title: Lgr5 expression is a valuable prognostic factor for colorectal cancer: evidence from a meta-analysis.
abstract: 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.
authors.affiliation: Department of UItrasonic diagnosis, Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China. yangyanjiang11@163.com.
authors.forename: Yangyan
authors.initials: Y
authors.lastname: Jiang
authors.affiliation: Department of Pharmacology, Zhejiang University School of pharmacy, Hangzhou, China. wenlu256@gmail.com.
authors.forename: Wenlu
authors.initials: W
authors.lastname: Li
authors.affiliation: Department of Hematology, Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China. 21118135@zju.edu.cn.
authors.forename: Xin
authors.initials: X
authors.lastname: He
authors.affiliation: Department of Neurology, Third people's hospital, Huzhou, China. HongboZhang11@163.com.
authors.forename: Hongbo
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Department of Plastic surgery, Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China. fzj198727@163.com.
authors.forename: Fangzhen
authors.initials: F
authors.lastname: Jiang
authors.affiliation: Department of Oncology, Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China. pridechen@126.com.
authors.forename: Zhigang
authors.initials: Z
authors.lastname: Chen
mesh_terms: D000368:Aged; D014408:Biomarkers, Tumor / Q000032:analysis*; D015179:Colorectal Neoplasms / Q000401:mortality* / Q000473:pathology*; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D043562:Receptors, G-Protein-Coupled / Q000096:biosynthesis*
chemical_list: D014408:Biomarkers, Tumor; C116884:LGR5 protein, human; D043562:Receptors, G-Protein-Coupled