Diagnostic and prognostic value of circulating miR-21 for cancer: a systematic review and meta-analysis

Gene. 2014 Jan 1;533(1):389-97. doi: 10.1016/j.gene.2013.09.038. Epub 2013 Sep 26.


Background: MicroRNAs (miRNAs) have been reported to be aberrantly expressed in patients with cancer. Many studies have shown that circulating miRNAs could play potential roles as diagnostic and prognostic biomarkers of cancers. The aim of this meta-analysis is to summarize the role of circulating miR-21 as a biomarker in patients with a variety of carcinomas.

Material and methods: Eligible studies were identified and assessed for quality through multiple search strategies. For diagnostic meta-analysis, the sensitivity, specificity, and other measures of miR-21 in the diagnosis of cancer were pooled using bivariate random-effects approach models. For prognostic meta-analysis, pooled hazard ratios (HRs) of circulating miR-21 for survival were calculated.

Results: A total of 36 studies dealing with various carcinomas were included for the systemic review. Among them, 23 studies were finally enrolled in the global meta-analysis (17 studies for diagnosis and 6 studies for prognosis). For diagnostic meta-analysis, the overall pooled results for sensitivity, specificity, positive likelihood ratio (LRP), negative likelihood ratios (LRN) and diagnostic odds ratio (DOR) were 75.7% (95% CI: 67.1%-82.6%), 79.3% (95% CI: 74.2%-83.5%), 3.65 (95% CI: 2.83-4.70), 0.31 (95% CI: 0.22-0.43), and 11.88 (95% CI: 6.99-20.19), respectively. For prognostic meta-analysis, the pooled HR of higher miR-21 expression in circulation was 2.37 (95% CI: 1.83-3.06, P<0.001), which could significantly predict poorer survival in general carcinomas. Importantly, subgroup analysis suggested that higher expression of miR-21 correlated with worse overall survival (OS) significantly in carcinomas of digestion system (HR, 5.77 [95% CI: 2.65-12.52]).

Conclusions: Our findings suggest that circulating miR-21 may not suitable to be a diagnostic biomarker, but it has a prognostic value in patients with cancer.

Keywords: Biomarker; Cancer; Circulating miR-21; DOR; Diagnosis; GBM; HCC; HRs; HSROC; LRN; LRP; MicroRNAs; OS; PDCD4; PTEN; Prognosis; QUADAS; Quality Assessment of Diagnostic Accuracy Studies; RECK; TPM1; diagnostic odd ratio; false-negative; false-positive; fn; fp; glioma; hazard ratios; hepatocellular carcinoma; hierarchical summary receiver operating characteristics; miRNAs; negative likelihood ratio; overall survival; positive likelihood ratio; programmed cell death 4; qRT-PCR; quantitative real-time PCR; reversion-inducing cysteine-rich protein with Kazal motifs; tensin homolog; tn; tp; tropomyosin 1; true-negative; true-positive.

Publication types

  • Meta-Analysis
  • Research Support, Non-U.S. Gov't
  • Review
  • Systematic Review

MeSH terms

  • Biomarkers, Tumor / blood*
  • Humans
  • MicroRNAs / blood*
  • Neoplasms / blood
  • Neoplasms / diagnosis*
  • Neoplasms / pathology
  • Prognosis


  • Biomarkers, Tumor
  • MIRN21 microRNA, human
  • MicroRNAs