Short communicationDiagnostic and prognostic value of circulating miR-21 for cancer: A systematic review and meta-analysis
Introduction
Cancer is the leading cause of death in economically developed countries and the second leading cause of death in developing countries. About 12.7 million new cancer cases and 7.6 million new deaths are estimated to have occurred in 2008 worldwide (Jemal et al., 2011). Most of the cancers are difficult to diagnose because of non-specific clinical presentations, especially in early-stage. Though current diagnostic methods, such as imaging examination and biopsy, have significantly improved accuracy, these methods still have certain limitations as invasive and harmful procedure (Duffy, 2007). Also, we still do not have an effective predictor for prognosis, which could provide important information for clinical treatment. The circulating biomarkers used in current clinical practice are lack of sufficient accuracy. Therefore, it is still a great need to detect simple and reliable biomarker for diagnosing cancers and/or predicting the outcome of cancer patients.
MicroRNAs (miRNAs) are endogenous, small non-coding 18–25 nucleotide RNAs. These miRNAs could be post transcriptional gene regulators that paired to complementary sequences in the 3′ untranslated region (3′ UTR) of target mRNAs, leading to mRNA degradation or translational repression (Bartel, 2004, Bartel and Chen, 2004). These miRNAs could not only regulate gene-expression but also involve in various biogenesis which are associated with carcinogenesis, such as cell proliferation, cell cycle, apoptosis, angiogenesis, invasion, and metastasis (Chen et al., 2012a, Ivanovska et al., 2008, Lu et al., 2007, Takamizawa et al., 2004, Wang et al., 2011a, Wang et al., 2011b).
Evidences from clinical studies suggested that many miRNAs were deregulated in a variety of cancers, and the expression level of some miRNAs correlated with the stage of diseases. Hence, these miRNAs could play potential roles as diagnostic and prognostic biomarkers of cancers (Ferracin et al., 2010, Nana-Sinkam and Croce, 2010). miRNAs especially in circulation, such as serum and plasma, can be non-invasive biomarkers for cancer. Among them, miR-21 was the representative one since it has been extensively studied in various cancers. Many studies showed that the expression level of circulating miR-21 could distinguish cancer patients from healthy people and predict disease outcomes. However, there are inconsistent results for the diagnostic accuracy and the overall risk for prognosis associated with miR-21. Considering the limits of the single study, we conduct this systematic review and meta-analysis to evaluate the diagnostic efficacy and the prognostic significances of cell-free circulating miR-21 in patients with cancer. We also discussed the possibility of cell-free circulating miR-21 as diagnostic and/or prognostic biomarker in clinical practice.
Section snippets
Search strategy
We carefully searched online in PubMed and EMBASE until April 6, 2013 to identify relevant studies. Two distinct sets of key words were used simultaneously, namely ‘circulating/serum/plasma miR-21 and cancer’ and ‘miR-21 and cancer diagnosis or prognosis’. The cited references of retrieved articles were also scanned to identify any additional relevant studies.
Studies were considered eligible if they met the following criteria: (i) they studied the patients with any type of carcinoma; (ii) they
Literature search
528 records for circulating miR-21 and cancer were identified from a primary literature search in PubMed and EMBASE. After manually screening the titles, abstracts and keywords, 474 articles were excluded because they were review articles, letters, non-English articles, laboratory studies, or studies irrelevant to the current analysis. Then we analyzed the remaining 54 articles by reviewing each full text. Twenty-seven articles were omitted because of no cell-free blood sample. The candidate 36
Discussion
Development of suitable biomarkers is critical for diagnosing cancer or predicting patients' outcome. Nowadays, circulating miRNAs attracted much more attention for its high stability and great potential as biomarker. Among the various miRNAs, miR-21 was widely studied and was found aberrantly expressed in various cancers. However, the diagnostic accuracy and prognostic ability was inconsistent or even contradictory in literature.
The present meta-analysis has shown that, as a diagnostic
Conflicts of interest statements
There is no conflict of interest.
Acknowledgments
This manuscript is supported by the National Basic Research Program of China (973program) No. 2012CB9333004 and Clinical Trial Special Fund (11L01).
References (61)
MicroRNAs: genomics, biogenesis, mechanism, and function
Cell
(2004)Role of tumor markers in patients with solid cancers: a critical review
Eur. J. Intern. Med.
(2007)- et al.
The diagnostic odds ratio: a single indicator of test performance
J. Clin. Epidemiol.
(2003) Combination of plasma microRNAs with serum CA19-9 for early detection of pancreatic cancer
Int. J. Cancer
(2012)- et al.
Transgenic over-expression of the microRNA miR-17-92 cluster promotes proliferation and inhibits differentiation of lung epithelial progenitor cells
Dev. Biol.
(2007) - et al.
MicroRNA-21 regulates expression of the PTEN tumor suppressor gene in human hepatocellular cancer
Gastroenterology
(2007) - et al.
Bivariate analysis of sensitivity and specificity produces informative summary measures in diagnostic reviews
J. Clin. Epidemiol.
(2005) - et al.
Clinical practice guidelines: a manual for developing evidence-based guidelines to facilitate performance measurement and quality improvement
Otolaryngol. Head Neck Surg.
(2006) - et al.
MicroRNA-206 is associated with invasion and metastasis of lung cancer
Anat. Rec. (Hoboken)
(2011) Plasma specific miRNAs as predictive biomarkers for diagnosis and prognosis of glioma
J. Exp. Clin. Cancer Res.
(2012)
miR-21 plays a pivotal role in gastric cancer pathogenesis and progression
Lab. Invest.
MicroRNA-21 targets the tumor suppressor gene tropomyosin 1 (TPM1)
J. Biol. Chem.
Differential microRNAs expression in serum of patients with lung cancer, pulmonary tuberculosis, and pneumonia
Cell Biochem. Biophys.
Direct serum assay for microRNA-21 concentrations in early and advanced breast cancer
Clin. Chem.
Micromanagers of gene expression: the potentially widespread influence of metazoan microRNAs
Nat. Rev. Genet.
Serum miR-21 expression in human esophageal squamous cell carcinomas
Asian Pac. J. Cancer Prev.
MicroRNA signatures in human cancers
Nat. Rev. Cancer
Characterization of microRNAs in serum: a novel class of biomarkers for diagnosis of cancer and other diseases
Cell Res.
MicroRNA-378 is associated with non-small cell lung cancer brain metastasis by promoting cell migration, invasion and tumor angiogenesis
Med. Oncol.
Identification of ten serum microRNAs from a genome-wide serum microRNA expression profile as novel noninvasive biomarkers for nonsmall cell lung cancer diagnosis
Int. J. Cancer
Circulating plasma MiR-141 is a novel biomarker for metastatic colon cancer and predicts poor prognosis
PLoS One
Bias in meta-analysis detected by a simple, graphical test
BMJ
Micromarkers: miRNAs in cancer diagnosis and prognosis
Expert Rev. Mol. Diagn.
Measuring inconsistency in meta-analyses
BMJ
MicroRNAs in the miR-106b family regulate p21/CDKN1A and promote cell cycle progression
Mol. Cell. Biol.
Global cancer statistics
CA Cancer J. Clin.
Plasma miR-21: a potential diagnostic marker of colorectal cancer
Ann. Surg.
Circulating microRNAs in plasma of patients with oesophageal squamous cell carcinoma
Br. J. Cancer
Prognostic impact of circulating miR-21 and miR-375 in plasma of patients with esophageal squamous cell carcinoma
Expert Opin. Biol. Ther.
Prognostic impact of circulating miR-21 in the plasma of patients with gastric carcinoma
Anticancer Res.
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