Abstract
Objective. Recently, many studies have shown that microRNAs (miRNA) exhibit altered expression in various cancers and may play an important role as prognostic biomarker of cancers. We performed a meta-analysis to evaluate the impact of miR-375 expression in solid tumors on patients' overall survival (OS). Methods. Studies were identified by searching PubMed, Embace, and Cochrane Library (last search update was in May 2014) and were assessed by further quality evaluation. The pooled hazard ratios (HRs) with 95% confidence intervals (CIs) for total and stratified analyses were calculated to investigate the association between miR-375 expression and cancer patients OS. Results. Our analysis results indicated that downregulation of miR-375 predicted poor OS (HR = 1.91, 95% CI 1.48–2.45, P < 0.001). Subgroup analyses showed that lower expression of miR-375 was significantly related with poor OS in patients with esophageal carcinoma (HR = 2.24, 95% CI 1.69–2.96, P < 0.001) and non-small-cell lung cancer (NSCLC) (HR = 1.71, 95% CI 1.31–2.24, P < 0.001). Conclusions. The findings from this meta-analysis suggest that miR-375 expression is associated with OS of patients with malignant tumors and could be a useful clinical prognostic biomarker.
Highlights
Cancer is one of the most common causes of death worldwide and has become a major public health issue [1]
In the subgroup of tumor type, we found the downregulation of miR-375 was significantly associated with worse overall survival (OS) in esophageal carcinoma (HR = 2.24, 95% confidence intervals (CIs) 1.69–2.96; P < 0.001; fixed-effects model) and non-small-cell lung cancer (NSCLC) (HR = 1.71, 95% CI 1.31– 2.24; fixed-effects model), without any heterogeneity in the data (I2 = 1.9%, P = 0.415; I2 = 0.0%, P = 0.554, resp.) (Table 2 and Figure 3)
Genome-wide miRNA expression profiling studies revealed that miR-375 is widely present in various tissues and organs, and its expression is significantly aberrant in malignant tumors, such as head and neck squamous cell carcinoma (HNSCC), NSCLC, melanoma, glioma, hepatocellular, esophageal, gastric, breast, and prostate cancer [10,11,12,13,14,15,16, 19, 27]
Summary
Cancer is one of the most common causes of death worldwide and has become a major public health issue [1]. MicroRNAs (miRNAs), small noncoding RNAs with a length of approximate 22 nucleotides, have been demonstrated to have high potential prognostic value in many cancers. Catalyzed by the ribonuclease Drosha and its essential cofactor DGCR8, pri-miRNAs release a 60–80-nucleotide precursor (pre-miRNA) which is exported to cell cytoplasm and cleaved by Dicer to generate a 22-nucleotide duplex. The dysregulation of the biogenesis and function of miRNAs is often associated with human diseases, especially malignancies [4]. Accumulating evidence has demonstrated that miRNAs act as oncogenes or tumor suppressors by targeting genes involved in cell differentiation, proliferation, survival, apoptosis, and metastasis (reviewed in [5]). The expression of numerous miRNAs is dysregulated in various cancers, which is often associated with diagnosis, staging, progression, prognosis, and response to clinical therapies (reviewed in [6])
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