Prognostic Value of Long Noncoding RNA CRNDE as a Novel Biomarker in Solid Cancers: An Updated Systematic Review and Meta-Analysis

Background: Long noncoding RNA colorectal neoplasia differentially expressed (CRNDE) has been reported to exhibit a potential oncogenic role in the development of human cancers. However, the clinical value of CRNDE expression in various cancers still remains unclear. Herein, we conducted a meta-analysis to investigate the association between CRNDE and clinical outcomes in solid cancers. Methods: A systematic search was performed though the PubMed, EMBASE, Web of Science, Ovid, Cochrane library, CNKI and WanFang databases for eligible studies on clinical values of CRNDE in solid cancers. The pooled hazard ratios (HRs) or odd ratios (ORs) with 95% confidence intervals (CIs) were used to evaluate the link between CRNDE and clinical outcomes. Results: A total of 3690 patients from 20 studies (including 2 studies have 2 cohorts, respectively) were included. The results suggested that elevated CRNDE expression predicted a poor overall survival (OS) for in 13 types of solid cancers (HR=1.46, 95% CI: 1.33-1.58, P<0.001) with no heterogeneity (I-2=21.8%, P=0.19). Subgroup analysis indicated a significant association between high CRNDE expression and shorter OS in the studies with digestive system cancers (HR=1.42, 95% CI: 1.28-1.55, P<0.001), qRT-PCR method (HR=1.45, 95% CI: 1.30-1.59, P<0.001), sample size >100 (HR=1.44, 95% CI: 1.32-1.57, P<0.001), and NOS>7 (HR=1.50, 95% CI: 1.23-1.78, P<0.001). Furthermore, the pooled results showed that CRNDE was an independent prognostic factor for OS in cancer patients (HR=1.37, 95% CI: 1.22-1.52, P<0.001). In addition, we also revealed that CRNDE was positively related to tumor size (OR=2.10, 95% CI: 1.68-2.63, P<0.001), TNM stage (OR=2.86, 95% CI: 2.29-3.56, P<0.001), lymph node metastasis (LNM) (OR=3.21, 95% CI: 2.01-5.13, P<0.001), and distant metastasis (OR=4.36, 95% CI: 2.36-8.07, P<0.001). Although the probable evidences of publication bias were found in the studies with OS, tumor size, TNM stage or LNM, the trim and fill analysis confirmed the reliability of these results was not affected. Conclusion: Elevated CRNDE expression was associated with larger tumor size, advanced TNM stage, worse LNM and distant metastasis, and shorter OS, suggesting that CRNDE may act as an independent prognostic biomarker in solid cancers.