efficient prognostic factor in CRC.

Figure 1. Flow diagram showing the study selection procedure.

Figure 2. Forest plot of the hazard ratio (HR) for the association of LGR5 expression with overall survival (OS) in colorectal cancer patients in 5 studies.

HR>1 implied poor survival, and high LGR5 expression was significantly associated with worse OS in CRC patients.

Figure 3. Forest plot of the hazard ratio (HR) for the association of LGR5 expression with disease-free survival (DFS) in colorectal cancer patients in 3 studies.

HR>1 implied poor survival, and high LGR5 expression was significantly associated with worse DFS in CRC patients.

Figure 4. Begg’s funnel plot for all studies included in this meta-analysis.

(A) Begg’s funnel plot assessing LGR5 expression and OS in colorectal cancer patients. (B) Begg’s funnel plot assessing LGR5 expression and DFS in colorectal cancer patients.

Figure 5. Egger’s test to detect publication bias.

(A) Egger’s test assessing LGR5 expression and OS in colorectal cancer patients. (B) Egger’s test assessing LGR5 expression and DFS in colorectal cancer patients.