Lgr5 expression is a valuable prognostic factor for colorectal cancer: evidence from a meta-analysis

Background: Lgr5 has recently been identified as a reliable biomarker of cancer stem cells (CSCs) in colorectal cancer (CRC); however, its prognostic value is still controversial. Methods: We searched PubMed, Web of Science, and Wanfang databases with identical strategies to retrieve articles. We evaluated the impact of Lgr5 expression on survival of CRC patients through meta-analysis. Results: A total of 12 studies comprising 2600 patients revealed that Lgr5 overexpression was negatively associated with overall survival (OS) (HR = 1.73, 95 % CI: 1.28-2.33; P = 0.00) and disease free survival (DFS) (HR = 2.89, 95 % CI: 1.89-4.44; P = 0.000) in CRC patients. Subgroup analysis suggested that Lgr5 overexpression was significantly associated with worse OS in subgroups with IHC as the method of Lgr5 assessment (HR = 2.01, 95 % CI: 1.39-2.89; P = 0.001), patients from Asia (HR = 1.81, 95 % CI: 1.27-2.58; P = 0.000), and NOS scores greater than 6 (HR = 2.12, 95 % CI: 1.41-3.19; P = 0.000). Furthermore, sensitivity analysis showed that the estimated HR ranged from 1.6 to 1.86 upon excluding one study sequentially from each analysis. In addition, Lgr5 overexpression was significantly associated with deep invasion of CRC (OR = 0.39, 95 % CI: 0.17-0.87; P = 0.002), lymphnode metastasis (OR = 0.45, 95 % CI: 0.26-0.76; P = 0.003), distant metastasis (OR = 0.37, 95 % CI: 0.22-0.62; P = 0.000), and AJCC stage (OR = 0.35, 95 % CI: 0.15-0.78; P = 0.01). However, Lgr5 overexpression was not correlated with tumor grade (OR = 0.75 95 % CI: 0.37-1.54; P = 0.433). Conclusions: This study shows that Lgr5 can be a valuable and reliable prognostic factor of colorectal cancer progression.