Abstract
Objective To assess the association between the expression level of miR-16 and prognosis of solid cancer patients by meta-analysis and bioinformatic analysis. Methods PubMed, Web of Science, and Embase databases were searched until October 31, 2019, to identify eligible studies reporting the association of the miR-16 status with the prognosis of solid cancer patients. Hazard ratios (HRs) with 95% confidence intervals (CIs) were pooled, and a heterogeneity test was conducted. Sensitivity analysis and a publication bias test were also carried out. Furthermore, the miRpower database was used to validate the association. Results Thirteen articles with 2303 solid cancer patients were included in the meta-analysis. Solid cancer patients with low expression level of miR-16 had shorter survival time (I2 = 84.0%, HR = 1.47, 95% CI: 1.13-1.91, P = 0.004). In the subgroup analyses of cancer sites, low miR-16 expression level was associated with poor prognosis in the reproductive system cancers (I2 = 33.3%, HR = 1.24, 95% CI: 1.06-1.45, P = 0.008). Sensitivity analysis suggested that the pooled HR was stable and omitting a single study did not change the significance of the pooled HR. Begg's test and Egger's test revealed no publication bias in the meta-analysis. In bioinformatic analysis, the significant association between miR-16 level and prognosis of patients with reproductive system cancers was further confirmed (HR = 1.21, 95% CI: 1.03-1.42, P = 0.017). Conclusion Low expression level of miR-16 is an indicator for poor prognosis of solid cancer patients, particularly in reproductive system cancers.
Highlights
MicroRNAs, a family of 21-25-nucleotide small noncoding RNAs, participate in a variety of pathophysiological processes, such as cell migration, invasion, proliferation, and differentiation [1]
The studies which met the following explicit criteria were included: (1) the study design was a prospective study, (2) the study population were patients who have been diagnosed with certain cancers by medical institutions, (3) miR-16 expression levels were classified as two categories, (4) hazard ratio (HR) and 95% confidence intervals (CIs) can be extracted directly or indirectly by calculation, (5) types of cancer are limited to solid cancer, and (6) language is limited to English
In the stratified analyses of cancer sites, low miR-16 expression level was associated with poor prognosis in the reproductive system cancers (I2 = 33:3%, HR = 1:24, 95% CI: 1.06-1.45, P = 0:008) and other system cancers (I2 = 63:5%, HR = 2:07, 95% CI: 1.38-3.10, P ≤ 0:001)
Summary
MicroRNAs (miRNAs), a family of 21-25-nucleotide small noncoding RNAs, participate in a variety of pathophysiological processes, such as cell migration, invasion, proliferation, and differentiation [1]. They regulate gene expression and function as oncogenes or tumor suppressors posttranscriptionally by degrading target miRNAs or blocking their translation [2]. Dysregulated expression of miRNAs could result in solid cancer progression and might serve as an independent predictor for solid patient outcomes [8]. MiR125b was an independent prognostic marker for lung cancer [9], and miR-221 was a predictor of prognosis of patients with hepatocellular carcinoma [10]. A systematic review and meta-analysis came to the conclusion that miR-16 family
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